Artigos de revistas sobre o tema "Inc National Cargo Bureau"

Background:ObjectivesThe objective of this study is to report long-term, end-of-study-program safety outcomes, relating to major adverse cardiovascular events (MACE), in adult patients with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (AxSpA) who received ≥1 dose of Ixekizumab (IXE) over 5 years (PsO) or 3 years (PsA, axSpA).MethodsThe incidence of MACE was assessed across 25 randomized clinical trials (17 PsO, 4 PsA, 4 axSpA) examining long-term safety of IXE. MACE rates were analyzed for pooled studies by years of therapy, through March 2022. Exposure-adjusted incidence rates (IRs) per 100 patient-years, at successive year intervals are reported.ResultsThe incidence of MACE was low among patients with PsO (IR=0.5), PsA (IR=0.5), and axSpA (IR=0.3). In the PsO cohort, of the 103 reported MACE cases, 20 were fatal (19.4%), 57 recovered (55.3%), and 17 recovered with sequelae (16.5%). Of the 12 reported MACE cases in the PsA cohort, 2 were fatal (16.7%), 9 recovered (75.0%), and 1 recovered with sequelae (8.3%). All 6 MACE cases reported in the axSpA cohort recovered (100.0%).IRs were low and stable over the treatment periods. The most common types of MACE reported in the PsO, PsA and axSpA cohorts were non-fatal myocardial infarction (PsO: IR= 0.3; PsA: IR=0.3; axSpA: IR=0.3), nonfatal stroke (PsO: IR=0.1; PsA: IR=0.2) and vascular death (PsO: IR=0.1; PsA: IR=0.1). All MACE cases were confirmed by adjudication.ConclusionThe incidence of MACE was low and stable over the IXE treatment periods examined.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsMark Lebwohl Consultant of: Arcutis, Boehringer Ingelheim, Bristol Myers.Squibb, Verrica, AbbVie, Amgen, Eli Lilly, Janssen, Ortho Dermatologics, Pfizer, UCB Pharma,Avotres Therapeutics, AnaptysBio, Aristea Therapeutics, BioMX, Cara Therapeutics, Castle Biosciences, Dermavant, Evommune, Facilitatation of International Dermatology Education, Forte.Biosciences, Foundation for Research and Education in Dermatology, Hexima, Meiji Seika Pharma, Mindera Health, Regeneron, Seanergy, Incyte, Arrive Technologies, Dr Reddy’s Laboratories, Evelo Biosciences, Helsinn Therapeutics, LEO Pharma, Mount Sinai, CorEvitas (formerly Corrona), Grant/research support from: Abbvie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara.Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development,LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc., Atul Deodhar Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, UCB Pharma, Aurinia, Moonlake, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Glaxo Smith & Kline, Janssen, Novartis, Pfizer, UCB, Sergio Schwartzman Speakers bureau: AbbVie, Janssen, Lilly, Pfizer, Novartis, UCB, Consultant of: AbbVie,Janssen, Eli Lilly and Company, Pfizer, Novartis, UCB, Myriad, Regeneron, Sanofi, Stelexis, Jubilant, Teijin, National Psoriasis Foundation Medical Boar, Grant/research support from: Lilly, Carlo Salvarani Consultant of: AbbVie, Eli Lilly and Company, and Roche, Grant/research support from: Roche, Meghan Feely Shareholder of: Eli Lilly and Company, Speakers bureau: Mount Sinai, Consultant of: Mount Sinai, Hospital, NY, Eli Lilly and Company, Aerolase, Castle Biosciences, Galderma Aesthetics, Revian, Sonoma Pharmaceuticals, Suneva Medical, and Sun Pharmaceutical Industries, AAD Investment Committee, AAD Media Expert Team, AEI Leadership Network, Leonine Forum, WDS Committees: Practice Advisory, Finance and Investment, Fundraising and Philanthropic Activities, Prevention Medical Review Board, ASDS Social Media Ambassador, Grant/research support from: Eli Lilly and Company, Mount Sinai, MC Medical Group, The Dermatology and Laser Group, Windsor Dermatology, Employee of: Eli Lilly and Company, Danting Zhu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Proton Rahman Consultant of: AbbVie, Eli Lilly and Company, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis, Kim Papp Speakers bureau: AbbVie, Amgen, Bausch Health/Valeant, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kyowa Hakko Kirin, Leo, Merck,Novartis, Pfizer, Sanofi, Consultant of: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen,Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv.Therapeutics, Xencor, Grant/research support from: AbbVie, Acelyrin, Akros, Amgen, Anacor, Aralez Pharmaceuticals, Arcutis, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals,Dow Pharma, Eli Lilly, Evelo, Forbion, Galderma, Gilead, GSK, Incyte, Janssen,Kyowa Hakko Kirin, Leo, Meiji Seika Pharma, Merck (MSD), Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Reistone, Roche, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv.Therapeutics, Xencor, Joseph F. Merola Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Janssen, LEO Pharma, Novartis, Pfizer, Sanofi Regeneron, Sun Pharma, and UCB Pharma, Alice B Gottlieb Shareholder of: Xbiotech (stock options for an RA project), Consultant of: Amgen, AnaptysBio, Avotres Therapeutics, Boehringer.Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi, Sun Pharma, UCB Pharma, and Xbiotech, Grant/research support from: AnaptysBio, Janssen, Novartis, Ortho Dermatologics, Sun Pharma, BMS, and UCB Pharma, Andrew Blauvelt Speakers bureau: AbbVie, UCB, Consultant of: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB Pharma, EcoR1, Vibliome, Grant/research support from: AbbVie, Acelyrin, Amgen, Arcutis, Athenex, Boehringer Ingelheim,Bristol-Myers Squibb, Dermavant, Evelo, Galderma, Incyte, Janssen, Leo, Merck, Novartis, Pfizer, Regeneron, Sun Pharma, and UCB Pharma Investigator (payments made to my company),

Background:Patients (pts) with rheumatoid arthritis (RA) have an increased risk of some malignancies vs the general population, and this can vary by region/race.1,2 Data on the epidemiology and impact of biological (b)DMARDs and targeted synthetic (ts)DMARDs, such as Janus kinase (JAK) inhibitors, on the incidence of malignancies in Japanese pts with RA are limited. The National Database of Rheumatic Diseases in Japan (NinJa) is one of the largest RA registries in Japan.Objectives:To evaluate the incidence of malignancies in Japanese pts with RA using NinJa registry data.Methods:This retrospective observational study analysed NinJa registry data for Japanese pts with RA aged ≥18 years with ≥1 data entry between 2013 (first JAK inhibitor approval for RA in Japan) and 2018. The overall cohort included all pts with RA, and two sub-cohorts were analysed: pts exposed and unexposed to bDMARDs (exposure defined as ≥1 bDMARD reported in database). Crude incidence rates (IRs) for malignancies (including non-melanoma skin cancer) were calculated as the number of events per 100 pt-years of follow-up (time between start of follow-up or the date of first bDMARD exposure [for bDMARD-exposed pts] and end of observation period, or withdrawal from database). The most recent data for incidence of malignancy in the Japanese general population (2013–2017 data from the National Cancer Center, Japan) were used to calculate standardised incidence ratios (SIRs) and age- and sex-adjusted standardised rates (ASRs) for malignancies. Cross-sectional (per calendar year) and cumulative analyses were performed for the overall cohort. Cumulative rates were calculated for sub-cohorts, and all cumulative analyses were repeated excluding pts exposed to JAK inhibitors (ie ≥1 JAK inhibitor reported in database).Results:Data were collected for 26 607 Japanese pts with RA from 2013–2018. In the cross-sectional analysis (Table 1), the SIR and ASR for malignancies in all pts with RA were generally consistent from 2013–2018. In the cumulative analysis, the SIR (95% CI) for malignancies from 2013–2018 was 0.97 (0.91, 1.03) in all pts with RA, and 0.93 (0.82, 1.04) and 0.99 (0.92, 1.07) in pts exposed and unexposed to bDMARDs, respectively (Figure 1). Adjusting for age/sex, the cumulative ASR (95% CI) for malignancies from 2013–2018 was 0.83 (0.76, 0.90) in all pts with RA, and 0.82 (0.69, 0.95) and 0.86 (0.77, 0.96) in pts exposed and unexposed to bDMARDs, respectively (Figure 1). In all cohorts, the cumulative SIR and ASR were similar when pts exposed to JAK inhibitors were excluded (Figure 1).Table 1.Cross-sectional analysis of the incidence of malignancies in Japanese pts with RA from 2013–2018All RA2013 (N=13 423)2014 (N=15 584)2015 (N=15 751)2016 (N=16 107)2017 (N=15 994)2018(N=15 003)Total follow-up, PY13 35314 86614 82914 97014 74814 898Pts with events, n140164174168161211Crude IRa(95% CI)1.05(0.89, 1.24)1.10(0.95, 1.29)1.17(1.01, 1.36)1.12(0.97, 1.31)1.09(0.94, 1.27)1.42(1.24, 1.62)ASRa,b(95% CI)0.76(0.60, 0.93)0.76(0.62, 0.90)0.90(0.68, 1.11)0.88(0.68, 1.07)0.80(0.62, 0.98)0.88(0.74, 1.01)SIRb(95% CI)0.97(0.82, 1.14)1.01(0.86, 1.17)1.02(0.87, 1.18)0.88(0.75, 1.02)0.86(0.73, 1.00)1.10(0.95, 1.25)aIR/ASR were calculated as number of events per 100 PY of follow-upbData from a Japanese general population database of malignancy incidence from 2013–2017, provided by the Center for Cancer Control and Information Services, National Cancer Center, JapanPY, pt-yearsConclusion:The incidence of malignancies in Japanese pts with RA, registered in the NinJa database from 2013–2018, was similar to that in the Japanese general population. The SIR and ASR for malignancies were comparable in pts exposed and unexposed to bDMARDs. In all cohorts, rates did not increase when pts exposed to JAK inhibitors were included.References:[1] Dougados et al. Ann Rheum Dis 2014; 73: 62-68.[2] Parikh-Patel et al. Cancer Causes Control 2009; 20: 1001-1010.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Christina Viegelmann, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Toshihiro Matsui Speakers bureau: Astellas, Ayumi, Chugai, Daiichi-Sankyo, Eli Lilly, Ono, Pfizer Inc, Takeda, Tanabe-Mitsubishi, Consultant of: Pfizer Inc, Grant/research support from: Chugai, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shigeyuki Toyoizumi Employee of: Pfizer R&D Japan, Fujio Matsuyama Consultant of: Pfizer Inc, Employee of: CRECON Medical Assessment Inc, Tatsunori Murata Consultant of: Pfizer Inc, Employee of: CRECON Medical Assessment Inc, Yukitomo Urata Speakers bureau: Asahi Kasei, Chugai, Eli Lilly, Pfizer Inc, Consultant of: AbbVie, Asahi Kasei, Chugai, Pfizer Inc, Kimito Kawahata Speakers bureau: Pfizer Inc, Consultant of: Pfizer Inc, Grant/research support from: Pfizer Inc, Shigeto Tohma Speakers bureau: Astellas, Ayumi, Chugai, Ono, Pfizer Inc, Takeda, Consultant of: Pfizer Inc

Abstract INTRODUCTION: Despite proteasome inhibitors (PIs) improving multiple MM (MM) outcomes, patients often become resistant. Identifying mechanisms of resistance with translational potential are an urgent unmet clinical need. Preliminary studies from our group have identified that the therapeutically targetable acid ceramidase, ASAH1, is a key mediator of PI resistance and its presence in extracellular vesicles (EVs) derived from resistant MM cells, confers PI resistance on drug naïve MM cells. METHODS: Nanosight technology, transmission electron microscopy and immunoblot were used to define EVs. Viability and apoptosis assays were used to determine the effects of EVs and inhibitors on resistance acquisition/sensitization to PIs. LC-MS was used to interrogate EV cargo contents. Clinical relevance of ASAH1 was determined in multiple human data cohorts (M2GEN and MMRF CoMMpass). Genetic (shRNA) and pharmacological (ceranib-2) approaches were used to assess the role of ASAH1 mechanistically in vitro and in vivo using multiple isogenic naïve and PI resistant cell lines, patient derived CD138+ MM cells and NSG mouse models. RESULTS: Co-culture of sensitive MM cells with resistant MM-EVs alone significantly protected against PI cytotoxicity. Proteomic profiling revealed high levels of ASAH1 in EVs derived from PI resistant MM cells. Further, we observed ASAH1 is abundant in lysates of multiple PI resistant cell lines compared to their isogenic drug sensitive counterparts. In human datasets, high ASAH1 expression was noted in PI resistant MM patients compared to those newly diagnosed and correlated with significantly shorter survival times. Mechanistically, knockdown of ASAH1 led to reduced conversion of ceramide to sphingosine 1-phosphate (S1-P) and decreased expression/activity of the anti-apoptotic proteins MCL-1, BCL2 and BCL-xL and increases in pro-apoptotic BIM and NOXA. Notably, ASAH1 knockdown also significantly sensitized the cells to PI treatment and this effect was rescued by addition of exogenous S1-P. Pharmacological inhibition of ASAH1 with ceranib-2 also sensitized resistant cells to PI treatment and prevented EV mediated resistance transfer in vitro. This was recapitulated ex vivo with human clinical samples. Our orthotopic in vivo model using PI-resistant U266-PSR cells show that ceranib-2 is highly effective in limiting the growth of PI-resistant disease, protecting against MM induced bone disease, and increasing overall survival compared to both bortezomib and vehicle controls. CONCLUSION: We define the ceramidase ASAH1 as a novel, druggable target for the treatment of PI resistant MM. Disclosures Hampton: M2Gen: Current Employment. Siqueira Silva: AbbVie Inc.: Research Funding; Karyopharm Therapeutics Inc.: Research Funding. Shain: Janssen oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi Genzyme: Consultancy, Speakers Bureau; Karyopharm Therapeutics Inc.: Honoraria, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; GlaxoSmithLine, LLC: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Adaptive Biotechnologies Corporation: Consultancy, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a viable treatment option for many cancers but its clinical utility is limited due to the occurrence of graft-versus-host disease (GVHD). Understanding the impact of obesity on immune function has become increasingly important in the setting of the current obesity pandemic. We report here that obesity has a negative and selective impact on acute gut GVHD. Diet-induced obese (DIO) mice exhibited increased gut permeability, endotoxin translocation and radiation-induced gastrointestinal damage. After allo-HSCT, DIO recipients across strains and sex had markedly increased pro-inflammatory cytokines (IL-6, TNF), GVHD biomarker ST2, MHC class II expression and exhibited rapid mortality associated with severe acute gut pathology. This obesity-associated lethal acute gut GVHD was dependent on donor CD4 T cells and occurred even in minor MHC mismatch strain combination in which only a delayed skin chronic GVHD resulted in lean recipients. Pro-inflammatory cytokine blockade targeting both IL-6 and TNF ameliorated obesity-associated acute gut GVHD while maintaining graft-versus-tumor (GVT) effects. Microbiome assessment of DIO mice revealed markedly reduced microbiome diversity and decreased Clostridiaceae abundance. Additionally, DIO mice had a significant increase of GVHD-associated Akkermansia muciniphila before and after allo-HSCT compared to the controls. Extended antibiotic treatment of DIO mice protected from the endotoxin translocation, cytokine storm as well as gut GVHD pathology but did not protect later development of chronic skin GVHD. These results demonstrate that obesity alters the microbiome and imparts differential effects on GVHD following allo-HSCT with decreased survival and this inferior outcome can be pre-empted by combined pro-inflammatory cytokine blockade or antibiotic pretreatment. Disclosures Pai: Roche-Genentech: Employment. Holtan:CSL Behring: Consultancy; Incyte: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy. Ferrara:ViraCor: Consultancy; Incyte: Consultancy; Kamada: Consultancy; Mallinckrodt: Consultancy; Enlivex: Consultancy; Xenikos: Consultancy; CSL Behring: Consultancy; National Institutes of Health: Research Funding. Levine:Novartis: Honoraria; Kamada: Research Funding; bluebird bio: Consultancy; National Cancer Institute: Research Funding; Incyte: Consultancy, Research Funding; Ironwood: Honoraria; Biogen: Other: non-financial support; Viracor: Patents & Royalties: biomarker patent. Abedi:Abbie: Speakers Bureau; Gilead: Speakers Bureau; Celgene: Speakers Bureau; BMS: Speakers Bureau; Takeda: Speakers Bureau. Blazar:Kamon Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Five Prime Therapeutics Inc: Co-Founder, Membership on an entity's Board of Directors or advisory committees; Regeneron Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics and BlueRock Therapeuetics: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics, Inc.: Research Funding; RXi Pharmaceuticals: Research Funding; Alpine Immune Sciences, Inc.: Research Funding; Abbvie Inc: Research Funding; Leukemia and Lymphoma Society: Research Funding; Childrens' Cancer Research Fund: Research Funding; KidsFirst Fund: Research Funding; Tmunity: Other: Co-Founder; BlueRock Therapeutics: Membership on an entity's Board of Directors or advisory committees.

This paper selects the relevant data of 30 years from 1989 to 2018 from the National Bureau of Statistics. This paper selects the gross national income as the focus variable, and the number of business outlets, cargo transportation volume, investment in fixed assets and the total population of the country as the control variables to make an empirical analysis on the influencing factors of express delivery volume in China. EVIEWS software is used to estimate, test and correct the parameters of the model. The economic significance of the final results is analyzed, and then the research conclusion is drawn and the existing deficiencies are summarized.

Abstract Introduction: There are some treatment options for lower risk myelodysplastic syndromes (MDS) such as erythropoiesis-stimulating agents (ESAs), anabolic steroids, hypomethylating agents, and immunosuppressants. The object of this multicenter retrospective study was to survey the current situation about treatment selection and the prognosis of the lower risk MDS cases in Japan. We also evaluated the prognosis of the cases with paroxysmal nocturnal hemoglobinuria (PNH) type cells and therapeutic effects of cyclosporine. Methods: We investigated the clinical information in the form of a questionnaire for joint research facilities as to each case of newly diagnosed MDS between 2013 and 2018 corresponding to the lower risk of International Prognostic Scoring System (IPSS) or revised IPSS (IPSS-R). The diagnosis of MDS was based on WHO 2008 or WHO 2016 classification. Survival analysis was conducted using Kaplan-Meier method and log-rank test. Multivariate analysis was performed using Cox proportional hazard regression model. This study was approved by the institutional review board of the University of Tokyo and other research facilities. This work was supported by the Research Program of Intractable Disease (the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes) provided by the Ministry of Health, Labor, and Welfare of Japan. Results: 1,304 cases at thirty facilities nationwide were enrolled. Median age was 76 years [IQR, 68 - 83], and male and female ratio was 61.3% and 38.7%. At diagnosis, 19.0% and 4.4% of the cases were dependent on red blood cells and platelets transfusion, respectively. The risk classification of enrolled cases was as follows: very low, 217 (16.6%); low, 652 (50.0%); intermediate, 360 (27.6%); high, 56 (4.3%); very high, 4 (0.3%); not determined, 14 (1.1%). 1,230 cases of the very low, low and intermediate risk groups were included in subsequent analyzes. Serum erythropoietin levels were measured in 466 cases (37.9%) with a median of 61.8 IU/l, and 74.2% and 85.7% cases showed less than 200 IU/l and 500 IU/l, respectively. PNH type cells in the peripheral blood were evaluated in 231 cases and were positive in 33 cases (14.3%). Median follow-up period was 22 months. As an initial therapy, 26.4% and 11.6% of transfusion-dependent and independent cases started to receive ESAs, respectively. 16.6% and 11.5% took oral anabolic hormones, and azacytidine were administered to 17.0% and 7.2% of each group. 55.4% of transfusion-independent cases were just followed up at first. Median overall and acute myeloid leukemia (AML)-free survival was 70.0 months [95% CI, 61.0 - not reached] and 62.0 months [95% CI, 54.0 - 74.0], respectively. Log-rank analysis revealed significant differences among IPSS-R risk groups about overall and AML-free survival (p<0.01 and p<0.01, respectively). Multivariate analysis confirmed that initiating azacytidine at the time of diagnosis conferred an independent significant poor prognostic factor with respect to overall survival (hazard ratio for death, 1.74; p<0.01) and AML-free survival (hazard ratio for death or onset of AML, 1.86; p<0.01) in addition to sex, age, IPSS-R classification, and transfusion-dependency. Comparing thirty-three positive cases of PNH type cells with 198 negative cases, overall and AML-free survival was significantly better in the former group (p<0.01 and p<0.01, respectively). Median overall and AML-free survival were not reached in the positive group and 51.0 months [95% CI, 47.0 - 79.0] and 49.1 months [95% CI, 40.0 - 57.1] in the negative group, respectively. Interestingly, focused on the positive cases, 14 cases receiving cyclosporine revealed better AML-free survival than the others (p=0.033). Overall survival was tended to be better (p=0.052). On the other hand, cyclosporine did not improve the prognosis of the PNH type cells negative cases. It is thought to be consistent with the effectiveness of immunosuppressive therapy in aplastic anemia with PNH type cells. Conclusion: ESAs, anabolic steroids, and azacytidine were frequently selected as an initial treatment for lower risk MDS cases in Japan, however, when to start azacytidine is an issue for consideration. Good response to cyclosporine may be obtained in cases with PNH type cells. Disclosures Masamoto: Eisai Co., Ltd.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; AbbVie GK: Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; SymBio Pharmaceuticals: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; MSD K.K.: Speakers Bureau. Miyazaki: Kyowa-Kirin: Honoraria; Sumitomo-Dainippon: Honoraria, Research Funding; Abbvie: Honoraria; Novartis: Honoraria; Nippon-Shinyaku: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Astellas: Honoraria; Janssen: Honoraria; Eisai: Honoraria; Daiichi-Sankyo: Honoraria; Chugai: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Mitani: Nippon Shinyaku Co.: Research Funding, Speakers Bureau; MSD Pharma.: Research Funding, Speakers Bureau; Novartis: Speakers Bureau; Pfizer Inc.: Speakers Bureau; Celgene Co.: Speakers Bureau; Takeda Pharma.: Research Funding, Speakers Bureau; Kyowa Kirin,: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Shire plc: Speakers Bureau; BML Inc: Speakers Bureau; Mochida Parma.: Speakers Bureau; Alexion Pharma.: Speakers Bureau; AbbVie Inc.: Speakers Bureau; Ono Pharma.: Speakers Bureau; Chugai Pharma.: Research Funding; Teijin Pharma.: Research Funding; Sumitomo Dainippon Pharma: Research Funding; Taiho Phama.: Research Funding; Otsuka Pharma.: Research Funding. Kurokawa: Sumitomo Dainippon Pharma Co., Ltd.: Research Funding, Speakers Bureau; AbbVie GK: Research Funding, Speakers Bureau; Teijin Limited: Research Funding, Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Daiichi Sankyo Company.: Research Funding, Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding, Speakers Bureau; MSD K.K.: Research Funding, Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Research Funding, Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau.

The study assessed the performance of public sector funded infrastructure in Nigeria, with a special focus on airports. It utilized secondary data obtained from the Federal Airports Authority of Nigeria (FAAN), the Nigerian Civil Aviation Authority (NCAA), and the National Bureau of Statistics (NBS) covering the period 2004 to 2016. A simple regression analyses of the data were carried out using total number of employees as the predictor variable and the total aircraft movement, total passenger movement, and total cargo movement as the dependent variables. The results of the analyses show that the p values calculated were < 0.05 alpha value, implying existence of a statistical relationship among the dependent variables (aircraft movement, passenger throughput, and cargo throughput) and independent variable (number of employees). Furthermore, the time series graphs show fluctuations in growth of the outputs (passenger throughput, aircraft movement and cargo throughput) for the Nigerian air transport system at various periods. This study has shown that there is a need for the government and stakeholders to take immediate actions in tackling factors responsible for the decline and fluctuations in the air transport industry.

The study investigated the relationships between the poverty level in Nigeria and levels of global and local pirate attacks against ships on one hand; and between the unemployment rate in Nigeria and the level of local and global attack against ships, as well as the volume of cargo pilfered from Nigerian ports, on the other hand. The study employed secondary data sourced from the Nigerian Ports Authority, the National Bureau for Statistics (NBS), and the International Maritime Bureau (IMB) on the poverty rate, unemployment rate, levels of pirate attacks against ships in local and global waters, and volume of cargo pilferages in ports. The multiple regression analysis method was used to analyze the dataset obtained, using poverty rate and unemployment rate as the dependent variables in each case. It was found that poverty among dwellers is a component driver of maritime piracy and sea robbery against ships trading in Nigeria, since there is a significant relationship between the level of maritime insecurity and the rate of poverty in Nigeria. The study also found that there is a significant relationship between the level of maritime piracy/sea robbery and the unemployment rate in Nigeria. Highlights Maritime insecurity in Nigeria waterways Pirate attacks against ships trading in Nigeria waters is linked to unrest in the Niger Delta region of Nigeria Maritime piracy in Nigeria waters is correlated with Poverty, unemployment, economic hardship in Nigeria Significant relationship exist between maritime insecurity and poverty rate in Nigeria

Background: Improved therapeutic strategies for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL) remain an unmet need. Venetoclax (Ven), a potent, highly selective, oral B-cell lymphoma 2 (BCL-2) inhibitor, and navitoclax (Nav), an oral BCL-2, BCL-XL, and BCL-W inhibitor, directly bind their BCL-2 family member targets to promote apoptosis. Ven and Nav have shown synergistic antileukemic effects in ALL preclinical models, suggesting dependence on BCL-2 family members. The addition of Ven to low-dose Nav may potentiate efficacy without the dose-limiting thrombocytopenia associated with Nav monotherapy (J Clin Oncol. 2012;30:488). Ven in combination with Nav and chemotherapy are under investigation in a Phase 1, multicenter, open-label, dose-escalation study in patients with R/R ALL and LL (NCT03181126). The results of a previous report on the overall study population (adult and pediatric patients) showed the triplet combination was well tolerated, with promising response rates observed (Jabbour, et al. EHA 2020. Abstract 2389). For the first time, reported here are safety, tolerability, pharmacokinetics, and antitumor activity of Ven with Nav and chemotherapy among the pediatric patients treated in that Phase 1 study. Methods: Eligible pediatric patients (aged ≥4-&lt;18 years and weight ≥20 kg) with R/R ALL and LL were enrolled to receive 400 mg Ven (weight-adjusted equivalent) daily. Nav was administered daily at 3 dose levels (25, 50, 100 mg) for patients weighing ≥45 kg and 2 dose levels (25, 50 mg) for patients weighing &lt;45 kg. Dose escalation decisions were guided by Bayesian optimal interval design. Patients could receive chemotherapy (PEG-asparaginase, vincristine, and dexamethasone) at the investigator's discretion. Primary outcome measures included safety assessments and pharmacokinetics. Secondary outcome measures included efficacy assessments. Exploratory biomarker assessments included evaluation of minimal residual disease (MRD). A safety expansion cohort assessed a discontinuous dosing schedule, 21 days on and 7 days off, of Ven with 50 mg Nav (25 mg for patients weighing &lt;45 kg). Results: As of June 23, 2020, 18 pediatric patients (pts) have enrolled (12 in dose-escalation; 6 in safety expansion); 13, 3, and 2 pts had B-ALL, T-ALL, and LL, respectively. Among pts in the dose-escalation phase, 6 received 25 mg Nav and 6 received 50 mg. Median age was 10 years (range, 6-16 years), 56% of pts were male, and the median number of prior therapies was 2 (range, 1-6). Median time on study was 10.4 months. All pediatric pts experienced treatment-emergent adverse events (TEAEs), and the most common were febrile neutropenia (50%), vomiting (44%), hyperglycemia (39%), and hypokalemia (39%). Grade 3/4 TEAEs occurred in 89% of pediatric pts, and the most common were febrile neutropenia (50%), neutropenia (33%), thrombocytopenia (33%), and anemia (28%). The only Grade 3/4 nonhematologic TEAEs related to Ven or Nav that occurred in &gt;1 pediatric pt were alanine aminotransferase increased (n=2) and vomiting (n=2). Of 8 dose-limiting toxicities (DLTs), 2 occurred in pediatric pts. The 2 DLTs included delayed count recovery (25 mg Nav) and sepsis (50 mg Nav, occurred after database lock). No pediatric pts experienced tumor lysis syndrome. No Grade 5 TEAEs occurred in pediatric pts; 8 pediatric pts (44%) died from disease progression. Ten pediatric pts (56%) achieved complete response (CR)/CR incomplete recovery (CRi)/CR without platelet recovery (CRp); 7 pts (39%) achieved undetectable MRD. Median overall survival was 11.4 months (95% CI, 2.9 months-not estimable). Eight pts (44%) proceeded to transplantation (n=5) or CAR T-cell therapy (n=3; cells harvested before start of study; Figure). Weight-based dosing of Ven and Nav achieved comparable exposures in pediatric pts. Exploratory correlative biomarker analyses, including BH3 profiling and genomic analyses, are underway and will be presented. Conclusion: In this Phase 1 study, Ven with Nav and chemotherapy was well tolerated and had promising efficacy in heavily pretreated pediatric patients with ALL and LL. Given that there were four DLTs with 100 mg Nav without evidence of increased efficacy, the recommended Phase 2 dose for adult and pediatric patients is 400 mg Ven with 50 mg Nav for patients weighing ≥45 kg and 25 mg Nav for patients weighing &lt;45 kg. Figure Disclosures Rubnitz: AbbVie Inc.: Research Funding. Alexander:Abbvie, Inc.: Other: Travel Support. Laetsch:Bayer: Consultancy, Research Funding; Cellectis: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Research Funding. Khaw:Amgen: Other: Travel Support, Research Funding; Novartis: Other: Travel Support; AbbVie, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Jazz Pharmaceuticals: Research Funding; Walter and Eliza Hall Institute of Medical Research: Patents & Royalties: recipient of a share in royalty payments . Pullarkat:Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Opferman:St. Jude Children's Research Hospital: Current Employment; AbbVie, Inc.: Research Funding; National Institutes of Health: Research Funding. Rosenwinkel:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Tong:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Pesko:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Badawi:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Vishwamitra:AbbVie, Inc.: Current Employment, Other: may hold stock or other options. Kim:AbbVie, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Other: may hold stock or other options. Mullighan:Illumina: Consultancy, Honoraria, Speakers Bureau; AbbVie, Inc.: Research Funding; Pfizer: Honoraria, Research Funding, Speakers Bureau. OffLabel Disclosure: Yes, venetoclax is a BCL-2 inhibitor that is FDA approved for some indications. Venetoclax for treatment of acute lymphoblastic leukemia is not an approved indication.

Abstract Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the world and has a median age at diagnosis in the seventh decade. FL in young adults (YA; 40 years old or younger) is extremely rare. Currently, there are no standard approaches guiding treatment of YA patients with FL, and very little is known about disease characteristics and outcomes of YA patients with FL given limited research conducted in this vulnerable population. To gain further insight into FL in YA, we analyzed the National LymphoCare Study (NLCS) to describe disease and patient characteristics, as well as features of treatment in YA patients with FL. We previously reported that 2-year progression-free survival (PFS) is an important survival endpoint in patients with FL undergoing chemo-immunotherapy. Hence, we also sought to characterize 2-year PFS in this age group and compare it to older cohorts. Methods: Evaluablepatients were identified in the NLCS, and those between 18–40 years of age with newly diagnosed FL at any stage were classified as YA patients. Patients with mixed histology or transformed disease were excluded, as were patients with progression of disease prior to beginning first-line treatment. Survival probability was estimated by the Kaplan-Meier method. We estimated the association of age group with PFS using hazard ratios (HR) and 95% confidence intervals (CI) from multivariable Cox models. Results: A total of164 YA patients with FL were analyzed, representing 6.2% of the NLCS population, similar to the observed frequency in the Surveillance, Epidemiology, and End Results (SEER) Program data (4.8% of all FL). Sixty nine percent of YA patients had advanced stage disease. The majority of patients (80%) had low-grade histology, and 50% had good risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent of patients (31/164) underwent watchful waiting, 12% received rituximab monotherapy, and 47% received chemo-immunotherapy (61% of whom received R-CHOP [rituximab, doxorubicin, vincristine, prednisone]). There was no significant difference in FLIPI score or other baseline disease characteristics compared to adult patients aged 41–60 years. Eleven deaths occurred among YA with FL; only 5 of these were lymphoma related. Overall survival (OS) at 2 years was 97.4% (95% CI 93.3%, 99.0%), and at 5 years, 93.7% (88.3%, 96.7%), which was similar to patients aged 41–60 (97.2% [96.0%, 98.0%] at 2 years, and 92.0% [90.1%, 93.5%] at 5 years). After a median follow-up of 7.1 years, OS in YA FL was 92%. Through follow-up, there were 64 PFS events. The estimated 2-year PFS (95% CI) for YA and adults 41–60 was 75.9% (67.1%, 82.6%) and 80.9% (78.1%, 83.4%), respectively. After adjusting for FLIPI score, there was no difference in PFS for YA with FL requiring first-line treatment (excluding watchful waiting) compared to adults aged 41–60 years (HR=0.93; 95% CI 0.69, 1.25), and no difference in OS compared to adults aged 41–60 years (HR=1.19; 95% CI 0.64, 2.23). Conclusions: In the largest cohort of YA patients with FL to date, we found few differences in outcomes compared to patients aged 41–60. FLIPI and other disease characteristics were similar to adults aged 41–60 years. There were no differences between YA FL and adults aged 41–60 in PFS for all treated patients. OS in the YA group of patients with FL was outstanding. YA patients with FL have reassuringly similar outcomes to patients aged 41–60. Fertility preservation and survivorship issues should be taken into consideration when defining management strategies, but otherwise these data support that YA patients with FL should not be approached differently from older adults with the same disease. Disclosures Byrtek: Genentech, Inc.: Employment, Equity Ownership. Dawson:Genentech, Inc.: Employment, Equity Ownership. Zhou:RTI-HS: Employee of RTI-HS, which has research contracts with Genentech Other. Flowers:Seattle Genetics: Consultancy; Spectrum: Consultancy, Research Funding; Sanofi: Research Funding; Abbott: Research Funding; Novartis: Research Funding; OptumRx: Consultancy; Millennium/Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Allos: Consultancy. Farber:Gilead: Speakers Bureau; Janssen/Pharmacyclics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Leukemia Lymphoma Society NJ Chapter: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Speakers Bureau, Stock ownership Other. Cerhan:Genentech, Inc.: LymphoCare Scientific Advisory Board Other. Link:Genentech, Inc.: Consultancy, Scientific Advisory Board for Genentech Other.

Abstract Introduction: Patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) who cannot tolerate or who are not eligible for autologous or chimeric antigen receptor T cell (CAR-T) therapy have limited therapeutic options and suboptimal long-term outcomes. In patients who were not eligible for HSCT, the rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) regimen (and variations using methylprednisolone or carboplatin/oxaliplatin) have shown an overall response rates (ORR) of ~50%, a complete response (CR) rate of ~25% (Gopal, Leuk Lymphoma, 2010), and a median progression-free survival (PFS) and an overall survival (OS) of 3 and 9 months, respectively (Crump, Hematol Oncol Clin N Am. 2016; Gopal Leuk Lymphoma, 2010; Ng, Br J Cancer, 2005; Sirohi, Hematology, 2007; Barton, Eur J Haematol. 2015; Moccia Leuk Lymphoma, 2017). Selinexor is an oral small molecule selective inhibitor of exportin-1 (XPO1) mediated nuclear export (SINE) compound leading to activation of tumor suppressor proteins and reduction in oncoprotein levels. It also reduces the expression of deoxyribonucleic acid (DNA) damage repair proteins and therefore potentiates DNA damage-based therapies leading to an increased death of cancer cells. Selinexor has synergistic effects with gemcitabine and cisplatin, and enhanced anti-lymphoma effects with dexamethasone. In the SADAL study (n=134), single-agent oral selinexor 60 mg twice weekly induced an ORR of 29% and a CR rate of 13% in patients with RR DLBCL. The response rates were consistent across various subgroups including patients &lt;70 vs ≥70 years old, those with de novo and transformed DLBCL, and GCB and non-GCB subtypes of DLBCL. The median duration of response (DOR) was 9.3 months, and 23 months for patients who achieved CR. OS was 9.0 months. In June 2020, selinexor monotherapy was approved in the US for the treatment of adult patients with RR DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor in combination with R-GDP was evaluated in a Phase 1 clinical trial (SELINDA), in which patients with DLBCL received either 40 or 60 mg selinexor once or twice weekly in combination with standard dose R-GDP. The recommended phase 2 dose for further exploration was 40 or 60 mg once weekly with an ORR of 60-80%. Therefore, combining selinexor with R-GDP is expected to improve response rates, and continuation of treatment with single-agent selinexor is expected to prolong the duration of responses, improve PFS (and potentially OS) in patients with RR DLBCL. Materials and methods: XPORT-DLBCL-030 is a Phase 2/3, multicenter study. The Phase 2 portion of the study is an open-label randomized study to identify the optimal dose of selinexor (40 or 60 mg) in combination with R-GDP in patients (n=120) with RR DLBCL. Patients ≥18 years with 1-3 prior lines of therapy and ECOG performance status ≤2 who are not intended for HSCT or CAR-T therapy are randomized 1:1:1 to one of 3 treatment arms: Arm 1: selinexor 40 mg+R-GDP (S40+R-GDP); Arm 2: selinexor 60 mg+R-GDP (S60 + R-GDP); Arm 3: R-GDP. Combination treatment will be given for up to 6 cycles (21 days/cycle). After completing the SR-GDP combination therapy (EoC), patients in Arms 1 and 2 who reach at least partial response (PR), will receive weekly single-agent selinexor 60 mg (28 days/cycle) as "continuous therapy" until disease progression (PD) or unacceptable toxicity. After PD, patients will be followed up for survival. Patients in the R-GDP arm will be followed up for PD and survival. Patients who are ineligible for HSCT due to an active disease, or those who have primary refractory DLBCL, defined as no response or relapse within 6 months after ending first-line treatment, will be allowed to enroll in the study (up to 15% and 25%, respectively of all patients enrolled). The primary endpoint of the study is ORR according to the Lugano 2014 criteria. Secondary endpoints include PFS, OS, ORR-EoC, DOR and incidence and severity of adverse events. Figure 1 Figure 1. Disclosures Pinto: Takeda: Consultancy; MSD: Honoraria; Incyte: Honoraria; Roche: Honoraria, Speakers Bureau; Bristol Myers Squibb-CELGENE: Honoraria. Yimer: Texas Oncology: Current Employment; Pharmacyclics: Speakers Bureau; Amgen: Speakers Bureau; Sanofi: Speakers Bureau; GSK: Speakers Bureau; Beigene: Speakers Bureau; Janssen: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau. Manda: Morphosys: Honoraria; Genmab: Current equity holder in publicly-traded company. Canales: Sanofi: Consultancy; Incyte: Consultancy; Novartis: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; iQone: Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Gilead/Kite: Consultancy, Honoraria; Eusa Pharma: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria. Jurczak: European Medicines Agency, Sandoz-Novartis, Janssen China R&D, BeiGene, Epizyme, Acerta, AstraZeneca: Consultancy; AbbVie, AstraZeneca, Bayer, BeiGene, Celtrion, Celgene, Debbiopharm, Epizyme, Incyte, Janssen, Loxo Oncology, Merck, Mei Pharma, Morphosys, Novo Nordisk, Roche, Sandoz, Takeda, TG Therapeutics, Pharmacyclics, Affirmed, Gilead Sciences, Nordic Nanovecto: Research Funding; Jagiellonian University: Ended employment in the past 24 months; Maria Sklodowska-Curie National Research Institute of Oncology: Current Employment; AstraZeneca, BeiGene, Janssen, Loxo Oncology, Sandoz, Roche: Membership on an entity's Board of Directors or advisory committees. Sureda: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau. Ma: Karyopharm Therapeutics Inc.: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Li: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Ingalls: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Arriola: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Arazy: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction Joint bleeding events (BEs) have cumulative, irreversible and debilitating consequences for persons with hemophilia A or B with inhibitors (PwHABI) due to synovitis and joint iron deposition. To limit the long-term consequences of bleeding into joints, early bleed resolution is a primary treatment goal. Eptacog beta (Sevenfact®, HEMA Biologics and LFB) is a new bypassing agent indicated for the treatment and control of BEs in adults and adolescents with hemophilia A or B with inhibitors. In a prospective, randomized, cross-over, phase 3 clinical trial (PERSEPT 1, NCT#02020369) in the first 24 hours following bleed onset, eptacog beta demonstrated dose-dependent improvements in successful clinical response with 2 initial dose regimens (IDRs) (75 µg/kg IDR: 75 µg/kg q3h; and 225 µg/kg IDR: 225 µg/kg followed by 75 µg/kg q3h after 9 hours if necessary; Figure 1). 91% of all mild or moderate BEs achieved hemostatic efficacy at 12 hours (225 µg/kg IDR), as did 82% at 12 hours in the 75 µg/kg IDR. The majority (85%) of mild/moderate BEs treated in PERSEPT 1 were joint BEs. Aims A subset analysis of mild or moderate joint BE data from the PERSEPT 1 trial was performed to investigate the effect of 2 IDRs on clinical response at 3, 9, 12 and 24 hours on joint BEs in PwHABI. IRB approval and informed consent were obtained. Methods At enrollment, male PwHABI (n=27) were randomized to receive BE treatment on either the 75 µg/kg IDR or the 225 µg/kg IDR (Figure 1) for the first 3 months of treatment; subjects were crossed over to the alternate IDR every 3 months. The 12-hour composite endpoint subset analysis for joint BEs used the same success criteria that were used for the primary efficacy endpoint (for all BEs at 12 hours) in PERSEPT 1. Hemostatic efficacy at all other intermediate timepoints and at 24 hours was assessed using a 4-point evaluation scale (an excellent or good evaluation being considered hemostatic efficacy, and moderate or poor being considered a lack of hemostatic efficacy.) BE treatment continued until bleeding ceased as determined by the subject or physician to discontinue treatment. Results A subset of 396 mild/moderate joint BEs were analyzed. The proportion of successfully treated BEs (composite endpoint) at 12 hours was 91.5% [95% CI: 83.4%, 99.6%] on the 225 µg/kg IDR and 80.6% [95% CI: 69.6%, 91.6%] on the 75 µg/kg IDR. At 9 hours, the proportion of BEs with hemostatic efficacy (using the 4-point evaluation scale) from the first dose in the 225 µg/kg IDR was 86.5%; 3- and 24-hour data are shown in Table 1. Conclusions The joint BE success proportion following a first dose in the 225µg/kg IDR at 3 hours was 85.2%; joint BEs treated by the 75µg/kg IDR demonstrated a 26.4% 3-hour success proportion. These success proportions demonstrate a dose-dependent onset of action; this effect on efficacy was also observed in the 12- and 24-hour data. At 9 hours, sustained hemostatic efficacy from a single 225 µg/kg dose was observed (86.5%). Overall, both initial dose regimens showed successful resolution of joint BEs with early hemostatic success proportions. Further, the onset of action data supports the concept that a larger initial thrombin burst may result in an earlier effective clot that drives earlier bleed resolution. Further observations of this type are needed to understand the role of rFVIIa in hemostatic clot formation. Disclosures Hermans: Bayer: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; LFB: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; EAHAD: Other; WFH: Other. Ducore:Octapharma: Consultancy; Bayer: Consultancy, Honoraria, Speakers Bureau; HEMA Biologics: Consultancy, Honoraria. Escobar:Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Young:BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Wang:Bayer: Honoraria; Takeda: Honoraria; Genentech: Honoraria; Biomarin: Honoraria; CSL Behring: Honoraria; Bioverativ Inc: Honoraria. Quon:Shire/Takeda: Speakers Bureau; Octapharma: Honoraria; Biomarin: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Bayer: Honoraria; Orthopaedic Institute for Children: Current Employment; Bioverativ/Sanofi: Honoraria, Speakers Bureau. Alexander:HEMA Biologics, LLC: Current Employment, Patents & Royalties: No royalties or benefits. Mitchell:HEMA Biologics: Consultancy. Al-Sabbagh:LFB: Current Employment. Bonzo:International Association for Statistical Computing: Other; International Statistics Institute: Other; American Statistical Association: Other; LFB USA, Inc.: Current Employment.

BackgroundSystemic lupus erythematosus (SLE) has heterogeneous organ manifestations that occur in different combinations at an individual patient level. Current SLE clinical trial eligibility criteria and efficacy endpoints, based on legacy disease activity measures, have multiple weaknesses. Understanding the frequency with which different organ manifestations are represented in contemporary SLE cohorts is required, to allow focus on the most frequent and impactful manifestations of disease in both eligibility criteria and endpoints.ObjectivesTo report the prevalence of disease activity in individual organ domains in SLE patients, both overall and in patients meeting the most common disease activity cut-off for clinical trial eligibility (SLEDAI2K ≥6).MethodsWe used data from a multinational SLE cohort, prospectively collected between 2013 and 2020. We analysed data from 4,102 patients with criteria-defined SLE, who contributed 42,345 visits with complete SLEDAI-2K assessments. Disease activity assessed using SLEDAI-2K was categorised according to activity in 9 organ systems: central nervous system (CNS), vasculitis, musculoskeletal, renal, cutaneous, serositis, serological, haematological, and fever. Proportions of organ-specific disease activity in the overall cohort, and stratified by total SLEDAI-2K ≥6 or <6, were calculated.ResultsIn the overall cohort, 3,659 patients (89.2%) had SLEDAI-2K >0 on at least one visit (31,290 visits, 73.9%). Serological disease activity was the most prevalent in the cohort overall, affecting 75.5% of patients at least once, followed by renal (41.6%), cutaneous (36.5%), musculoskeletal (20%) and haematological (19%) activity. Infrequent active manifestations affecting <5% of patients were serositis (3.4%), vasculitis (3.4%), CNS (3.0%) and fever (3%).We further examined the prevalence of domain-specific disease activity in patient visits stratified by a SLEDAI-2K cut-off of 6 (Table 1). In patient visits with a SLEDAI-2K>6 (n = 10,031 visits, 24% of total) the most common manifestations were serological (90%) and renal (73%), followed by cutaneous (26%) and musculoskeletal (14%). Conversely, 7.3% of visits with renal, 6.7% with cutaneous, 5.8% with haematological and 1.3% with musculoskeletal activity did not have a SLEDAI-2K ≥6 (Table 1).Table 1.Frequencies and percentages of patient visits with specific organ system disease activity, stratified by total SLEDAI score cut-off of ≥6 vs <6.All visitsSLEDAI<6SLEDAI≥6n = 42,345n = 32,314n =10,031p-value*Serological25,745 (60.8%)16,740 (51.8%)9,005 (89.8%)<0.001Renal9,684 (22.9%)2,367 (7.3%)7,317 (72.9%)<0.001Cutaneous4,806 (11.3%)2,158 (6.7%)2,648 (26.4%)<0.001Haematological2,615 (6.2%)1,862 (5.8%)753 (7.5%)<0.001Musculoskeletal1,856 (4.4%)422 (1.3%)1,434 (14.3%)<0.001Serositis255 (0.6%)81 (0.3%)174 (1.7%)<0.001Vasculitis250 (0.6%)0250 (2.5%)<0.001CNS200 (0.5%)0200 (2.0%)<0.001Fever149 (0.4%)59 (0.2%)90 (0.9%)<0.001*P-values derived from Pearson’s Chi-Squared tests.ConclusionSerological, renal, cutaneous, musculoskeletal and haematological manifestations predominate in patients with active SLE in our cohort, with other organs only rarely affected. Measures of improvement in SLE trial endpoints could focus on measuring change in these systems, and omit detailed analysis of rare events. Conversely, a notable proportion of patients with active disease in commonly affected organ domains had SLEDAI-2K <6, meaning they would be excluded from clinical trials. Incorporation of organ-specific activity measures and inclusion criteria for SLE clinical trials may overcome this limitation and improve recruitment to and results of trials.AcknowledgementsWe acknowledge the unrestricted project grants received from AstraZeneca, BMS, Eli Lilly, GSK, Janssen, Merck Serono, and UCB to support data collection and project management contributing to this work.Disclosure of InterestsKathryn Connelly: None declared, Rangi Kandane-Rathnayake: None declared, Vera Golder: None declared, Worawit Louthrenoo: None declared, Yi-Hsing Chen: None declared, Jiacai Cho: None declared, Aisha Lateef: None declared, Laniyati Hamijoyo: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Sandra Navarra Consultant of: Biogen, Boehringer Ingelheim, Astra Zeneca, Grant/research support from: Janssen, Novartis, Pfizer, Glaxo Smith Kline, Pfizer, Leonid Zamora: None declared, Zhanguo Li Consultant of: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Grant/research support from: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Sargunan Sockalingam Consultant of: Pfizer, AstraZeneca, ZP Therapeutics, Grant/research support from: Pfizer, AstraZeneca, ZP Therapeutics, Yasuhiro Katsumata Grant/research support from: GlaxoSmithKline K.K. AstraZeneca K.K. Sanofi K.K. Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd, Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma, Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Consultant of: AbbVie, Chugai, Mitsubishi-Tanabe, Grant/research support from: AbbVie, Mitsubishi-Tanabe, Eli Lilly Japan, Shereen Oon: None declared, Sang-Cheol Bae: None declared, Fiona Goldblatt: None declared, Sean O’Neill: None declared, Kristine Ng Consultant of: AbbVie, Annie Law: None declared, BMDB Basnayake: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Cherica Tee: None declared, Michael Tee: None declared, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, C.S. Lau Speakers bureau: AstraZeneca UK Ltd, Consultant of: AstraZeneca Pharmaceuticals LP, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Alberta Hoi Speakers bureau: UCB, Janssen, Sandoz, Eli Lilly, Consultant of: AbbVie, GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB.

Introduction The ECHELON-2 study (NCT01777152) demonstrated significantly longer progression-free survival (PFS) and overall survival with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus CHOP in the frontline treatment of patients (pts) with sALCL or other CD30-expressing PTCL and supported the 2018 FDA approval in this setting. Consistent with current guidelines, pts could have received consolidative stem cell transplant (SCT) after treatment at the discretion of the treating investigator. In all pts treated with A+CHP, only 22% (50 of 226) underwent SCT. Herein, we present outcomes from an exploratory analysis of pts in a complete remission (CR) following A+CHP who received an SCT and those who did not. Methods CR rate was defined at the end of treatment (EOT) by independent review per the Revised Response Criteria for Malignant Lymphoma. ALK+ sALCL pts were excluded because they tend to have more favorable outcomes. Consolidative transplant was not considered a PFS event. A univariate analysis of SCT versus no SCT and multivariate analyses adjusting for region and age were performed. Results Sixty-seven percent (76/113 pts) of pts with ALK- sALCL on the A+CHP arm were in CR at EOT and 36% (27/76) of them received SCT. Pts who underwent SCT were younger, with a median age of 50 years (yr) (range 18-68) compared with 59 yr (range 20-85) in those without SCT. Median PFS for pts with SCT was not reached (95% CI 36.57, not estimable [NE]) versus 55.66 mos (95% CI 23.72, 55.66) for pts without SCT. Fifty-nine percent (38/64) of pts with non-sALCL on the A+CHP arm were in CR at EOT and 29% (11/38) of them received SCT. Pts who underwent SCT were younger than those without (median age 57 yr [35-73] vs 66 yr [49-77]). Median PFS for pts who did and did not receive SCT was not reached (95% CI 20.70, NE) versus 33.22 mos (95% CI 8.08, NE), respectively. Prior to treatment start, the intent to transplant in Asian countries among ALK- sALCL and non-ALCL pts was less frequent in comparison to non-Asian countries (13% and 29% vs 49% and 57%, respectively). The proportion of pts ultimately transplanted was also less frequent (13% and 12% in Asia versus 32% and 23% in non-Asian countries). Standard PFS and multivariate proportional hazards regression analyses favored the use of SCT in PTCL pts in a CR after A+CHP (Table). Conclusions Numerical PFS estimates favor the use of SCT in PTCL pts in a CR after A+CHP; however, sample sizes are small. It is also recognized that unknown confounders may impact this post-hoc analysis. We observed that use of SCT was infrequent in Asian countries, suggesting regional practice differences. The overall impact of consolidative SCT remains unconfirmed, including in patients treated with A+CHP. Further studies are needed to establish its role in this setting. Table Disclosures Savage: BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Horwitz:Millennium/Takeda: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Trillium: Research Funding; Infinity/Verastem: Consultancy, Research Funding; Aileron: Research Funding; Kura: Consultancy; Affimed: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Trillium: Research Funding; Portola: Consultancy; Forty-Seven: Research Funding; Mundipharma: Consultancy; Celgene: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Astex: Consultancy; Astex: Consultancy; Celgene: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Innate Pharma: Consultancy; Affimed: Consultancy; Affimed: Consultancy; Kura: Consultancy; ADCT Therapeutics: Research Funding; Kyowa Hakko Kirin: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Hakko Kirin: Consultancy; Astex: Consultancy; Miragen: Consultancy; Celgene: Consultancy, Research Funding; Mundipharma: Consultancy; Innate Pharma: Consultancy; Kura: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Astex: Consultancy; ADCT Therapeutics: Research Funding; Affimed: Consultancy; Portola: Consultancy; Miragen: Consultancy; Aileron: Research Funding; Trillium: Research Funding; Seattle Genetics: Consultancy, Research Funding; Portola: Consultancy; Innate Pharma: Consultancy; Forty-Seven: Research Funding; Miragen: Consultancy; Kyowa Hakko Kirin: Consultancy; Aileron: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Consultancy, Research Funding; Miragen: Consultancy; ADCT Therapeutics: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Kura: Consultancy; Innate Pharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Forty-Seven: Research Funding; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Aileron: Research Funding; Kyowa Hakko Kirin: Consultancy; Trillium: Research Funding; Forty-Seven: Research Funding; Portola: Consultancy; Mundipharma: Consultancy. Advani:Regeneron: Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Research Funding; Forty-Seven: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cell Medica, Ltd: Consultancy; Janssen: Research Funding; Merck: Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Infinity Pharma: Research Funding; Celgene: Research Funding; Kura: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stanford University: Employment, Equity Ownership; Seattle Genetics: Consultancy, Research Funding; Agensys: Research Funding. Domingo-Domenech:Roche: Other: Travel expenses; Seattle Genetics: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Bristol-Myers Squibb: Other: Travel expenses. Rossi:Daiichi-Sankyo: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Mundipharma: Honoraria; BMS: Honoraria; Sandoz: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Morschhauser:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Research Funding. Alpdogan:Seattle Genetics, Inc.: Research Funding. Tobinai:Meiji Seika: Honoraria; Takeda Pharmaceutical: Consultancy, Honoraria, Research Funding; Mundi Pharma: Consultancy, Honoraria, Research Funding; AbbVie: Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Verastem: Honoraria; Zenyaku Kogyo: Consultancy, Honoraria; Yakult: Honoraria; Bristol-Myers Squibb: Honoraria; HUYA Bioscience: Consultancy, Honoraria; Janssen Pharmaceutical: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Solasia: Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Ono Pharmaceutical: Consultancy, Honoraria, Research Funding. Shustov:Seattle Genetics, Inc.: Research Funding. Trneny:Roche: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Gilead sciences: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria. Yuen:Seattle Genetics, Inc.: Other: Travel expenses, Research Funding. Zinzani:Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Truemper:Janssen Oncology: Consultancy; Nordic Nanovector: Consultancy; Seattle Genetics, Inc.: Research Funding; Mundipharma: Research Funding; Roche: Research Funding; Takeda: Consultancy, Research Funding. Illidge:Div of Cancer Sciences, Faculty of Biology, Medicine and Health, Univ of Manchester, National Institutes of Health and Research Biomedical Research Center, Manchester Academic Health Sciences, Christie Hospital National Health Service Foundation Trust: Employment; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics, Inc.: Research Funding. O'Connor:Spectrum Pharma: Consultancy, Other: Travel expenses, Research Funding; Roche: Research Funding; Seattle Genetics, Inc.: Consultancy, Other: Travel expenses, Research Funding; Allos Therapeutics: Consultancy; Acetylon Pharma: Other: Travel expenses, Research Funding; Celgene: Research Funding; Millenium: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Novartis: Consultancy, Honoraria. Pro:Kyowa Hakka Kirin: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Celgene: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Other: Travel Expenses, Research Funding. Little:Takeda Pharmaceuticals: Employment. Bunn:Takeda Pharmaceuticals: Employment. Fenton:Seattle Genetics, Inc.: Employment, Equity Ownership. Manley:Seattle Genetics: Employment, Equity Ownership. Iyer:Incyte: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics, Inc.: Research Funding; Genentech/Roche: Research Funding; Novartis: Research Funding; Arog: Research Funding.

Background: Umbralisib is an oral, once-daily, dual inhibitor of phosphatidylinositol-3-kinase-delta (PI3Kδ) and casein kinase-1ε (CK1ε) that exhibits improved selectivity for the delta isoform of PI3K. The UNITY-NHL trial (NCT02793583) is a multicenter, open-label, registration directed Phase 2 study designed to evaluate the safety and efficacy of umbralisib in previously treated NHL patients (pts). Previously reported results in pts with relapsed/refractory (R/R) marginal zone lymphoma (MZL) demonstrated that umbralisib was active with a manageable safety profile. In contrast with other PI3K inhibitors, there was a low incidence of immune-mediated toxicities with umbralisib, possibly attributable to enhanced selectivity for the PI3Kδ isoform as well as inhibition of CK1ε. Herein, we present results from the final analysis of the iNHL population treated with single agent umbralisib. Methods: Eligible pts had histologically confirmed iNHL: MZL (splenic, nodal, extranodal), follicular lymphoma (FL; Gr 1, 2, 3a), or small lymphocytic lymphoma (SLL). MZL pts were R/R to ≥1 prior lines of treatment, which must have included an anti-CD20, while FL and SLL pts were R/R to ≥2 prior lines, which had to include an anti-CD20 and an alkylating agent. Umbralisib was administered orally at 800 mg once-daily in 28-day treatment cycles until disease progression or unacceptable tolerability. The primary endpoint of the study was overall response rate (ORR) as assessed by an independent review committee (IRC), according to the revised IWG criteria (Cheson 2007). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), time to response (TTR), and safety. Pneumocystis jiroveci pneumonia (PCP) and anti-viral prophylaxis were mandated for all pts. Results: 208 iNHL pts received at least 1 dose of umbralisib, including 69 MZL, 117 FL, and 22 SLL pts. The median duration of exposure was 8.4 mos (range 0.2 - 27.0), median age was 66, and 56.7% were male. Pts had received a median of 2 prior regimens (range 1 - 10) with 46.1% having received ≥ 3 regimens. FL patients had a median of 3 prior regimens. With a median follow up of 27.8 mos, MZL pts had an ORR of 49.3% (95% CI 37.0% - 61.6%) with 15.9% achieving a complete response (CR), and a Disease Control Rate (DCR: CR+PR+SD) of 82.6%. ORR was consistent amongst MZL subtypes. The median TTR was 2.8 months (95% CI 2.7 - 2.9). The median profession-free survival (PFS) was not reached (95% CI 12.1 mos - not evaluable [NE]) with an estimated 12-month PFS rate of 64.2%. The median DoR was not reached (95% CI 10.3 mos - NE), and no pts who achieved CR have experienced disease progression to date. With a median follow up of 27.5 mos, FL pts had an ORR of 45.3% (95% CI 36.1% - 54.8%) with 5.1% achieving a CR, and a DCR of 79.5%. The median TTR was 4.6 mos (95% CI 3.0 - 5.6). The median PFS was 10.6 mos (95% CI 7.2 - 13.7) with an estimated 12-month PFS rate of 45.9%. The median DoR was 11.1 mos (95% CI 8.3 - 15.6). With a median follow up of 29.3 mos, SLL pts had an ORR of 50.0% (95% CI 28.2 - 71.8) with 4.5% achieving a CR, and a DCR of 86.4%. The median TTR was 2.7 mos (95% CI 2.4 - 2.8). The median PFS was 20.9 mos (95% CI 7.4 - 24.1) with an estimated 12-month PFS rate of 62.6%. The median DoR was 18.3 mos (95% CI 2.4 - NE). Best % change in target lesions form baseline for pts with at least one post-baseline assessment is shown in the figure. At the data cut-off, 60 pts (26 MZL, 27 FL, 7 SLL) remained on treatment. The most common ≥G3 AEs were neutropenia (11.5%), diarrhea (10.1%) and increased ALT/AST (7.2%). Other AEs of interest included pneumonitis (All G 1.4%; ≥G3 1.0%), and colitis (All G 1.4%; ≥G3 0.5%). Serious AEs were reported in 28.1% of pts, with 24.6% ≥G3. One patient with SLL had a fatal myocardial infarction (unrelated to umbralisib); there were no other G5 AEs. A total of 31 pts (14.9%) discontinued due a treatment-related adverse event (AE). Treatment-related AEs leading to dose reductions occurred in 20 (9.6%) pts. Conclusions: In the Phase 2 UNITY-NHL study, umbralisib achieved meaningful clinical activity in a heavily pretreated iNHL population. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and AE-related discontinuations. These results suggest umbralisib has a favorable benefit-risk profile in this patient population and further development is ongoing. Figure Disclosures Zinzani: Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Sandoz-Novartis: Consultancy; Afimed: Research Funding; Acerta: Consultancy, Research Funding; Pharmacyclics: Research Funding; Bayer: Research Funding; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; TG Therapeutics, Inc.: Research Funding; Celgene: Research Funding; Servier: Research Funding; Takeda: Research Funding; Roche: Research Funding; Merck: Research Funding; MEI Pharma: Research Funding; Janssen China R&D: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy; European Medicines Agency,: Consultancy; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Epizyme: Consultancy; Gilead Sciences: Research Funding; MorphoSys: Research Funding; Nordic Nanovector: Research Funding. Ghosh:Kite/Gilead: Consultancy, Speakers Bureau; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Roche/Genentech: Research Funding; Karyopharm: Consultancy; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol-Myers Squibb: Speakers Bureau; Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau. Derenzini:TG Therapeutics, Inc.: Research Funding. Cheah:Celgene, F. Hoffmann-La Roche, MSD, Janssen, Gilead, Ascentage Pharma, Acerta, Loxo Oncology, TG therapeutics: Honoraria; Celgene, F. Hoffmann-La Roche, Abbvie, MSD: Research Funding. Phillips:Karyopharm: Consultancy; Beigene: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy; Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy; Incyte: Consultancy, Other: travel expenses; Cardinal Health: Consultancy; Bayer: Consultancy, Research Funding; Pharmacyclics: Consultancy. Lech-Marańda:Roche, Amgen, Gilead: Speakers Bureau; Roche, Novartis, Takeda, Janssen-Cilag, Amgen, Gilead, AbbVie, Sanofi: Consultancy. Cheson:Abbvie: Consultancy, Research Funding; Kite: Consultancy; TG Therapeutics: Speakers Bureau; Morphosys: Consultancy; Symbio: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Research Funding; Jannsen: Consultancy; Parexel: Consultancy; Trillium: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees. Caimi:Verastem: Other: Advisory Board; Celgene: Speakers Bureau; Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding. Leslie:BeiGene: Honoraria, Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Chavez:Karyopharm: Consultancy; BeiGene: Speakers Bureau; Bayer: Consultancy; Merck: Research Funding; AbbVie: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Celgene: Consultancy; Morphosys: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Verastem: Consultancy; Pfizer: Consultancy. Fonseca:Bristol-Myers Squibb Company: Speakers Bureau. Babu:Merck: Research Funding; Syndax: Research Funding; AbbVie: Research Funding; Janssen Oncology: Research Funding; TG Therapeutics: Research Funding; Amgen: Research Funding; Sanofi: Research Funding; Lutheran Hospital: Other; Argenx: Consultancy, Research Funding; Nektar: Research Funding; Novartis: Research Funding; Bayer: Honoraria; Lilly: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Fort Wayne Medical Oncology & Hematology: Current Employment, Current equity holder in publicly-traded company; AstraZeneca/MedImmune: Research Funding; AstraZeneca: Consultancy, Honoraria; Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; Boehringer Ingelheim: Consultancy. Hodson:Gilead Sciences: Research Funding. Burke:Bristol Myers Squibb: Consultancy; Verastem: Consultancy; Bayer: Consultancy; Astra Zeneca: Consultancy; Gilead: Consultancy; Seattle Genetics: Speakers Bureau; AbbVie: Consultancy; Morphosys: Consultancy; Adaptive: Consultancy; Epizyme: Consultancy; Kura: Consultancy; Celgene: Consultancy; Adaptive Biotechnologies: Consultancy; Roche: Consultancy. Sharman:TG Therapeutics: Consultancy, Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; BeiGene: Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. O'Connor:Kymera Therapeutics: Current equity holder in private company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: Data Safety Monitoring Committee, Research Funding; TG Therapeutics: Current Employment, Current equity holder in publicly-traded company; Servier: Consultancy; Mundipharma: Other: Consulting; Nomocan: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Astex Pharmaceuticals: Honoraria, Research Funding. Miskin:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sportelli:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Weiss:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Fowler:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Background: Etranacogene dezaparvovec is an investigational gene therapy for hemophilia B (HB) comprising an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) gene with a liver specific promoter. In a Phase 2b study, a single dose of etranacogene dezaparvovec provided mean FIX activity of 41.0% sustained at 1yr post-dose in 3 participants (pts). Although most gene therapy clinical studies exclude pts with pre-existing neutralizing antibodies (NAbs) to the capsid serotype, early clinical studies and nonhuman primate data suggest that generally prevalent titers of anti-AAV5 NAbs may not preclude successful transduction with etranacogene dezaparvovec. Aims: A Phase 3, Health Outcomes with Padua gene; Evaluation in Hemophilia B (HOPE-B; NCT03569891) was established to further assess efficacy and safety of etranacogene dezaparvovec in adults with HB with a wide range of pre-existing NAbs to AAV5. Here we report outcomes at 26 weeks (wks). Methods: HOPE-B is a Phase 3, open-label, single-dose, single-arm, multi-national trial in adult males with severe or moderate-severe HB (FIX≤2%). All pts received routine FIX prophylaxis prior to study. Pts were not excluded based on pre-existing NAbs to AAV5. Pts entered a prospective lead-in period of at least 6 months during which bleeding/factor use was monitored, then received a single intravenous dose of etranacogene dezaparvovec (2x1013 gc/kg). Pts will be followed for 5yrs. Primary endpoints comprised FIX activity (one stage) at 26 and 52wks after dosing and 52wk annualized bleeding rate. For pts with no clean post-treatment FIX samples (≥10d post exogenous FIX), factor activity was imputed as baseline value based on historic disease severity. Secondary endpoints include factor replacement use, adverse events (AEs), and reactive use of corticosteroids. Results: 75 pts were screened, of whom 67 entered lead-in. 54 pts were dosed (44 severe, 10 moderately severe HB) and completed 26wks of follow-up. Mean age (±SD) was 41.5 (15.8) yrs. 38/54 pts (70.4%) had bleeds (n=123) during the lead-in despite prophylaxis, and 23/54 (42.6%) had NAbs to AAV5 at baseline (max titer: 3212.3). Following treatment, FIX activity increased rapidly to a mean (SD; min,max) of 37.2% (±19.6; 1.0, 97.1) at wk26, representing a mean (SD; min,max) change from baseline of 36.0% (±19.7; 0, 96.1 p&lt;0.0001, confirmed by per-protocol sensitivity analysis). No correlation of pre-existing NAbs with FIX activity was identified up to a titer of 678.2; n=52, R2 = 0.078); a single pt had a NAb titer of 3212.3 and did not respond. In addition to this pt, one other pt received a partial dose and remained on prophylaxis; all other pts (96.3%) successfully discontinued routine prophylaxis. 39/54 (72.2%) pts reported 0 bleeds in the first 26wks post-treatment; 15 pts reported a total of 21 bleeds. Mean (SD) annualized FIX consumption (IU/yr/pt) was 292,304 (±171,079) during lead-in, decreasing to 12,622 (±36,466) at wk26 (96.0% reduction, N=54). Overall, 37/54 (68.5%) pts had any treatment-related AE post-treatment, the majority of which were mild (81.5%). No deaths occurred and no treatment-related SAEs were reported. 7 pts had infusion-related reactions; the infusion was discontinued in 1 pt. Treatment-related elevations in liver enzymes were reported in 9 pts and received steroids per protocol. All discontinued steroid use prior to wk26 and FIX activity was preserved in the mild range. In addition to these, the most frequent treatment-related AEs were headache (13.0%) and influenza-like illness (13.0%). No inhibitors to FIX were reported. No relationship between safety and NAbs was observed. Conclusions: The first co-primary endpoint of this study was met. This is the first report of a Phase 3 study in HB and the largest gene therapy trial cohort to date. Following a single dose of etranacogene dezaparvovec, FIX activity increased, without the need for prophylactic immunosuppression, into the mild-to-normal range at 26wks in pts with severe/moderately severe HB. Importantly, this included pts with titers of pre-existing anti-AAV5 NAbs. Pts were able to discontinue prophylaxis and bleeding was abolished in the majority. The safety profile was consistent with early phase AAV5 studies and together these data support a favorable safety and efficacy profile for etranacogene dezaparvovec Disclosures Pipe: HEMA Biologics: Consultancy, Other; Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; ApcinteX: Consultancy; Bayer: Consultancy, Other: Contracted Research; BioMarin: Consultancy, Other: Contracted Research; Takeda: Consultancy; uniQure: Consultancy, Other; Siemens: Other; Pfizer: Consultancy; Freeline Therapeutics: Consultancy, Other: Contracted Research; Novo Nordisk: Consultancy, Other: Contracted Research; Roche/Genentech: Consultancy, Other: Contracted Research; Sangamo Therapeutics: Consultancy; Sanofi Genzyme: Consultancy, Other; Spark Therapeutics: Consultancy. Recht:CSL Behring: Consultancy, Other: personal fees; Genentech: Consultancy, Other: personal fees, Research Funding; Pfizer: Consultancy, Other: personal fees, Research Funding; BioMarin: Research Funding; Takeda: Consultancy, Other: personal fees, Research Funding; uniQure: Consultancy, Other: personal fees, Research Funding; Novo Nordisk: Consultancy, Other: personal fees, Research Funding; Spark: Research Funding; Bayer: Research Funding; Grifols: Research Funding; Hema Biologics: Consultancy, Research Funding; LFB: Research Funding; Octapharma: Research Funding; Catalyst Biosciences: Consultancy; Kedrion: Consultancy; Sanofi: Consultancy, Research Funding. Key:Uniqure: Consultancy; Grifols: Research Funding; Takeda: Research Funding; Novo Nordisk: Other: Chair of Grants Committee. Leebeek:Shire/Takeda: Research Funding; uniQure: Consultancy; Shire/Takeda: Consultancy; BioMarin: Consultancy; SOBI: Other: Travel grant; Roche: Other: DSMB member for a study; CSL Behring: Research Funding. Castaman:Bayer, Roche, Sobi, Grifols, Novo Nordick, Werfen, Kedrion: Consultancy, Honoraria, Speakers Bureau; CSL Behring, Pfizer, Sobi: Research Funding; Ablynx, Alexion, Bayer, Takeda, CSL Behring, Novo Nordisk, Pfizer, Roche,Sanofi, SOBI, uniQure: Membership on an entity's Board of Directors or advisory committees. Lattimore:uniQure: Other: Study Steering Committee member. Van Der Valk:Baxalta: Research Funding. Peerlinck:Bayer: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; NovoNordisk: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Roche: Research Funding; Sobi: Consultancy; Takeda: Consultancy, Research Funding. Coppens:Roche: Research Funding; Portola/Alexion: Research Funding; Sanquin Blood Supply: Research Funding; uniQure: Research Funding; NovoNordisk: Consultancy; Pfizer: Consultancy; Sobi: Consultancy; Medcon International: Consultancy; MEDtalks: Consultancy; Bayer: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding; Daiichi Sankyo: Research Funding. O'Connell:uniQure: Consultancy; F. Hoffmann-La Roche Ltd, Novo Nordisk, SOBI: Speakers Bureau; SOBI: Research Funding. Pasi:Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; uniQure: Other: Grants and nonfinancial support , Research Funding; ApcinteX: Consultancy, Other: Personal fees ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Roche: Honoraria, Other; Sobi: Consultancy, Honoraria, Other; Tremeau: Consultancy. Kampmann:Uniqure: Research Funding, Speakers Bureau; Shire Pharmaceuticals: Speakers Bureau. Meijer:Pfizer: Research Funding; Sanquin: Speakers Bureau; Bayer: Speakers Bureau; Sanquin: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Speakers Bureau; BMS: Speakers Bureau; Aspen: Speakers Bureau; Uniqure: Consultancy. von Drygalski:Biomarin: Consultancy; Bioverativ/Sanofi Genzyme: Consultancy; NovoNordisk: Consultancy; Pfizer: Consultancy; uniQure: Consultancy; Hematherix Inc.: Membership on an entity's Board of Directors or advisory committees. Young:Genentech/Roche, Grifols, and Takeda: Research Funding; BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy. Hermans:WFH: Other; EAHAD: Other; LFB: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau. Astermark:Bayer, CSL Behring, Novo Nordisk, Octapharma, Roche, Sobi, Spark, Takeda, uniQure: Consultancy; uniQure: Research Funding. Klamroth:Bayer: Consultancy, Research Funding, Speakers Bureau; Biomarin: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Roche/Chugai: Consultancy, Speakers Bureau; Takeda/Shire: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Biotest: Speakers Bureau; LEO: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lemons:uniQure: Research Funding. Visweshwar:Biogen Idec: Membership on an entity's Board of Directors or advisory committees. Escobar:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Biomarin, Genetech/Roche, CSL Behring, Kedrion, Magellan Healthcare: Honoraria. Gomez:Global Blood Therapeutics: Speakers Bureau. Kruse-Jarres:CSL Behring, Genentech, Inc., Spark: Research Funding; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Honoraria; F. Hoffmann-La Roche Ltd: Speakers Bureau; Biomarin, Chugai Pharmaceutical Co., CSL Behring, CRISPR Therapeutics, Genentech, Inc.: Consultancy. Kotowski:uniQure: Research Funding. Quon:Orthopaedic Institute for Children: Current Employment; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Octapharma: Honoraria; Shire/Takeda: Speakers Bureau. Wang:Bayer: Honoraria; Takeda: Honoraria; Genentech: Honoraria; Biomarin: Honoraria; CSL Behring: Honoraria; Bioverativ Inc: Honoraria; Catalyst Biologics: Consultancy; NovoNordisk: Consultancy; Hema biologics / LFB: Consultancy. Wheeler:Takeda: Membership on an entity's Board of Directors or advisory committees; uniQure: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Sawyer:uniQure: Current Employment, Current equity holder in publicly-traded company. Verweij:uniQure: Current Employment. Colletta:uniQure: Current Employment. Bajma:uniQure: Current Employment. Gut:uniQure: Current Employment. Miesbach:Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Freeline: Consultancy, Membership on an entity's Board of Directors or advisory committees; LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; uniQure: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Etranacogene dezaparvovec is an investigational gene therapy

We assessed long-term safety and efficacy of CT-P10 and rituximab in patients with newly diagnosed low-tumour-burden follicular lymphoma (LTBFL), and following a single transition from rituximab to CT-P10. This double-blind, parallel-group, active-controlled phase 3 trial randomized patients with CD20+ LTBFL to receive CT-P10 or US-sourced rituximab (375 mg/m2 intravenous). Induction therapy (weekly for 4 cycles) was followed by a 2-year maintenance period for patients achieving disease control (CR, CRu, PR and SD). During the maintenance, CT-P10 or rituximab were administered every 8 weeks (6 cycles) in the first year and additional CT-P10 was administered every 8 weeks (6 cycles) in the second year. Secondary endpoints (reported here) were overall response rate during the study period, progression-free survival, time-to-progression, and overall survival. Safety and immunogenicity were also evaluated over the study period. Between Nov 9, 2015 and Jan 4, 2018, 258 patients were randomised (130 CT-P10; 128 rituximab). Over the study period, 115 (88%; CT-P10) and 111 (87%; rituximab) patients achieved overall response. At a median follow-up of 29·2 months (IQR: 26·1-33·7), median progression-free survival, time-to-progression, and overall survival were not estimable. The KM estimates (95% CI) for OS at 36 months were 98% (93-99) and 97% (89-99) in the CT-P10 and rituximab groups, respectively. Corresponding values for PFS were 80% (70-87) and 68% (54-79), while results for TTP were 82% (72-88) and 68% (54-79) in the CT-P10 and rituximab groups, respectively. (Figure A. OS; Figure B. PFS and Figure C. TTP) Over the study period, 114 (88%) and 104 (81%) patients in the CT-P10 and rituximab groups, respectively, experienced at least one treatment-emergent adverse event (TEAE) and 14 (11%) patients in each group experienced TE-serious adverse events (TESAEs). There were no unexpected safety findings observed during the second year of the maintenance period after single transition from rituximab to CT-P10. Figure 1 Disclosures Kwak: Celltrion Healthcare: Membership on an entity's Board of Directors or advisory committees; Xeme Biopharma/Theratest: Other: equity; CJ Healthcare: Consultancy; Sellas Life Sciences Grp: Consultancy; Enzychem Life Sciences: Membership on an entity's Board of Directors or advisory committees; Antigenics: Other: equity; InnoLifes, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pepromene Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Consultancy. Sancho:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Gelgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Menne:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Other: Travel costs, Speakers Bureau; Pfizer: Honoraria, Other: Travel costs, Speakers Bureau; Celgene: Honoraria, Other: Travel grants; Roche: Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Astra Zeneca: Research Funding; Takeda: Honoraria, Speakers Bureau. Jurczak:Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Acerta: Research Funding; Bayer: Research Funding; Janssen: Research Funding; MeiPharma: Research Funding; Pharmacyclics: Research Funding; Roche: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding. Trneny:Gilead: Consultancy, Honoraria, Other: Travel Expenses; Janssen: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Celgene: Consultancy; Incyte: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses. Ogura:Cellgene: Honoraria; Chugai: Honoraria; Denovo Biopharma: Membership on an entity's Board of Directors or advisory committees; MejiSeika Pharma: Membership on an entity's Board of Directors or advisory committees; Mundi Pharma: Membership on an entity's Board of Directors or advisory committees; SymBio: Membership on an entity's Board of Directors or advisory committees; TevaTakeda: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Celltrion, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Eisai: Membership on an entity's Board of Directors or advisory committees. Kim:Pfizer: Research Funding; Donga: Research Funding; Mundipharma: Research Funding; F. Hoffmann-La Roche: Research Funding; Kyowa Kirn: Research Funding; Celltrion: Research Funding; JJ: Research Funding. Lee:Celltrion, Inc.: Current Employment. Kim:Celltrion, Inc.: Current Employment. Ahn:Celltrion, Inc.: Current Employment. Buske:Roche, Janssen, Bayer, MSD: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen, AbbVie, Pfizer, Celltrion: Honoraria, Speakers Bureau. OffLabel Disclosure: Rituximab monotherapy to LTBFL patients

Introduction Eptacog beta [Sevenfact®, coagulation factor VIIa (recombinant)-jncw] (HEMA Biologics and LFB) is a human rFVIIa variant indicated for the treatment and control of bleeding events (BEs) in adults and adolescents with hemophilia A or B with inhibitors. Eptacog beta has not yet been approved for perioperative management; therefore, a phase 3 trial (PERSEPT 3, NCT02548143) was initiated to evaluate the safety and efficacy of eptacog beta for the prevention of excessive bleeding and achievement of hemostasis in persons with hemophilia A or B with inhibitors (PwHABI) undergoing elective surgery or other invasive procedures. Aims To determine the perioperative safety and efficacy of eptacog beta in major and minor elective procedures in PwHABI. Methods PERSEPT 3 was a global, multicenter, single-arm, phase 3 trial that enrolled male PwHABI who required elective minor or major procedures. IRB approval was obtained, and all subjects provided informed consent. Immediately prior to the start of the procedure, subjects undergoing minor invasive procedures were administered an initial dose of 75 µg/kg eptacog beta and those undergoing major invasive procedures were administered an initial dose of 200 µg/kg eptacog beta. Additional eptacog beta (75 µg/kg) was administered during the procedure and post-operatively (Table 1). Hemostatic efficacy was assessed using a 4-point evaluation scale during the procedure, immediately following the procedure, at regular post-operative intervals, and 48 hours following the last dose of eptacog beta (hemostatic evaluations were recorded as excellent, good, moderate and poor). The primary efficacy endpoint was the percentage of good and excellent responses (ie, successes) at 48 (±4) h following the final dose of eptacog beta and was based upon the investigators' integrated assessment; taking into consideration the investigators' intraoperative hemostatic assessment; the number of postoperative bleeding events and interventions, and blood transfusions; and the amount of eptacog beta used. Results Twelve male subjects (age 2-56 years; median 20 years) were enrolled at 8 sites in 5 countries; all subjects had severe hemophilia A with inhibitors. Six minor procedures [circumcision (3) and tooth extraction (3)] and 6 major procedures (left transtibial amputation, hip replacement, orthopedic knee surgery, amputation of the left leg, left knee joint endoprosthesis removal, and left ankle achilloplasty) were evaluated. The primary efficacy endpoint is shown in Table 2: the success proportion was 67% for major procedures and 100% for minor procedures. The intraoperative efficacy of eptacog beta was rated as good or excellent in all 12 procedures (100% success); mean estimated actual intraoperative blood loss was lower than the mean maximum predicted blood loss for a patient without a bleeding disorder undergoing the same procedure. Efficacy 24 hours following procedure completion was rated as good or excellent in all procedures where data were reported (major, 4/4; minor, 6/6). One subject (major procedure) was withdrawn from the study due to an adverse event (postprocedural hematoma); this subject subsequently received aPCC and NSAIDs and experienced blood loss anemia and GI hemorrhage. One subject (minor procedure) withdrew consent. Other nontreatment-related adverse events included postoperative anemia, post-procedural hemorrhage, procedural pain, wound secretion and hemorrhage. No allergic, hypersensitivity, or anaphylactic events were reported; no anti-eptacog beta antibodies were observed; and no thromboembolic events occurred. Conclusions This controlled study demonstrated the efficacy and safety of 2 different dose regimens of eptacog beta in minor and major elective procedures. The intraoperative hemostatic efficacy of eptacog beta was rated as good or excellent in all major and minor procedures, and the success proportion 48h following the final dose (primary efficacy endpoint) was 82% overall. The breadth of procedures examined (ranging from circumcision and tooth extraction to amputation and hip replacement), low mean blood loss, and high intraoperative efficacy suggests that eptacog beta may be successfully utilized in a variety of minor and major procedures. This study provides useful perioperative data for providers who manage congenital hemophilia A or B patients with inhibitors. Disclosures Escobar: National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Quon:Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Shire/Takeda: Speakers Bureau; Octapharma: Honoraria; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Orthopaedic Institute for Children: Current Employment; Bioverativ/Sanofi: Honoraria, Speakers Bureau. Leissinger:Bayer: Consultancy; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; HEMA Biologics: Consultancy; Takeda: Consultancy; Uniqure: Consultancy; Kedrion: Consultancy; Spark: Consultancy. Luck:Orthopaedic Institute for Children: Research Funding; National Hemophilia Foundaton: Honoraria, Speakers Bureau; Board of Trustees, Orthopaedic Institute for Children: Membership on an entity's Board of Directors or advisory committees. Al-Sabbagh:LFB: Current Employment. Bonzo:LFB USA, Inc.: Current Employment; American Statistical Association: Other; International Statistics Institute: Other; International Association for Statistical Computing: Other. Mitchell:HEMA Biologics: Consultancy. Alexander:HEMA Biologics, LLC: Current Employment, Patents & Royalties: No royalties or benefits. Hermans:Bayer: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; LFB: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; EAHAD: Other; WFH: Other. OffLabel Disclosure: SEVENFACT(R) [eptacog beta, coagulation factor VIIa (recombinant)-jncw] is a human rFVIIa variant indicated for the treatment and control of bleeding events (BEs) in adults and adolescents with hemophilia A or B with inhibitors. Eptacog beta is not yet indicated for perioperative management

Background: In the daily practice, clinical effectiveness of pegfilgrastim compared to that of daily filgrastim in patients with malignant lymphoma is still unclear. This study aimed to clarify the effectiveness of pegfilgrastim versus daily filgrastim, using a national inpatient database in Japan. Study Design and Methods: We retrospectively reviewed 18095 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who received the first R-CHOP treatment between July 2007 and March 2017. Patients who received primary G-CSF prophylaxis were divided into pegfilgrastim group and filgrastim group. Outcomes included incidence of febrile neutropenia, all-cause in-hospital death, length of hospital stay, and total costs. To account for measured confounding, patients' characteristics were adjusted using two different propensity score utilizing methods: propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW). Instrumental variable (IV) analysis was also performed to account for unmeasured confounding. Results: We identified 1299 patients in the pegfilgrastim group and 2203 patients in the filgrastim group. FN occurred in 380 of the 3502 (11%) total patients with a median of 9 days (interquartile range [IQR] 7-10) after the initiation of the chemotherapy. All-cause in-hospital death occurred in 94 (2.7%) of 3502 patients. Median of hospital stay was 17 days (IQR 13-22), and total medical costs during hospitalization were 7300 (IQR 5700-9500) in USD. By one-to-one PSM, 1294 patients for both the pegfilgrastim and filgrastim groups were selected. Pegfilgrastim was administered 2 days (median, IQR 1-3) after the chemotherapy. Daily filgrastim administration was initiated 5 days (median, IQR 3-6) after the chemotherapy, and continued for 6 days (median, IQR 2-7). Compared with the filgrastim group, the pegfilgrastim group showed significant lower risk of the FN incidence (risk difference 6.1%, 95% confidence interval [CI] 4.1-8.1) and all-cause in-hospital mortality (risk difference 0.9%, 95% CI 0.05-1.8). In similar, stabilized IPTW showed that pegfilgrastim group was significantly associated with the lower risk of FN (risk difference 7.0%, 95% CI 5.1-8.9) and in-hospital mortality (risk difference 1.8%, 95% CI 0.9-2.7). In PSM, the length of hospital stay and total costs during hospitalization were also significantly decreased in the pegfilgrastim group compared to the filgrastim group (percent reduction 34% [95% CI 31-37], percent reduction 12% [95% CI 9-15], respectively). Stabilized IPTW also showed the significant percent reduction of the pegfilgrastim group to the filgrastim group for length of hospital stay and total costs (31% [95% CI 25-35], 19% [95% CI 13-24], respectively). In the sensitivity analyses, IV methods showed significantly lower FN susceptibility (odds ratio 0.14, 95% CI 0.07-0.26). However, pegfilgrastim was not associated with the reduction in susceptibility of in-hospital mortality (odds ratio 0.93, 95% CI 0.23-3.70). The ratio of the pegfilgrastim group to the filgrastim group for length of hospital stay and total costs were 55% (95% CI 51-60) and 78% (95% CI 73-84), respectively. Conclusion: Pegfilgrastim contributed to lower susceptibility of FN. Total length of hospital stay and medical costs were also decreased in the pegfilgrastim group. Disclosures Jo: Tsumura: Other: Laboratory of joint program, Research Funding. Miyauchi:kyowa Kirin: Research Funding. Toyama:Bristol-Myers Squibb: Speakers Bureau; Nippon Shinyaku Co., Ltd.: Speakers Bureau; Eisai Co., Ltd.: Speakers Bureau; Celgene K.K.: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Speakers Bureau; Chugai Pharmaceutical Company: Speakers Bureau; Takeda Pharmaceutical Company Limited.: Speakers Bureau; Kyowa Hakko Kirin Co., Ltd.: Speakers Bureau; Daiichi Sankyo Conpany: Speakers Bureau; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau. Kurokawa:Bristol-Myers Squibb: Speakers Bureau; Otsuka Pharmaceutical Co., Ltd.: Research Funding, Speakers Bureau; Janssen Pharmaceutical K.K.: Speakers Bureau; Novartis Pharma K.K.: Research Funding; Yakult Honsha Company: Speakers Bureau; Daiichi Sankyo Conpany: Speakers Bureau; Eisai Co., Ltd.: Research Funding, Speakers Bureau; Celgene K.K.: Consultancy, Speakers Bureau; Nippon Shinyaku Co., Ltd.: Research Funding; Kyowa Hakko Kirin Co., Ltd.: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire Japan K.K.: Speakers Bureau; Pfizer Japan Inc.: Research Funding; Sumitomo Dainippon Pharma Co.,Ltd.: Research Funding, Speakers Bureau; Shionogi & Co., Ltd: Consultancy, Honoraria; MSD K.K.: Consultancy, Research Funding, Speakers Bureau; Chugai Pharmaceutical Company: Consultancy, Research Funding, Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Takeda Pharmaceutical Company Limited.: Research Funding, Speakers Bureau; Teijin Limited: Research Funding; ONO PHARMACEUTICAL CO., LTD.: Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Bioverativ Japan ltd.: Consultancy.

Abstract Background: Cirmtuzumab (Cirm) is a humanized monoclonal antibody that inhibits the tumor promoting activity of ROR1 and has demonstrated additive/synergistic activity with many anticancer agents, including ibrutinib (Ibr). Methods: Patients (Pts) with relapsed or refractory (RR) MCL or treatment-naïve (TN) or RR CLL were enrolled. In Part 1 (Dose Escalation), doses of Cirm IV q2wks x5 then q4wks of 2-16 mg/kg and 300 or 600 mg were examined. Safety of Cirm alone was assessed during the first 28 days, then Ibr was started at approved doses for each indication. Cirm 600 mg IV q2wks x3 then q4wks in combination with Ibr starting day 0 was chosen as the recommended dosing regimen for use in Part 2 (Expansion) and Part 3 (CLL only, Cirm/Ibr vs. Ibr). MCL Part 1 is closed, and Part 2 is open for enrollment. CLL Parts 1, 2 & 3 are closed for enrollment. Results: As of 18Jun2021 data cutoff, 28, 34 and 28 pts were treated in MCL Parts 1 & 2, CLL Parts 1 & 2, and CLL Part 3 (Cirm/Ibr (n=18) or Ibr (n=10)). In Parts 1 & 2 MCL, the median number (#) of prior systemic regimens was 1.5 (1-4) including pts relapsing after Ibr (n=4), auto-SCT (n=6), auto-SCT/allo-SCT (n=1), or auto-SCT/CAR-T (n=1). Ki-67 ≥30% and extra-nodal disease was present in 54% and 68% of pts, respectively. The median # of prior systemic regimens for CLL Parts 1 & 2 and CLL Part 3 (RR), was 2 (1-15) including auto-SCT (n=1), and 2 (1-6). Pts entered with Rai staging ≥ Grade 2 in 71% and 64%. Safety (MCL and CLL): Most frequent treatment emergent (TEAEs) (≥30%) for both MCL and CLL pts treated with Cirm/Ibr (N=80), (all grades; regardless of causality) included contusion & fatigue (both 40.0%), and diarrhea (37.5%). Most frequent (≥5%) Grade ≥3 TEAEs, regardless of causality included hypertension (10.0%), fatigue, neutropenia, pneumonia, and atrial fibrillation (all 6.3%), leukocytosis and anemia (both 5.0%). Grade ≥3 TEAEs of myelosuppression, regardless of causality, include anemia (5.0%), thrombocytopenia (1.3%), and neutropenia (6.3%). Most TEAEs in MCL or CLL pts were considered related by Investigator to Ibr alone 64% or 84% vs. Cirm alone 14.3% or 16%. Efficacy (MCL): The best response of 20 evaluable pts in Parts 1 & 2 included CR 35%, PR 45%, SD 10%, and 10% PD. At a median follow-up of 14.9 mos., the objective response rate (ORR), clinical benefit rate (CBR) and median duration of response (DOR) for overall, ≥30% Ki-67, and &gt;1 prior systemic regimen subgroups, were 80%, 90% and (not reached) NR (95% CI: 11.9, NR), 81.8%, 81.8% and 13.8 (95% CI: 8.7, NR), and 90%, 100% and NR (95% CI: 8.7, NR). Responses occurred in all evaluable pts who received prior SCT+/- CAR-T (4CR, 2PR) or prior Ibr (2CR, 2PR). The median PFS (mPFS) for overall, pts achieving CR, and &gt;1 prior systemic regimen subgroups were all NR with varying 95% CI: (16.5, NR), (0.03, NR), and (0.03, NR). Efficacy (CLL): The best response of 34 evaluable pts in Parts 1 & 2 included 94.1% ORR, 11.8% CR, 82.3% PR/PR-L, and 5.9% SD for a CBR of 100%. In Part 3, evaluable Cirm/Ibr TN (n=8) or RR (n=7) and Ibr TN (n=4) or RR (n=3) arms achieved 100% or 85.7% and 100% or 100% ORR, 12.5% or 0% and 0% or 0% CR, 87.5% or 85.7% and 100% or 100% PR/PR-L, 0% or 14.3% and 0% or 0% SD. No pts had PD as best response. All pts had a CBR of 100%. For Parts 1 & 2, at a median follow-up of 24.8 mos., the DOR for overall and &gt;1 prior systemic regimen subgroups, was NR (8.3, 35.9) and NR (12.0, 29.6). In Part 3, at a median follow-up of 14.7 mos., the DOR for TN or RR Cirm/Ibr and Ibr arms is NR (7.7, 18.6) or NR (9.2, 14.8) and NR (11.2, 18.5) or NR (8.3, 14.2). The mPFS (Parts 1 & 2) for overall, pts achieving CR, and &gt;1 prior systemic regimen subgroups were NR (9.1, 35.8), NR (95% CI: 22.5, NR), and NR (9.1, 35.2). In Part 3, mPFS for TN or RR Cirm/Ibr and Ibr arms is all NR. Conclusions: Cirm/Ibr is well-tolerated. ORR, CR, DOR, and mPFS were similar across all subgroups of MCL and CLL pts regardless of number of prior systemic regimens or poor risk factors. Striking responses were observed in patients with MCL as evidenced by a mPFS that was NR (95% CI: 16.5, NR), CR of 35%, and a DOR of NR (95% CI: 11.9, NR) within the study period. These data compare very favorably to the mPFS of 12.8 mos, CR of 20%, and a DOR of 18.6 mos., reported for Ibr alone (Rule 2017). For CLL pts treated with Cirm/Ibr, results continue to be encouraging as they mature. The study is ongoing, with MCL enrollment expanded to include Cirm + Ibr in pts who have had an inadequate response to an Ibr regimen, or who are refractory to approved BTKi agents. Figure 1 Figure 1. Disclosures Lee: Oncternal: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Seagen: Research Funding; BMS: Honoraria, Research Funding; Aptitude Health: Honoraria; Guidepoint: Honoraria; Century Therapeutics: Consultancy; Pharmacyclics: Research Funding; Janssen: Honoraria. Choi: Abbvie: Other: Institution: Research Grant/Funding; Pharmacyclics: Other: Institution: Research Grant/Funding; Oncternal: Other: Institution: Research Grant/Funding; Velosbio: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding; Geron: Other: Institution: Research Grant/Funding. Siddiqi: Celgene: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Speakers Bureau; Oncternal: Research Funding; TG Therapeutics: Research Funding. Wierda: Acerta Pharma Inc.: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; AstraZeneca: Research Funding; Cyclacel: Research Funding; Karyopharm: Research Funding; Xencor: Research Funding; Oncternal Therapeutics, Inc.: Research Funding; KITE Pharma: Research Funding; Miragen: Research Funding; Janssen: Research Funding; Gilead Sciences: Research Funding; Juno Therapeutics: Research Funding; Genentech: Research Funding; GSK/Novartis: Research Funding; Sunesis: Research Funding; Loxo Oncology, Inc.: Research Funding; Genzyme Corporation: Consultancy; AbbVie: Research Funding. Tuscano: BMS: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Acrotech: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Abbvie: Research Funding. Leslie: Abbvie: Consultancy, Honoraria; PCYC/Janssen: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Speakers Bureau; Karyopharm Therapeutics: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; BeiGene: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy; Celgene/BMS: Consultancy, Honoraria, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Speakers Bureau; Epizyme: Consultancy, Honoraria, Speakers Bureau; Seagen: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy. Breitmeyer: Oncternal Therapeutics: Current Employment, Membership on an entity's Board of Directors or advisory committees. Yazji: Oncternal Therapeutics: Current Employment. Wang: Oncternal Therapeutics: Current Employment. Wang: OMI: Honoraria; Moffit Cancer Center: Honoraria; Chinese Medical Association: Honoraria; Newbridge Pharmaceuticals: Honoraria; DTRM Biopharma (Cayman) Limited: Consultancy; InnoCare: Consultancy, Research Funding; Scripps: Honoraria; Mumbai Hematology Group: Honoraria; VelosBio: Consultancy, Research Funding; BioInvent: Research Funding; Hebei Cancer Prevention Federation: Honoraria; Epizyme: Consultancy, Honoraria; Anticancer Association: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Lilly: Research Funding; Physicians Education Resources (PER): Honoraria; Dava Oncology: Honoraria; Clinical Care Options: Honoraria; Molecular Templates: Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Juno: Consultancy, Research Funding; Celgene: Research Funding; Genentech: Consultancy; Loxo Oncology: Consultancy, Research Funding; Kite Pharma: Consultancy, Honoraria, Research Funding; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; The First Afflicted Hospital of Zhejiang University: Honoraria; Bayer Healthcare: Consultancy; BGICS: Honoraria; CAHON: Honoraria; Oncternal: Consultancy, Research Funding; CStone: Consultancy. Jamieson: Forty Seven Inc.: Patents & Royalties. Kipps: Genentech-Roche: Consultancy; Gilead Sciences: Consultancy, Honoraria, Other, Speakers Bureau; Janssen: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Roche: Honoraria, Other; MD Anderson Cancer Center: Research Funding; Velos: Research Funding; CRIM: Research Funding; Indy Hematology Review: Other; TG Therapeutics: Other; Verstem: Other, Speakers Bureau; University of California, San Diego: Current Employment; Pharmacyclics/AbbVie: Honoraria, Research Funding; Breast Cancer Research Foundation: Research Funding; SCOR - The Leukemia and Lymphoma Society: Research Funding; National Cancer Institute/NIH: Honoraria, Research Funding; Genentech/Roche: Honoraria; European Research Initiative on CLL (ERIC): Honoraria; Genetech: Honoraria, Other; Celgene: Consultancy, Honoraria, Other, Research Funding; Bionest Partner: Other; DAVA Pharmaceuticals: Speakers Bureau; DAVAOncology: Consultancy, Honoraria, Other; AbbVie: Consultancy, Honoraria, Other, Speakers Bureau; Oncternal Therapeutics, Inc.: Current holder of stock options in a privately-held company, Other: Stock or other ownership, Patents & Royalties: Cirmtuzumab was developed by Thomas J. Kipps in the Thomas J. Kipps laboratory and licensed by the University of California to Oncternal Therapeutics, Inc., which provided stock options and research funding to the Thomas J. Kipps laboratory., Research Funding; Moores Cancer Center: Current Employment; MedImmune Inc: Research Funding; GlaxoSmithKline: Research Funding; Gilead Sciences, Inc.: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an Abbvie Company: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Research Funding; Abbott Laboratories: Consultancy, Research Funding.

Abstract Background: Myelodysplastic Syndromes (MDS) are genetically and hematologically diverse stem cell malignancies pathogenetically linked to constitutive innate immune activation. Other than rare germline mutations and age, the only known predispositions to adult MDS include prior cytotoxic therapy, clonal hematopoiesis, and autoimmune or chronic inflammatory disorders. Few studies investigating the genetic susceptibility to MDS have been performed owing to the limitations of SNP-array sample size. Here, we report the results from the first unbiased genome wide analysis of germline polymorphisms associated with non-del(5q) MDS using a multinational curated data set. Methods: Association analyses were performed on 2 sample sets (set 1: 555 cases, 2,964 controls; set 2: 352 cases, 2,640 controls) and combined by meta-analysis. Standard SNP- and sample-level QC was applied. Haplotype reference consortium (HRC) imputation was done by the Michigan imputation server (Rsq>0.4) providing 23,278,269 markers for analysis. Gene expression sequencing was performed on an independent sample set from the National Taiwan University Hospital (213 MDS cases, 20 healthy donors; HumanHT-12 v4 Expression BeadChip; Chuang et al. Leukemia 2015). Functional analyses were performed as described. Results: Eight MDS associated loci were identified with lead variants, rs6683416, rs34539210, rs341274, rs1634783, rs7099032, rs2947170, rs4404050, and rs1206818, at 1q31.1 (PLA2G4A), 3p14.1 (FAM19A4), 5q21.3 (EFNA5), 6p21.33, 10q23.1 (GRID1), 12q24.32, 15q26.1, and 20q13.12 (EYA2), respctively. Odds ratio (OR) and p-values of each are listed in Table 1. Using gene expression profiling in an independent MDS sample set, we found expression of these five candidate genes was significantly increased in MDS vs controls (p<0.01). Using the same independent sample set, we found higher PLA2G4A and lower EYA2 expression were associated with reduced overall survival (p=0.039 and p=0.037, respectively). Importantly, EYA2 was an independently favorable risk factor irrespective of age, gender and IPSS-R (RR, 0.665; p=0.048). High PLA2G4A expression was associated with NRAS (p<0.001), RUNX1 (p=0.012), ASXL1 (p=0.007), and EZH2 (p=0.038) somatic mutations whereas higher FAM19A4 expression associated with KRAS mutations (p=0.045). Importantly, PLA2G4A, FAM19A4, GRID1, and EYA2 are involved in the regulation of innate immune signaling. We previously reported that across all somatic gene mutation classes, MDS cases biologically converge upon the redox-sensitive, Nlrp3 inflammasome to drive pyroptosis, a caspase-1 mediated innate immune cell death (Basiorka et al. Blood 2016). PLA2G4A encodes phospholipase A2 (PLA2) that inhibits inflammasome activation. Further, PLA2 is required for MAPK phosphorylation of S100A9, a key danger associated molecular pattern (DAMP) and TLR4 ligand implicated in the induction of pyroptosis in MDS progenitors. FAM19A4 encodes a cytokine whose expression is upregulated in response to endotoxin exposure suggesting a role in immune modulation. EYA members activate innate immune response in part through recognition of cytosolic double-stranded DNA, which can serve as a DAMP triggering inflammasome assembly. To investigate the possible role of EYA2 in inflammasome activation in MDS, we overexpressed EYA2 in the monocytic cell line, THP1. EYA2 overexpression induced caspase-1 and maturation of IL-1β, indicating inflammasome activation. These findings were accompanied by NFκB phosphorylation consistent with innate immune signal priming. We next treated MDS primary bone marrow specimens (n=3) with the EYA2 inhibitor, MLS000544460, demonstrating a significant, dose-dependent improvement in colony recovery consistent with restoration of effective hematopoiesis. Conclusion: We describe here the first MDS susceptibility loci ever identified the majority of which have a direct relationship to innate immune activation, a driver of MDS pathogenesis. Expression of genes housing these loci is increased in MDS with demonstrable prognostic and biological relevance. Further, functional studies implicate EYA2 as a novel, biologically rational target for MDS treatment. The direct functions of each polymorphism as well as the potential relationship between these predisposition loci to age-related clonal hematopoiesis merits further investigation. Disclosures Cluzeau: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Speakers Bureau. Sallman:Celgene: Research Funding, Speakers Bureau. Sokol:Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Mallinckrodt Pharmaceuticals: Consultancy. Maciejewski:Ra Pharmaceuticals, Inc: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Apellis Pharmaceuticals: Consultancy; Ra Pharmaceuticals, Inc: Consultancy; Apellis Pharmaceuticals: Consultancy; Alexion Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. List:Celgene: Research Funding.

Background: The outcome of elderly patients with Acute Myeloid Leukemia (AML) is poor and treatment options in these high-risk groups are limited. Recently, venetoclax combinations with hypomethylating agents or low dose cytarabine were approved to treat patients with AML ineligible for intensive chemotherapy. However limited prospective data is available on the safety and efficacy of venetoclax treatment in routine clinical practice. Israel is among the first countries to have approved venetoclax-based combinations as first line therapy for AML and this treatment is fully reimbursed via the national health system. Here we present the initial results of a prospective, multicenter, nationwide trial that sought to assess the use of venetoclax-based therapy in a real-world setting. Methods: A prospective observational nationwide multicenter trial. Newly diagnosed patients with AML were enrolled at the time of venetoclax-based therapy initiation. Demographic, clinical and patient-related baseline characteristics were documented. Treatment patterns, safety and efficacy outcomes are reported. Patient related outcomes were assessed at baseline and after cycle 3 using the EQ-5D-5L and EORTC QLQ-C30 questionnaires. Results: A total of 70 patients were enrolled between August 2019 and June 2020 (data cut off) with a median age of 75 years (range 45-88) and a median follow-up of 74 days (8-232). Two-thirds of patients were males (62.9%). Over one-quarter (28.6%) of patients had an ECOG performance status of 2 or higher; the median modified Charlson Comorbidity Index (CCI) was 0 (range 1-4) with 27.1% with a CCI ≥2. De-novo AML was documented in 44.3%, secondary AML was diagnosed in 52.8% (secondary to MDS (27.1%), MPNs (11.4%) and therapy related AML (14.3%)). European LeukemiaNet (ELN) risk category was favorable, intermediate and adverse in 8.6%, 30% and 42.9%, respectively (Table 1). Time from diagnosis to initiation of therapy was 8 days (median, range 1-38). The main reasons for choosing venetoclax-based low intensity therapy as reported by treating physicians were patient related factors (mainly age&gt;75 years, performance status) in the majority of cases and adverse disease biology predicting poor response to intensive chemotherapy in 17.1%. Of the 57 patients with available data, 38 (67%) initiated therapy in an inpatient setting with a median hospitalization duration of 12 days (range 1-62 days) and 19 (33%) patients started therapy as outpatients. By data cutoff, of 63 patients that initiated therapy 45, 23 and 7 patients completed cycle 1, cycle 3 and cycle 6 assessments, respectively. Complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 23/44 (52.3%) patients that were assessed for best response. Of responding patients, 6 (23%, 5 CRi and 1 Partial Remission (PR)) went on to receive an allogeneic transplantation (median age 70.5 years). Ninety percent of patients received venetoclax in combination with hypomethylating agents (azacytidine n=56, decitabine n=1). The full dose of 400mg was administered in 87% of cases with a median ramp-up duration of 3 days. Dose interruptions, dose modifications and dose discontinuations during follow-up were frequent and occurred in 41%, 35% and 27%, respectively. During therapy 63.5% of patients experienced adverse events (AE) of any grade; severe AE's were recorded in 41.3% of patients. Febrile neutropenia was documented in 22.2% and Tumor Lysis Syndrome (TLS) was documented in 2 patients (grade 2; 3.2%). Early death rates at 30 and 60 days were 6.3% and 11.1%, respectively. Conclusion: In the real-world setting venetoclax-based therapies are effective and associated with manageable toxicity including in the outpatient setting. In routine practice patient-related factors and disease-related factors (disease-risk) both seem to play a role in choice of therapy. Venetoclax treatment in real-life practice in Israel appears to follow general recommendations, is tolerable with approximately 90% of patients achieving target dose. These observational data are expected to provide information on patient selection patterns, efficacy and safety and patient related outcomes in patients not in clinical trial. Table Disclosures Wolach: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; Amgen: Other: Fees for lectures and Consultancy; Janssen: Other: Fees for lectures and Consultancy. Levi:Abbvie Inc: Consultancy, Research Funding. Canaani:Abbvie: Consultancy, Honoraria, Research Funding. Tadmor:AbbVie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Medison: Consultancy, Speakers Bureau; Neopharm: Consultancy, Speakers Bureau; 6. Novartis Israel Ltd., a company wholly owned by Novartis Pharma AG: Consultancy, Speakers Bureau. Tavor:Abbvie: Consultancy, Honoraria, Research Funding. Hellmann:Abbvie: Research Funding. Stemer:Abbvie: Research Funding. Cohen:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Afik:Abbvie Inc: Current equity holder in publicly-traded company. Ofek:Abbvie Inc: Current Employment. Banayan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Kan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Grunspan:Abbvie Inc: Current Employment, Current equity holder in publicly-traded company. Ofran:AbbVie: Membership on an entity's Board of Directors or advisory committees. Moshe:Astellas: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding.

Background:Digital health applications (DHAs) are gaining influence and promise great potential for the monitoring and management of rheumatic and musculoskeletal diseases (RMDs).Objectives:To analyse the impact of the COVID-19 pandemic on RMD patients’ and rheumatologists’ usage, preferences, and perception of digital health applications (DHAs) in Germany.Methods:A web-based national survey was developed by the Working Group Young Rheumatology of the German Society for Rheumatology and the German League against Rheumatism. The prospective survey was distributed via social media, QR-code, and email. Descriptive statistics were calculated, and regression analyses were performed to show correlations.Results:We analysed the responses of 299 patients and 129 rheumatologists. Most patients (74%) and rheumatologists (76%) believed that DHAs are useful in the management of RMDs and felt confident in their own usage thereof (90%; 86%). 38% of patients and 71% of rheumatologists reported that their attitude had changed positively towards DHAs and that their usage had increased due to COVID-19 (29%; 48%).Usage and recommendation of DHAs for both groups are shown in Figure 1:Figure 1.Usage or recommendation of digital health applications. Patients and rheumatologists were asked to indicate the specific digital health applications (DHAs) they used or were recommended.The majority in both groups agreed on implementing virtual visits for follow-up appointments in stable disease conditions. The most reported advantages of DHAs were usage independent of time and place (76.6%; 77.5%). The main barriers were a lack of information on suitable, available DHAs (58.5%; 41.9%), poor usability (42.1% of patients) and a lack of evidence supporting the effectiveness of DHAs (23.2% of rheumatologists) (Table 1).Table 1.Advantages and Barriers of DHA, n (%).AdvantagesBarriersPatientsRheumatologistsPatientsRheumatologistsLocation-Independence229 (76.6)100 (77.5)Too little information175 (58.5)54 (41.9)Time-independence223 (74.6)94 (72.9)Too little evidence of benefits36 (12.0)30 (23.3)Detailed documentation97 (32.4)47 (36.4)Poor quality of current apps47 (15.7)29 (22.5)Cost saving95 (31.8)37 (28.7)Concernsabout data protection52 (17.4)25 (19.4)More information88 (29.4)38 (29.5)Lack of usability126 (42.1)17 (13.2)Independenceof doctors+36 (12.0)-Lack of accessibility4 (1.3)-More flexibility107 (36.8)77 (59.7)High costs4 (1.3)23 (17.8)Preparationfor discussion+46 (15.4)-No suitable equipment17 (5.7)11 (8.5)No advantages at all18 (6.0)1 (0.8)Lack of user competenceNo Need9 (3.0)39 (13.0)-12 (9.3)Patients and rheumatologists were asked about the advantages and barriers of DHAs. Multiple answers were allowed. Patients had two additional potential advantages and potential barriers to choose from*.Only a minority (<10% in both groups) believed that digitalisation has a negative impact on the patient-doctor relationship.Conclusion:The COVID-19 pandemic instigated an increase in patients’ and rheumatologists’ acceptance and usage of DHAs, possibly introducing a permanent paradigm shift in the management of RMDs.Acknowledgements:The authors thank the following persons and societies for their great effort, distributing the online survey: P.Aries, A.Hueber, E.Feist, C.Fiehn, P.Korsten, I.Kötter, F.Mühlensiepen, A.Pfeil, M.Rudwaleit, M.Welcker, S.Zinke, Deutsche Vereinigung Morbus Bechterew e.V., Deutsche Rheuma-Liga Bundesverband e. V., Sklerodermie Selbsthilfe e.V.Disclosure of Interests:Anna Kernder: None declared, Harriet Morf: None declared, Philipp Klemm: None declared, Diana Vossen Speakers bureau: Novartis, Abbvie, Amgen, Consultant of: Abbvie Deutschland GmbH & Co. KG, Bristol-Myer Squibb, Celgene GmbH, Gilead Sciences Inc., Lilly Deutschland GmbH, Medac GmbH, Novartis Pharma GmbH, Pfizer Deutschland GmbH, UCB Pharma GmbH, Grant/research support from: Pfizer, Abbvie, Marco Meyer Consultant of: Medac, Isabell Haase Speakers bureau: Medac, Consultant of: Medac, Grant/research support from: UCB, Abbvie, BMS, Johanna Mucke Speakers bureau: AbbVie Deutschland GmbH & Co. KG, Amgen, Bristol-Myers Squibb, Chugai Pharma Germany GmbH, Celgene GmbH, Gilead Sciences Inc., GlaxoSmithKline, Janssen-Cilag GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Deutschland GmbH and UCB Pharma GmbH., Consultant of: AbbVie Deutschland GmbH & Co. KG, Amgen, Bristol-Myers Squibb, Chugai Pharma Germany GmbH, Celgene GmbH, Gilead Sciences Inc., GlaxoSmithKline, Janssen-Cilag GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Deutschland GmbH and UCB Pharma GmbH., Arnd Kleyer Shareholder of: yes, Speakers bureau: Lilly, Novartis, Consultant of: Abbvie, Lilly, Novartis BMS, Gilead,Janssen, Grant/research support from: Lilly, Novartis, Gilead,, Philipp Sewerin Consultant of: AbbVie, Amgen, Axiom Health, Biogen, Bristol-Myers Squibb, Celgene, Chugai Pharma Marketing Ltd./Chugai Europe, Deutscher Psoriasis-Bund, Fresenius Kabi, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Johnson & Johnson, Lilly, Medi-login, Mediri GmbH, Novartis Pharma, Onkowissen GmbH, Pfizer, Roche Pharma, Rheumazentrum Rhein-Ruhr, Sanofi-Genzyme, Swedish Orphan Biovitrum, and UCB, Grant/research support from: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Bundesministerium fuer Bildung und Forschung (BMBF), Deutsche Forschungsgesellschaft (DFG), Deutscher Psoriasis-Bund, Fresenius Kabi, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Lilly, Novartis Pharma, Pfizer, Rheumazentrum Rhein-Ruhr, Roche Pharma, Sanofi-Genzyme, and UCB, Gerlinde Bendzuck: None declared, Sabine Eis: None declared, Johannes Knitza Consultant of: Abbvie, Novartis, Lilly, Medac, BMS, Sanofi, Amgen, Gilead, UCB, ABATON, GSK, Grant/research support from: Novartis, UCB, Thermofisher, Sanofi, Martin Krusche Speakers bureau: Lilly, Medac, Novartis, Roche/Chugai, Consultant of: Abbvie, Lilly, Gilead, Medac, Novartis, Sobi, BMS, Amgen, GSK, Grant/research support from: Sanofi

Abstract Background : Ibr, an established standard of care in CLL, is a once-daily Bruton tyrosine kinase inhibitor with significant progression-free survival (PFS) and overall survival benefit shown in multiple randomized phase 3 studies in first-line CLL. Ven, an oral BCL-2 inhibitor approved as a single agent or combined with rituximab or obinutuzumab for CLL treatment, achieves high rates of undetectable MRD (uMRD). Ibr and Ven, with distinct and complementary mechanisms of action, work synergistically to mobilize CLL cells from lymph nodes and lymphoid niches, enhance cell killing, and eliminate distinct CLL cell populations. CAPTIVATE (PCYC-1142; NCT02910583) is an international, multicenter phase 2 study evaluating first-line Ibr + Ven in 2 cohorts: MRD and Fixed-Duration (FD). Patients (pts) first received 3 cycles of Ibr followed by 12 cycles of combined Ibr + Ven. In the primary analysis of the MRD cohort, pts with Confirmed uMRD who after fixed duration treatment were randomized to placebo or continued Ibr had similar post-randomization 1-year DFS rates (95% and 100%, respectively) (Wierda, ASH 2020). Two-year post-randomization results are presented. Methods : Pts aged &lt;70 years with previously untreated CLL received 3 cycles of Ibr lead-in then 12 cycles of combined Ibr + Ven (oral Ibr 420 mg/day; oral Ven ramp-up to 400 mg/day). During cycle 16, pts with Confirmed uMRD (defined as uMRD serially over ≥2 assessments ≥3 mo apart, and in both peripheral blood [PB] and bone marrow [BM]) were randomized 1:1 to receive double-blind treatment with placebo or single-agent Ibr. Pts who did not meet the definition of Confirmed uMRD were randomized 1:1 to receive open-label treatment with single-agent Ibr or continued Ibr + Ven. Endpoints presented include 2-year DFS rate (defined as survival without progression [PD] or MRD relapse post-randomization) in pts with Confirmed uMRD randomized to placebo vs Ibr, rates of uMRD (&lt;10 -4 by 8-color flow cytometry), investigator-assessed best response per iwCLL, investigator-assessed PFS, and adverse events (AEs). Results : 164 pts were enrolled. Median age was 58 years (range, 28-69). High-risk features included unmutated IGHV (60% of pts), del(17p)/TP53 mutation (20%), complex karyotype (19%), and del(11q) without del(17p) (17%). After 12 cycles of Ibr + Ven, 149 pts were randomized: Confirmed uMRD to placebo (n=43) or Ibr (n=43); without Confirmed uMRD to Ibr (n=31) or Ibr + Ven (n=32). Median overall follow-up was 38.2 mo (range, 15.0-47.9); median post-randomization follow-up was 24.0 mo (range, 5.8-33.1). In pts with Confirmed uMRD randomized to placebo versus Ibr, no new DFS events occurred since the primary analysis; 2-year DFS rates post-randomization remained unchanged at 95% (placebo) vs 100% (Ibr), for a 4.7% difference (95% CI -1.6-10.9) and overall log-rank P=0.1573 (Figure 1). In the placebo and Ibr arms post-randomization, modest improvements were observed in complete response (CR) rates, including CR with incomplete bone marrow recovery (CRi) (Figure 2). Estimated 36-mo PFS rates were 95% with placebo and 100% with Ibr. In pts without Confirmed uMRD randomized to Ibr vs Ibr + Ven, greater improvements in best uMRD rates and CR/CRi rates were observed with Ibr + Ven than with Ibr post-randomization (Figure 2). Estimated 36-mo PFS rates were 97% with both Ibr and Ibr + Ven. Median treatment duration was 36.8 mo (range, 0.5-47.9) in all pts (N=164). Modest differences in AEs were observed across treatment arms post-randomization. During the overall study period across all-treated pts, the most frequent grade 3/4 AEs were neutropenia (36%), hypertension (10%), thrombocytopenia (5%), and diarrhea (5%). With up to 48 mo of treatment, AEs led to discontinuation of Ibr or Ven in 13% of pts; no new safety signals emerged. Conclusions : First-line Ibr + Ven is an all-oral, once-daily, chemotherapy-free regimen that provides deep responses in pts with CLL. With an additional year of follow-up and no new MRD relapses, PDs or deaths in pts with confirmed uMRD, the 2-year DFS rate in the MRD-guided placebo arm remained high at 95% while 3-year PFS rates were ≥95% across all randomized treatment arms. The results in pts with Confirmed uMRD support the potential for treatment-free remission with fixed-duration treatment, including in pts with high-risk features. High rates of uMRD were achieved; the safety profile of Ibr + Ven was consistent with known safety profile for each agent. Figure 1 Figure 1. Disclosures Ghia: Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Sunesis: Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding. Allan: Celegene: Research Funding; AstraZeneca Pharmaceuticals LP, Genentech, a member of the Roche Group, Janssen Biotech Inc, TG Therapeutics Inc.: Research Funding; AbbVie: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria; Genentech: Consultancy, Research Funding; TG Therapeutics: Research Funding; Epizyme: Consultancy; AbbVie Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Janssen Biotech Inc, Pharmacyclics LLC: Consultancy; AbbVie Inc, Ascentage Pharma, Epizyme, Genentech, a member of the Roche Group, Janssen Biotech Inc, Pharmacyclics LLC: Other: Advisory Committee. Siddiqi: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Juno therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Other: DSM Member, Speakers Bureau; PCYC: Speakers Bureau; Jannsen: Speakers Bureau; Dava Oncology: Honoraria; ResearchToPractice: Honoraria. Kipps: Janssen: Consultancy, Honoraria, Other, Research Funding, Speakers Bureau; Roche: Honoraria, Other; MD Anderson Cancer Center: Research Funding; Velos: Research Funding; CRIM: Research Funding; Indy Hematology Review: Other; TG Therapeutics: Other; Verstem: Other, Speakers Bureau; University of California, San Diego: Current Employment; Pharmacyclics/AbbVie: Honoraria, Research Funding; Breast Cancer Research Foundation: Research Funding; SCOR - The Leukemia and Lymphoma Society: Research Funding; National Cancer Institute/NIH: Honoraria, Research Funding; Genentech/Roche: Honoraria; European Research Initiative on CLL (ERIC): Honoraria; Bionest Partner: Other; Celgene: Consultancy, Honoraria, Other, Research Funding; Genetech: Honoraria, Other; Genentech-Roche: Consultancy; Gilead Sciences: Consultancy, Honoraria, Other, Speakers Bureau; DAVA Pharmaceuticals: Speakers Bureau; DAVAOncology: Consultancy, Honoraria, Other; AbbVie: Consultancy, Honoraria, Other, Speakers Bureau; Oncternal Therapeutics, Inc.: Current holder of stock options in a privately-held company, Other: Stock or other ownership, Patents & Royalties: Cirmtuzumab was developed by Thomas J. Kipps in the Thomas J. Kipps laboratory and licensed by the University of California to Oncternal Therapeutics, Inc., which provided stock options and research funding to the Thomas J. Kipps laboratory., Research Funding; Moores Cancer Center: Current Employment; MedImmune Inc: Research Funding; GlaxoSmithKline: Research Funding; Gilead Sciences, Inc.: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding, Speakers Bureau; Pharmacyclics LLC, an Abbvie Company: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Research Funding; Abbott Laboratories: Consultancy, Research Funding. Kuss: Commonwealth Serum Laboratories: Other: Stock or other ownership; AbbVie: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Merck: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Kyowa Kirin: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria; Roche Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Janssen: Speakers Bureau. Opat: AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sandoz: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; CSL: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Monash Health: Current Employment; BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GIlead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding. Flinn: Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Badoux: Janssen: Honoraria; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses. Tedeschi: Beigene: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau. Gonzalez-Barca: Kiowa: Consultancy, Speakers Bureau; Eusapharma: Consultancy; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Takeda: Speakers Bureau; Roche: Other: Travel, Accommodations, Expenses; AbbVie: Other: Travel, Accommodations, Expenses, Speakers Bureau. Pagel: Pharmacyclics/AbbVie: Consultancy; Gilead: Consultancy; Actinium Pharmaceuticals: Consultancy; Kite, a Gilead Company: Consultancy; BeiGene: Consultancy; Epizyme: Consultancy; MEI Pharma: Consultancy; AstraZeneca: Consultancy; Incyte/MorphoSys: Consultancy. Jacobs: AstraZeneca: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy; Adaptive Biotechnologies: Consultancy; MEI Pharma: Research Funding; TeneoBio: Research Funding; SecuraBio: Consultancy, Speakers Bureau; Verastem: Consultancy; TG Therapeutics: Research Funding, Speakers Bureau; Jannsen: Speakers Bureau; Genentech: Consultancy; AbbVie: Consultancy, Speakers Bureau. Szafer-Glusman: AbbVie: Current Employment, Other: Stock or other ownership. Zhou: AbbVie: Current Employment, Other: Stock and other ownership. Ninomoto: AbbVie: Current Employment, Other: Stock or other ownership. Dean: Pharmacyclics: Current Employment, Other: Stock or other ownership; AbbVie: Other: Stock Ownership. Tam: Pharmacyclics: Honoraria; BeiGene: Consultancy, Honoraria; Loxo: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Wierda: Janssen: Research Funding; AstraZeneca: Research Funding; GSK/Novartis: Research Funding; Acerta Pharma Inc.: Research Funding; Karyopharm: Research Funding; Xencor: Research Funding; Oncternal Therapeutics, Inc.: Research Funding; Loxo Oncology, Inc.: Research Funding; Genentech: Research Funding; Sunesis: Research Funding; Miragen: Research Funding; Cyclacel: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Juno Therapeutics: Research Funding; Gilead Sciences: Research Funding; KITE Pharma: Research Funding; Genzyme Corporation: Consultancy; AbbVie: Research Funding. OffLabel Disclosure: Ibrutinib in combination with venetoclax is not approved in any indication.

Background: Umbralisib is an oral, once-daily, novel, dual inhibitor of phosphatidylinositol-3-kinase-delta (PI3Kδ) and casein kinase-1ε (CK1ε) that exhibits improved selectivity for the delta isoform of PI3K. Ublituximab is a novel anti-CD20 monoclonal antibody glycoengineered for enhanced antibody-dependent cellular cytotoxicity that targets a unique epitope on CD20. U2 has been well-tolerated and demonstrated promising activity in heavily pre-treated CLL patients. Herein, results are presented for the randomized, multicenter, Phase 3 UNITY-CLL trial (NCT02612311), which evaluated U2 vs O+Chl in patients with TN and R/R CLL. Methods: Patients ≥18 years of age with treatment-naïve (TN) or relapsed/refractory (R/R) CLL requiring treatment per iwCLL criteria with adequate organ function and ECOG PS ≤2 were eligible. Stratification factors included treatment status (TN vs R/R) and del(17p) status. Patients were initially randomized 1:1:1:1 to receive U2, O+Chl, umbralisib monotherapy, or ublituximab monotherapy. Following establishment of contribution comparing U2 to the single agents, patients were randomized 1:1 to U2 or O+Chl. Umbralisib was given orally at 800 mg once-daily until progression or removal from treatment for other reasons. Ublituximab was administered intravenously at 900 mg on Days 1/2 [split 150/750 mg], 8, and 15 of Cycle 1, Day 1 of Cycles 2 - 6, and on Day 1 every 3 cycles after Cycle 6. O was given intravenously at 1000 mg on Days 1/2 [split 100/900], 8, and 15 of Cycle 1, and Day 1 of Cycles 2 - 6. Chl was given orally at 0.5 mg/kg on Day 1 and 15 of Cycles 1 - 6. Each cycle was 28 days. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS) of U2 vs O+Chl. Key secondary endpoints included IRC-assessed overall response rate (ORR), complete response (CR), undetectable minimal residual disease (uMRD), duration of response (DOR), and safety (assessed from the first dose until 30 days after the last dose of study medication in each arm) as well as contribution of umbralisib and ublituximab to the U2 combination. Results: From Feb 2016 - Oct 2017, 421 pts were randomized to the U2 (n=210) or O+Chl (n=211) arms. The median age was 67 y (range, 36-91); 57% of patients (n=240) were treatment-naïve; 43% (n=181) had R/R CLL (median number of prior treatments = 1); 10% had del(17p), 20% del(11q), and 56% were IgHV unmutated. 66% were male. Demographics were well-balanced between treatment arms. At a median follow-up of 36.2 mos, U2 significantly prolonged PFS vs O+Chl (median 31.9 mos vs 17.9 mos; HR 0.546, 95% CI 0.413-0.720, P&lt;0.0001; Figure 1). Estimated 24-mo PFS rates with U2 and O+Chl were 60.8% and 40.4%, respectively. PFS improvement with U2 vs O+Chl was consistent across all subgroups examined including treatment naïve patients (median 38.5 mos vs 26.1 mos; HR [95% CI]; 0.482 [0.316-0.736]); and relapsed/refractory patients (median 19.5 mos vs 12.9 mos; HR [95% CI]; 0.601 [0.415-0.869]). IRC-assessed ORR was higher with U2 (83.3%; 95% CI, 78.1%-88.6%) vs O+Chl (68.7%; 95% CI, 62.2%-75.2%; P&lt;0.001). Among previously treated subjects, twenty-six (6%) received prior ibrutinib (14 on U2, 12 on O+Chl), with an ORR of 57% observed for U2 compared to 25% for O+Chl in this population. MRD data is currently being analyzed. The median treatment duration was 23 mos for U2 (range, 0.1 - 49 mos) and 5 mos (range, 0.1 - 7 mos) for O+Chl. G3/4 AEs of interest regardless of causality (U2 vs O+Chl) included neutropenia (30.6% vs 34.7%), thrombocytopenia (3.4% vs 13.1%), diarrhea (12.1% vs 2.5%), infusion related reaction (1.9% vs 3.5%), elevated AST/ALTs (8.3% vs 2%), colitis (3.4% vs 0%) and pneumonitis (2.9% vs 0%). AEs led to treatment discontinuation in 34 patients (16.5%) on U2 and 16 patients (7.6%) on O+Chl. Conclusions: UNITY-CLL is the first randomized Phase 3 study in CLL of a PI3Ki vs. chemoimmunotherapy, and the first randomized study of a PI3Ki in treatment-naive CLL. U2 exhibited a well-tolerated safety profile, and significantly improved PFS vs. standard of care chemoimmunotherapy in patients with treatment-naive and relapsed/refractory CLL. Figure Disclosures Gribben: Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Celgene: Research Funding; Abbvie: Honoraria. Jurczak:Celgene: Research Funding; Afimed: Research Funding; Sandoz-Novartis: Consultancy; European Medicines Agency,: Consultancy; AstraZeneca: Consultancy; Takeda: Research Funding; Janssen China R&D: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Bayer: Research Funding; Acerta: Consultancy, Research Funding; Pharmacyclics: Research Funding; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; MEI Pharma: Research Funding; Nordic Nanovector: Research Funding; Servier: Research Funding; Merck: Research Funding; Gilead Sciences: Research Funding; Epizyme: Consultancy; Roche: Research Funding; MorphoSys: Research Funding; TG Therapeutics, Inc.: Research Funding; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months. Jacobs:Sanofi Genzyme: Speakers Bureau; Genentech: Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Verastem: Consultancy; Seattle Genetics: Consultancy; Astra Zeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; TG Therapeutics, Inc.: Research Funding. Giannopoulos:BMS-Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Janssen: Honoraria. Wrobel:Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau. Zafar:Bristol Meyers Squibb: Honoraria, Other: TRAVEL, ACCOMODATIONS, EXPENSES (paid by any for-profit health care company); Florida Cancer Specialists and Research Institute: Current Employment; Sarah Canon Research Institute: Research Funding; Karyopharm: Honoraria; AstraZeneca: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Danilov:Nurix: Consultancy; Celgene: Consultancy; Astra Zeneca: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Gilead Sciences: Research Funding; Verastem Oncology: Consultancy, Research Funding; Pharmacyclics: Consultancy; Abbvie: Consultancy; BeiGene: Consultancy; Takeda Oncology: Research Funding; Karyopharm: Consultancy; TG Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; Rigel Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Research Funding; Bayer Oncology: Consultancy, Research Funding. Burke:Gilead: Consultancy; Epizyme: Consultancy; Adaptive: Consultancy; Kura: Consultancy; Astra Zeneca: Consultancy; Bayer: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy; Morphosys: Consultancy; Verastem: Consultancy; Roche: Consultancy; Seattle Genetics: Speakers Bureau; Celgene: Consultancy. Goldschmidt:Bristol-Myers Squibb: Speakers Bureau; Amgen: Consultancy; Blue Ridge Cancer Care: Current Employment. Huntington:Genentech: Consultancy; Astrazeneca: Honoraria; TG Therapeutics: Research Funding; Pharmacyclics: Honoraria; Novartis: Consultancy; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; AbbVie: Consultancy; DTRM: Research Funding. Pinilla Ibarz:AstraZeneca: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Novartis: Consultancy; Sunesis Pharmaceuticals: Consultancy; TG Therapeutics: Consultancy; Sanofi: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Sharman:Bristol Meyers Squibb: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; BeiGene: Research Funding. Siddiqi:AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Juno: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Oncternal: Research Funding; TG Therapeutics: Research Funding; Janssen: Speakers Bureau; Seattle Genetics: Speakers Bureau. Brander:MEI Pharma: Other, Research Funding; Pfizer: Consultancy, Other; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Tolero: Research Funding; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; NCCN: Other; Verastem: Consultancy, Honoraria, Other, Research Funding; Teva: Consultancy, Honoraria; Novartis: Consultancy, Other; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; NCCN: Other; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding. Kolibaba:TG Therapeutics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Sumitomo Dainippon Pharma Oncology: Consultancy, Other; Verastem: Honoraria; Genentech: Research Funding; Gilead: Research Funding; Janssen: Research Funding; McKesson Life Sciences: Consultancy; Novartis: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Atara Biotech: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Cell Therapeutics: Research Funding; Compass Oncology: Ended employment in the past 24 months. Ghosh:Karyopharm: Consultancy; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol-Myers Squibb: Speakers Bureau; Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Kite/Gilead: Consultancy, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Roche/Genentech: Research Funding. Sportelli:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Miskin:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. O'Connor:Astex Pharmaceuticals: Honoraria, Research Funding; Celgene: Honoraria, Other: Data Safety Monitoring Committee, Research Funding; TG Therapeutics: Current Employment, Current equity holder in publicly-traded company; Kymera Therapeutics: Current equity holder in private company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nomocan: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Mundipharma: Other: Consulting; Servier: Consultancy. Weiss:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Flinn:Iksuda Therapeutics: Consultancy; Curis: Research Funding; Infinity Pharmaceuticals: Research Funding; F. Hoffmann-La Roche: Research Funding; Vincera Pharma: Consultancy; Karyopharm Therapeutics: Research Funding; Gilead Sciences: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Triphase Research & Development Corp.: Research Funding; Trillium Therapeutics: Research Funding; TG Therapeutics: Consultancy, Research Funding; Teva: Research Funding; Seattle Genetics: Consultancy, Research Funding; ArQule: Research Funding; Unum Therapeutics: Consultancy, Research Funding; Incyte: Research Funding; Forma Therapeutics: Research Funding; Loxo: Research Funding; BeiGene: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Forty Seven: Research Funding; Genentech, Inc.: Research Funding; Great Point Partners: Consultancy; IGM Biosciences: Research Funding; Juno Therapeutics: Consultancy, Research Funding; Acerta Pharma: Research Funding; AbbVie: Consultancy, Research Funding; Celgene: Research Funding; Johnson & Johnson: Other; Yingli Pharmaceuticals ≠: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Roche: Consultancy, Research Funding; Curio Science: Consultancy; Nurix Therapeutics: Consultancy; Takeda: Consultancy, Research Funding; Calithera Biosciences: Research Funding; Merck: Research Funding; Constellation Pharmaceuticals: Research Funding; Agios: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Pfizer: Research Funding; Novartis: Research Funding.

Abstract Background: Resistance to venetoclax, a BCL2 inhibitor, has been shown to be mediated by co-expression of other BCL2 proteins including BCLXL and MCL1 in relapsed/refractory AML (R/R AML). Therapeutic agents reducing resistance to BCL2 inhibitors and exhibiting anti-tumor activity could synergize with venetoclax to increase response rates further. One approach to enhance the potency of venetoclax is through combination with targeted radiotherapy. Studies in tumor cells have shown that DNA damage reduces the level of MCL1, a known mediator of venetoclax resistance. The monoclonal antibody radioconjugate, lintuzumab-Ac225, is a highly cytotoxic alpha-radiation emitter that selectively targets CD33, a cell surface antigen expressed on majority of AML cells. The high-energy alpha-particle emissions from lintuzumab-Ac225 as a single agent elicits single and double-strand DNA breaks in targeted tumor cells as demonstrated from prior clinical studies. (ASH 2017, 2018). In venetoclax-resistant cell lines in vitro, lintuzumab-Ac225 promotes MCL1 degradation through DNA damage resulting in increased cell sensitivity to venetoclax. Similarly, mouse xenograft models with venetoclax-resistant AML tumor lines demonstrated tumor regression and increased survival in mice receiving both venetoclax and lintuzumab-Ac225. The aims of this phase I/II study are to assess the safety, tolerability and efficacy of lintuzumab-Ac225 in combination with venetoclax in R/R AML. Study Design: The Phase I portion of the study uses a 3+3 dose-escalation design to determine the maximum tolerated dose (MTD) of lintuzumab-Ac225 when given in combination with venetoclax. The dose levels for lintuzumab-Ac225 are 0.5, 0.75, and 1.0 µCi/kg. The Phase II portion of the study will enroll up to an additional 20 patients and treat with the recommended phase II dose (RP2D) with venetoclax to determine the best overall response (CR+CRh+CRi) up to 6 months after starting treatment. Eligible patients include R/R-AML patients aged 18 years and older with adequate organ function, ECOG Performance Status 0-2, and more than 25% CD33 positive of leukemic blasts by flow cytometry. Patients with antecedent MDS, MPNs, or therapy-related AML are eligible. During Cycle 1, venetoclax dosing will be ramped up during the first 4 days in order to minimize the risk of tumor lysis syndrome (TLS). After Cycle 1, all patients will receive venetoclax at 400 mg/day PO on Days 1 to 21 of each cycle. Lintuzumab-Ac225 is administered as a single dose on Day 5 of each cycle. Results: Ten R/R AML patients were treated with lintuzumab-Ac225 at 0.5 µCi/kg (n=3), 0.75 µCi/kg (n=6) and 1.0 µCi/kg (n=1) in combination with venetoclax in the phase I dose escalation portion as of 1-August-2021. The median age was 67 years (range 49-83) with 5/10 (50%) refractory; 8/10 (80%) had unfavorable risk (ELN). Three patients were enrolled on the first cohort at dose level 0.5 µCi/kg of lintuzumab-Ac225 and showed clinically acceptable safety profile with no DLTs. In addition, one patient achieved CRi at the end of cycle 1. Results from the first cohort were encouraging and acceptable for dose escalation. An intermediate Cohort 2B at dose level 0.75 µCi/kg, was implemented. To date, 6 patients were enrolled on cohort 2B, and based on the Safety Committee recommendation, dose level at 1.0 µCi/kg may be resumed. In preliminary data on all patients, lintuzumab-Ac225 treatment-related grades 3/4 adverse events (AEs) include hematologic AEs and only one count of non-hematologic event (hyponatremia) (Table 1). There were no early deaths (≤30d) in any cohort. Overall, lintuzumab-Ac225 can be combined with venetoclax with a manageable toxicity profile. While sample size is limited, ORR (CR/CRi) for all R/R AML patients and TP53-mutant R/R patients were 20% (2/10) and 67% (2/3), respectively. Updated safety and response data will be presented at ASH2021. Conclusion: Combining lintuzumab-Ac225 with venetoclax in patients with R/R AML has an acceptable clinical safety profile with 0% 30-day mortality rate. 67% ORR is particularly encouraging in TP53-mutant R/R AML. These data support the further evaluation of lintuzumab-Ac225 in combination with venetoclax in patients with R/R AML, especially in TP53-mutant R/R patients. Figure 1 Figure 1. Disclosures Schiller: FujiFilm: Research Funding; Forma: Research Funding; Arog: Research Funding; Gamida Cell Ltd.: Research Funding; Karyopharm: Research Funding; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; Geron: Research Funding; Mateon: Research Funding; Onconova: Research Funding; Pfizer: Current equity holder in publicly-traded company, Research Funding; PrECOG: Research Funding; Regimmune: Research Funding; Delta-Fly: Research Funding; Actinium Pharmaceuticals, Inc: Research Funding; Actuate: Research Funding; Samus: Research Funding; Constellation Pharmaceuticals: Research Funding; Deciphera: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Research Funding; Takeda: Research Funding; Stemline Therapeutics, Inc.: Honoraria, Research Funding, Speakers Bureau; Sangamo: Research Funding; Genentech-Roche: Research Funding; Celator: Research Funding; BMS/Celgene: Consultancy, Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Astellas: Honoraria, Research Funding, Speakers Bureau; Trovagene: Research Funding; Tolero: Research Funding; Daiichi-Sankyo: Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Honoraria, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Elevate: Research Funding; Bio: Research Funding; Ono-UK: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Pharma: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Biomed Valley Discoveries: Research Funding; Eli Lilly: Research Funding; ASH foundation: Other: Chair-unpaid; Sellas: Research Funding; Ono: Consultancy; Incyte: Consultancy; Ariad: Research Funding; AstraZeneca: Consultancy; Kaiser Permanente: Consultancy; Cyclacel: Research Funding; MedImmune: Research Funding; Ambit: Research Funding; Leukemia & Lymphoma Society: Research Funding; Bluebird Bio: Research Funding; Boehringer-Ingleheim: Research Funding; Cellerant: Research Funding; CTI Biopharma: Research Funding; Janssen: Research Funding; Kura Oncology: Research Funding; Pharmacyclics: Honoraria, Speakers Bureau; Millennium: Research Funding; National Marrow Donor Program: Research Funding; NIH: Research Funding; Onyx: Research Funding; Pharmamar: Research Funding; UC Davis: Research Funding; UCSD: Research Funding; Evidera: Consultancy; NCI: Consultancy; Novartis: Speakers Bureau. Finn: Jazz: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; BeiGene: Consultancy, Speakers Bureau; ADC Therapeutics: Consultancy, Speakers Bureau. Roboz: Mesoblast: Consultancy; Jazz: Consultancy; Astellas: Consultancy; Janssen: Consultancy; Actinium: Consultancy; Blueprint Medicines: Consultancy; Jasper Therapeutics: Consultancy; Daiichi Sankyo: Consultancy; Celgene: Consultancy; Glaxo SmithKline: Consultancy; Bayer: Consultancy; AbbVie: Consultancy; AstraZeneca: Consultancy; Amgen: Consultancy; Astex: Consultancy; Helsinn: Consultancy; MEI Pharma - IDMC Chair: Consultancy; Agios: Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Otsuka: Consultancy; Janssen: Research Funding; Pfizer: Consultancy; Roche/Genentech: Consultancy. Orozco: Actinium Pharmaceuticals, Inc.: Other: site PI for clinical trial(s) sponsored by Actinium, Research Funding. Lin: Actinium Pharmaceuticals, Inc.: Current Employment. Chen: Actinium Pharmaceuticals, Inc.: Current Employment, Current equity holder in publicly-traded company. OffLabel Disclosure: Venetoclax use in relapsed-refractory AML

P-BCMA-101 is a novel chimeric antigen receptor (CAR)-T cell product targeting B Cell Maturation Antigen (BCMA). P-BCMA-101 is produced using the piggyBac® (PB) DNA Modification System instead of the viral vector that is used with most CAR-T cells, requiring only plasmid DNA and mRNA. This makes it less costly and produces cells with a high percentage of the favorable T stem cell memory phenotype (TSCM). The higher cargo capacity of PB permits the incorporation of multiple genes in addition to CAR(s), including a safety switch allowing for rapid CAR-T cell elimination with a small molecule drug infusion in patients if desired, and a selection gene allowing for enrichment of CAR+ cells. Rather than using a traditional antibody-based binder, P-BCMA-101 has a Centyrin™ fused to a CD3ζ/4-1BB signaling domain. Centyrins are fully human proteins with high specificity and a large range of binding affinities, but are smaller, more stable and potentially less immunogenic than traditional scFv. Cumulatively, these features are predicted to result in a greater therapeutic index. A Phase 1, 3+3 dose escalation from 0.75 to 15 x 106 P-BCMA-101 CAR-T cells/kg (RP2D 6-15 x 106 cells/kg) was conducted in patients with r/r MM (Blood 2018 132:1012) demonstrating excellent efficacy and safety of P-BCMA-101, including notably low rates and grades of CRS and neurotoxicity (maximum Grade 2 without necessitating ICU admission, safety switch activation or other aggressive measures). These results supported FDA RMAT designation and initiation of a pivotal Phase 2 study. A Phase 2 pivotal portion of this study has recently been designed and initiated (PRIME; NCT03288493) in r/r MM patients who have received at least 3 prior lines of therapy. Their therapy must have contained a proteasome inhibitor, an IMiD, and CD38 targeted therapy with at least 2 of the prior lines in the form of triplet combinations. They must also have undergone ≥2 cycles of each line unless PD was the best response, refractory to the most recent line of therapy, and undergone autologous stem cell transplant or not be a candidate. Patients are required to be >=18 years old, have measurable disease by International Myeloma Working Group criteria (IMWG; Kumar 2016), adequate vital organ function and lack significant autoimmune, CNS and infectious diseases. No pre-specified level of BCMA expression is required, as this has not been demonstrated to correlate with clinical outcomes for P-BCMA-101 and other BCMA-targeted CAR-T products. Interestingly, unlike most CAR-T products patients may receive P-BCMA-101 after prior CAR-T cells or BCMA targeted agents, and may be multiply infused with P-BCMA-101. Patients are apheresed to harvest T cells, P-BCMA-101 is then manufactured and administered to patients as a single intravenous (IV) dose (6-15 x 106 P-BCMA-101 CAR-T cells/kg) after a standard 3-day cyclophosphamide (300 mg/m2/day) / fludarabine (30 mg/m2/day) conditioning regimen. One hundred patients are planned to be treated with P-BCMA-101. Uniquely, given the safety profile demonstrated during Phase 1, no hospital admission is required and patients may be administered P-BCMA-101 in an outpatient setting. The primary endpoints are safety and response rate by IMWG criteria. With a 100-subject sample, the Phase 2 part of the trial will have 90% power to detect a 15-percentage point improvement over a 30% response rate (based on that of the recently approved anti-CD38 antibody daratumumab), using an exact test for a binomial proportion with a 1-sided 0.05 significance level. Multiple biomarkers are being assessed including BCMA and cytokine levels, CAR-T cell kinetics, immunogenicity, T cell receptor diversity, CAR-T cell and patient gene expression (e.g. Nanostring) and others. Overall, the PRIME study is the first pivotal study of the unique P-BCMA-101 CAR-T product, and utilizes a number of novel design features. Studies are being initiated in combination with approved therapeutics and earlier lines of therapy with the intent of conducting Phase 3 trials. Funding by Poseida Therapeutics and the California Institute for Regenerative Medicine (CIRM). Disclosures Costello: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Gregory:Poseida: Research Funding; Celgene: Speakers Bureau; Takeda: Speakers Bureau; Amgen: Speakers Bureau. Ali:Celgene: Research Funding; Poseida: Research Funding. Berdeja:Amgen Inc, BioClinica, Celgene Corporation, CRISPR Therapeutics, Bristol-Myers Squibb Company, Janssen Biotech Inc, Karyopharm Therapeutics, Kite Pharma Inc, Prothena, Servier, Takeda Oncology: Consultancy; AbbVie Inc, Amgen Inc, Acetylon Pharmaceuticals Inc, Bluebird Bio, Bristol-Myers Squibb Company, Celgene Corporation, Constellation Pharma, Curis Inc, Genentech, Glenmark Pharmaceuticals, Janssen Biotech Inc, Kesios Therapeutics, Lilly, Novartis, Poseida: Research Funding; Poseida: Research Funding. Patel:Oncopeptides, Nektar, Precision Biosciences, BMS: Consultancy; Takeda, Celgene, Janssen: Consultancy, Research Funding; Poseida Therapeutics, Cellectis, Abbvie: Research Funding. Shah:University of California, San Francisco: Employment; Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; Indapta Therapeutics: Equity Ownership; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding; Poseida: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ostertag:Poseida Therapeutics, Inc.: Employment, Equity Ownership. Martin:Poseida Therapeutics, Inc.: Employment, Equity Ownership. Ghoddusi:Poseida Therapeutics, Inc.: Employment, Equity Ownership. Shedlock:Poseida Therapeutics, Inc.: Employment, Equity Ownership. Spear:Poseida Therapeutics, Inc.: Employment, Equity Ownership. Orlowski:Poseida Therapeutics, Inc.: Research Funding. Cohen:Poseida Therapeutics, Inc.: Research Funding.

Abstract Introduction: Lenalidomide is currently approved by the FDA for treatment of transfusion-dependent, lower risk, deletion 5q (del(5q)) MDS patients. In practice, lenalidomide is often used for treatment of non-del(5q) anemic, lower risk MDS patients as endorsed by national guidelines. The risk of AML transformation among non-del(5q) MDS patients treated with lenalidomide has not been well studied, nor among del(5q) MDS patients outside the context of original clinical trials. We conducted a retrospective cohort study of 1,248 MDS patients treated with or without lenalidomide at the Moffitt Cancer Center (MCC) to investigate the association between lenalidomide and AML transformation. Methods: Patients treated for MDS at MCC in 2004-2012 were identified through MCC's data warehouse, including data from the Cancer Registry, electronic medical records and disease-specific databases. A total of 1,248 MDS patients, ages 18+ years, were identified, corresponding to International Classification of Diseases for Oncology Third Edition (ICD-O-3) codes 99801, 99803, 99833, 99843, 99853, 99863, 99873, 99891 and 99893. A total of 150 cases of AML transformation were verified by two hematologists confirming the MDS diagnosis and AML transformation. Incidence rates and 95% confidence intervals (CI) for AML transformation were estimated based on the Poisson distribution. Cox proportional hazards ratios (HR) and 95% CIs were calculated to estimate age-adjusted associations between lenalidomide treatment and AML transformation in the overall cohort, and stratified by lower (low and intermediate-1) risk versus higher (intermediate-2 and high) risk IPSS. To obtain additional details on lenalidomide treatment and potential confounders, medical chart abstraction was conducted for all AML cases and a sample of MDS patients from the baseline cohort who had not developed AML; these controls were matched to cases 1:1 on age at MDS diagnosis (<60 versus 60+ years), gender, follow-up time (+/- 6 months), date of diagnosis, (+/- 1 year), lower versus higher risk IPSS, and presence or absence of del (5q). Based on the abstracted data for the nested case-control sample, associations between lenalidomide and AML transformation were adjusted for cytogenetic risk, use of erythroid-stimulating agents (ESA), percent bone marrow myeloblasts, and MDS histology. Results: Overall, 1,248 MDS patients were followed for an average of 30 months, including patients treated with (n=210) or without (n=1,038) lenalidomide. AML transformation was observed among 16 patients treated with lenalidomide (2.4 per 100 person-years) and 134 patients treated without lenalidomide (5.5 per 100 person-years), corresponding to an age-adjusted HR of 0.44 (95% CI=0.26-0.74). Only two of the 150 MDS patients who transformed to AML had MDS del(5q). When stratified by IPSS, there was no increased risk of AML transformation associated with lenalidomide among patients with lower risk IPSS (HR=0.27, 95% CI=0.12-0.64) or patients with higher risk IPSS (HR=0.99, 95% CI=0.51-1.93). Based on the nested case-control analysis, 16.0% and 20.7% of MDS-AML cases and matched MDS controls who did not develop AML were treated with lenalidomide, respectively, corresponding to an adjusted odds ratio (OR) of 1.16 (95% CI=0.52-2.56). Although a significant interaction was noted between lenalidomide and IPSS in relation to AML in the cohort analysis (Figure 1), lenalidomide was not associated with AML transformation among lower risk (OR=0.44, 95% CI=0.10-1.94) or higher risk (OR=2.06, 95% CI=0.69-6.18) MDS patients after adjustment for prognostic factors in the case-control analysis. Conclusion: To our knowledge, this study represents the largest cohort investigated outside the context of clinical trials for the rate of AML transformation among MDS patients treated with lenalidomide and the first to specifically examine non-del(5q) patients. Lenalidomide treatment was not associated with an increased risk of AML transformation among this large cohort of MDS patients. Figure 1: Incidence of acute myelogenous leukemia (AML) among myelodysplastic syndrome (MDS) patients treated with or without lenalidomide (Lena) and stratified by lower risk IPSS (low risk or intermediate-1 [0,1]) versus higher risk IPSS (intermediate-2 or high risk [2,3]), Moffitt Cancer Center, 2004-2012 Figure 1:. Incidence of acute myelogenous leukemia (AML) among myelodysplastic syndrome (MDS) patients treated with or without lenalidomide (Lena) and stratified by lower risk IPSS (low risk or intermediate-1 [0,1]) versus higher risk IPSS (intermediate-2 or high risk [2,3]), Moffitt Cancer Center, 2004-2012 Disclosures Rollison: Celgene, Inc.: Research Funding. Off Label Use: Lenalidomide given as treatment for non-del(5q) MDS and/or multiple myeloma . Shain:L&M Healthcare/Onyx/Amgen: Research Funding, Speakers Bureau; Envision/Celgene: Research Funding, Speakers Bureau. Lee:Celgene, Inc.: Research Funding. Hampras:Celgene, Inc: Research Funding. Fulp:Celgene, Inc.: Research Funding. Fisher:Celgene, Inc: Research Funding. Al Ali:Celgene, Inc: Research Funding. Padron:Icyte: Speakers Bureau; Novartis: Speakers Bureau. Lancet:Celgene, Inc: Consultancy, Research Funding. Xu:Celgene, Inc.: Employment, stock options Other. Knight:Celgene, Inc: Employment, stock options Other. List:Celgene, Inc.: Consultancy. Dalton:Genentech: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene, Inc.: Research Funding. Komrokji:Celgene: Consultancy, Research Funding.

The UP Manila Health Policy Development Hub recognizes the invaluable contribution of the participants in theseries of roundtable discussions listed below: RTD: Beyond Hospital Beds: Equity,quality, and service1. Ma. Esmeralda C. Silva, MPAf, MSPPM, PhD,Faculty, College of Public Health, UP Manila2. Leonardo R. Estacio, Jr., MCD, MPH, PhD, Dean,College of Arts and Sciences, UP Manila3. Michael Antonio F. Mendoza, DDM, MM, Faculty,College of Dentistry, UP Manila4. Hilton Y. Lam, MHA, PhD, Chair, UP Manila HealthPolicy Development Hub; Director, Institute of HealthPolicy and Development Studies, University of thePhilippines Manila5. Irma L. Asuncion, MHA, CESO III, Director IV,Bureau of Local Health Systems Development,Department of Health6. Renely Pangilinan-Tungol, MD, CFP, MPM-HSD,Municipal Health Officer, San Fernando, Pampanga7. Salome F. Arinduque, MD, Galing-Pook AwardeeRepresentative, Municipal Health Officer, San Felipe,Zambales8. Carmelita C. Canila, MD, MPH, Faculty, College ofPublic Health, University of the Philippines Manila9. Lester M. Tan, MD, MPH, Division Chief, Bureau ofLocal Health System Development, Department ofHealth10. Anthony Rosendo G. Faraon, MD, Vice President,Zuellig Family Foundation (ZFF)11. Albert Francis E. Domingo, MD, Consultant, HealthSystem strengthening through Public Policy andRegulation, World Health Organization12. Jesus Randy O. Cañal, MD, FPSO-HNS, AssociateDirector, Medical and Regulatory Affairs, AsianHospital and Medical Center13. Christian Edward L. Nuevo, Health Policy and SystemsResearch Fellow, Health Policy Development andPlanning Bureau, Department of Health14. Paolo Victor N. Medina, MD, Assistant Professor 4,College of Medicine, University of the PhilippinesManila15. Jose Rafael A. Marfori, MD, Special Assistant to theDirector, Philippine General Hospital16. Maria Teresa U. Bagaman, Committee Chair, PhilippineSociety for Quality, Inc.17. Maria Theresa G. Vera, MSc, MHA, CESO III, DirectorIV, Health Facility Development Bureau, Departmentof Health18. Ana Melissa F. Hilvano-Cabungcal, MD, AssistantAssociate Dean for Planning & Development, Collegeof Medicine, University of the Philippines Manila19. Fevi Rose C. Paro, Faculty, Department of Communityand Environmental Resource Planning, University ofthe Philippines Los Baños20. Maria Rosa C. Abad, MD, Medical Specialist III,Standard Development Division, Health Facilities andServices Regulation21. Yolanda R. Robles, RPh, PhD, Faculty, College ofPharmacy, University of the Philippines Manila22. Jaya P. Ebuen, RN, Development Manager Officer,CHDMM, Department of Health23. Josephine E. Cariaso, MA, RN, Assistant Professor,College of Nursing, University of the Philippines Manila24. Diana Van Daele, Programme Manager, CooperationSection, European Union25. Maria Paz de Sagun, Project Management Specialist,USAID26. Christopher Muñoz, Member, Yellow Warriors SocietyPhilippinesRTD: Health services and financingroles: Population based- andindividual-based1. Hilton Y. Lam, MHA, PhD, Chair, University of thePhilippines Manila Health Policy Development Hub;Director, Institute of Health Policy and DevelopmentStudies, University of the Philippines Manila2. Ma. Esmeralda C. Silva, MPAf, MSPPM, PhD,Faculty, College of Public Health, University of thePhilippines Manila3. Leonardo R. Estacio, Jr., MCD, MPH, PhD, Dean,College of Arts and Sciences, University of thePhilippines Manila4. Michael Antonio F. Mendoza, DDM, MM, Faculty,College of Dentistry, University of the PhilippinesManila5. Mario C. Villaverde, Undersecretary, Health Policyand Development Systems and Development Team,Department of Health6. Jaime Z. Galvez Tan, MD, Former Secretary, Department of Health7. Marvin C. Galvez, MD, OIC Division Chief, BenefitsDevelopment and Research Department, PhilippineHealth Insurance Corporation8. Alvin B. Caballes, MD, MPE, MPP, Faculty, Collegeof Medicine, University of the Philippines Manila9. Carlos D. Da Silva, Executive Director, Association ofMunicipal Health Maintenance Organization of thePhilippines, Inc.10. Anthony Rosendo G. Faraon, MD, Vice President,Zuellig Family Foundation (ZFF) 11. Albert Francis E. Domingo, MD, Consultant, HealthSystem strengthening through Public Policy andRegulation, World Health Organization12. Salome F. Arinduque, MD, Galing-Pook AwardeeRepresentative, Municipal Health Officer, San Felipe,Zambales13. Michael Ralph M. Abrigo, PhD, Research Fellow,Philippine Institute for Developmental Studies14. Oscar D. Tinio, MD, Committee Chair, Legislation,Philippine Medical Association15. Rogelio V. Dazo, Jr., MD, FPCOM, Legislation,Philippine Medical Association16. Ligaya V. Catadman, MM, Officer-in-charge, HealthPolicy Development and Planning Bureau, Department of Health17. Maria Fatima Garcia-Lorenzo, President, PhilippineAlliance of Patients Organization18. Tomasito P. Javate, Jr, Supervising Economic DevelopmentSpecialist, Health Nutrition and Population Division,National Economic and Development Authority19. Josefina Isidro-Lapena, MD, National Board ofDirector, Philippine Academy of Family Physicians20. Maria Eliza Ruiz-Aguila, MPhty, PhD, Dean, Collegeof Allied Medical Professions, University of thePhilippines Manila21. Ana Melissa F. Hilvano-Cabungcal, MD, AssistantAssociate Dean for Planning & Development, College ofMedicine, University of the Philippines Manila22. Maria Paz P. Corrales, MD, MHA, MPA, Director III,Department of Health-National Capital Region23. Karin Estepa Garcia, MD, Executive Secretary, PhilippineAcademy of Family Physicians24. Adeline A. Mesina, MD, Medical Specialist III,Philippine Health Insurance Corporation25. Glorey Ann P. Alde, RN, MPH, Research Fellow,Department of HealthRTD: Moving towards provincelevel integration throughUniversal Health Care Act1. Hilton Y. Lam, MHA, PhD, Chair, University of thePhilippines Manila Health Policy Development Hub;Director, Institute of Health Policy and DevelopmentStudies, University of the Philippines Manila2. Ma. Esmeralda C. Silva, MPAf, MSPPM, PhD,Faculty, College of Public Health, University of thePhilippines Manila3. Leonardo R. Estacio, Jr., MCD, MPH, PhD, Dean,College of Arts and Sciences, University of thePhilippines Manila4. Michael Antonio F. Mendoza, DDM, MM, Faculty,College of Dentistry, University of the PhilippinesManila5. Mario C. Villaverde, Undersecretary of Health, HealthPolicy and Development Systems and DevelopmentTeam, Department of Health6. Ferdinand A. Pecson, Undersecretary and ExecutiveDirector, Public Private Partnership Center7. Rosanna M. Buccahan, MD, Provincial Health Officer,Bataan Provincial Office8. Lester M. Tan, MD, Division Chief, Bureau of LocalHealth System Development, Department of Health9. Ernesto O. Domingo, MD, FPCP, FPSF, FormerChancellor, University of the Philippines Manila10. Albert Francis E. Domingo, MD, Consultant, HealthSystem strengthening through Public Policy andRegulation, World Health Organization11. Leslie Ann L. Luces, MD, Provincial Health Officer,Aklan12. Rene C. Catan, MD, Provincial Health Officer, Cebu13. Anthony Rosendo G. Faraon, MD, Vice President,Zuellig Family Foundation14. Jose Rafael A. Marfori, MD, Special Assistant to theDirector, Philippine General Hospital15. Jesus Randy O. Cañal, MD, FPSO-HNS, Consultant,Asian Hospital and Medical Center16. Ramon Paterno, MD, Member, Universal Health CareStudy Group, University of the Philippines Manila17. Mayor Eunice U. Babalcon, Mayor, Paranas, Samar18. Zorayda E. Leopando, MD, Former President,Philippine Academy of Family Physicians19. Madeleine de Rosas-Valera, MD, MScIH, SeniorTechnical Consultant, World Bank20. Arlene C. Sebastian, MD, Municipal Health Officer,Sta. Monica, Siargao Island, Mindanao21. Rizza Majella L. Herrera, MD, Acting Senior Manager,Accreditation Department, Philippine Health InsuranceCorporation22. Alvin B. Caballes, MD, MPE, MPP, Faculty, Collegeof Medicine, University of the Philippines Manila23. Pres. Policarpio B. Joves, MD, MPH, MOH, FPAFP,President, Philippine Academy of Family Physicians24. Leilanie A. Nicodemus, MD, Board of Director,Philippine Academy of Family Physicians25. Maria Paz P. Corrales, MD, MHA, MPA, Director III,National Capital Region Office, Department of Health26. Dir. Irma L. Asuncion, MD, MHA, CESO III, DirectorIV, Bureau of Local Health Systems Development,Department of Health27. Bernard B. Argamosa, MD, Mental Health Representative, National Center for Mental Health28. Flerida Chan, Chief, Poverty Reduction Section, JapanInternational Cooperation Agency29. Raul R. Alamis, Chief Health Program Officer, ServiceDelivery Network, Department of Health30. Mary Anne Milliscent B. Castro, Supervising HealthProgram Officer, Department of Health 31. Marikris Florenz N. Garcia, Project Manager, PublicPrivate Partnership Center32. Mary Grace G. Darunday, Supervising Budget andManagement Specialist, Budget and Management Bureaufor the Human Development Sector, Department ofBudget and Management33. Belinda Cater, Senior Budget and Management Specialist,Department of Budget and Management34. Sheryl N. Macalipay, LGU Officer IV, Bureau of LocalGovernment and Development, Department of Interiorand Local Government35. Kristel Faye M. Roderos, OTRP, Representative,College of Allied Medical Professions, University ofthe Philippines Manila36. Jeffrey I. Manalo, Director III, Policy Formulation,Project Evaluation and Monitoring Service, PublicPrivate Partnership Center37. Atty. Phebean Belle A. Ramos-Lacuna, Division Chief,Policy Formulation Division, Public Private PartnershipCenter38. Ricardo Benjamin D. Osorio, Planning Officer, PolicyFormulation, Project Evaluation and MonitoringService, Public Private Partnership Center39. Gladys Rabacal, Program Officer, Japan InternationalCooperation Agency40. Michael Angelo Baluyot, Nurse, Bataan Provincial Office41. Jonna Jane Javier Austria, Nurse, Bataan Provincial Office42. Heidee Buenaventura, MD, Associate Director, ZuelligFamily Foundation43. Dominique L. Monido, Policy Associate, Zuellig FamilyFoundation44. Rosa Nene De Lima-Estellana, RN, MD, Medical OfficerIII, Department of Interior and Local Government45. Ma Lourdes Sangalang-Yap, MD, FPCR, Medical OfficerIV, Department of Interior and Local Government46. Ana Melissa F. Hilvano-Cabungcal, MD, AssistantAssociate Dean for Planning & Development, College ofMedicine, University of the Philippines Manila47. Colleen T. Francisco, Representative, Department ofBudget and Management48. Kristine Galamgam, Representative, Department ofHealth49. Fides S. Basco, Officer-in-charge, Chief Budget andManagement Specialist, Development of Budget andManagementRTD: Health financing: Co-paymentsand Personnel1. Hilton Y. Lam, MHA, PhD, Chair, University of thePhilippines Manila Health Policy Development Hub;Director, Institute of Health Policy and DevelopmentStudies, University of the Philippines Manila2. Ma. Esmeralda C. Silva, MPAf, MSPPM, PhD,Faculty, College of Public Health, University of thePhilippines Manila3. Leonardo R. Estacio, Jr., MCD, MPH, PhD, Dean,College of Arts and Sciences, University of thePhilippines Manila4. Michael Antonio F. Mendoza, DDM, MM, Faculty,College of Dentistry, University of the Philippines Manila5. Ernesto O. Domingo, MD, Professor Emeritus,University of the Philippines Manila6. Irma L. Asuncion, MHA, CESO III, Director IV,Bureau of Local Health Systems Development,Department of Health7. Lester M. Tan, MD, MPH, Division Chief, Bureau ofLocal Health System Development, Department ofHealth8. Marvin C. Galvez, MD, OIC Division Chief, BenefitsDevelopment and Research Department, PhilippineHealth Insurance Corporation9. Adeline A. Mesina, MD, Medical Specialist III, BenefitsDepartment and Research Department, PhilippineHealth Insurance Corporation10. Carlos D. Da Silva, Executive Director, Association ofHealth Maintenance Organization of the Philippines,Inc.11. Ma. Margarita Lat-Luna, MD, Deputy Director, FiscalServices, Philippine General Hospital12. Waldemar V. Galindo, MD, Chief of Clinics, Ospital ngMaynila13. Albert Francis E. Domingo, MD, Consultant, HealthSystem strengthening through Public Policy andRegulation, World Health Organization14. Rogelio V. Dazo, Jr., MD, Member, Commission onLegislation, Philippine Medical Association15. Aileen R. Espina, MD, Board Member, PhilippineAcademy of Family Physicians16. Anthony R. Faraon, MD, Vice President, Zuellig FamilyFoundation17. Jesus Randy O. Cañal, Associate Director, Medical andRegulatory Affairs, Asian Hospital and Medical Center18. Jared Martin Clarianes, Technical Officer, Union of LocalAuthorities of the Philippines19. Leslie Ann L. Luces, MD, Provincial Health Officer,Aklan20. Rosa Nene De Lima-Estellana, MD, Medical OfficerIII, Department of the Interior and Local Government21. Ma. Lourdes Sangalang-Yap, MD, Medical Officer V,Department of the Interior and Local Government 22. Dominique L. Monido, Policy Associate, Zuellig FamilyFoundation23. Krisch Trine D. Ramos, MD, Medical Officer, PhilippineCharity Sweepstakes Office24. Larry R. Cedro, MD, Assistant General Manager, CharitySector, Philippine Charity Sweepstakes Office25. Margarita V. Hing, Officer in Charge, ManagementDivision, Financial Management Service Sector,Department of Health26. Dr. Carlo Irwin Panelo, Associate Professor, College ofMedicine, University of the Philippines Manila27. Dr. Angelita V. Larin, Faculty, College of Public Health,University of the Philippines Manila28. Dr. Abdel Jeffri A. Abdulla, Chair, RegionalizationProgram, University of the Philippines Manila29. Christopher S. Muñoz, Member, Philippine Alliance ofPatients Organization30. Gemma R. Macatangay, LGOO V, Department ofInterior and Local Government – Bureau of LocalGovernment Development31. Dr. Narisa Portia J. Sugay, Acting Vice President, QualityAssurance Group, Philippine Health InsuranceCorporation32. Maria Eliza R. Aguila, Dean, College of Allied MedicalProfessions, University of the Philippines Manila33. Angeli A. Comia, Manager, Zuellig Family Foundation34. Leo Alcantara, Union of Local Authorities of thePhilippines35. Dr. Zorayda E. Leopando, Former President, PhilippineAcademy of Family Physicians36. Dr. Emerito Jose Faraon, Faculty, College of PublicHealth, University of the Philippines Manila37. Dr. Carmelita C. Canila, Faculty, College of PublicHealth, University of the Philippines ManilaRTD: Moving towards third partyaccreditation for health facilities1. Hilton Y. Lam, MHA, PhD, Chair, University of thePhilippines Manila Health Policy Development Hub;Director, Institute of Health Policy and DevelopmentStudies, University of the Philippines Manila2. Ma. Esmeralda C. Silva, MPAf, MSPPM, PhD,Faculty, College of Public Health, University of thePhilippines Manila3. Leonardo R. Estacio, Jr., MCD, MPH, PhD, Dean,College of Arts and Sciences, University of thePhilippines Manila4. Michael Antonio F. Mendoza, DDM, MM, Faculty,College of Dentistry, University of the PhilippinesManila5. Rizza Majella L. Herrera, MD, Acting SeniorManager, Accreditation Department, Philippine HealthInsurance Corporation6. Bernadette C. Hogar-Manlapat, MD, FPBA, FPSA,FPSQua, MMPA, President and Board of Trustee,Philippine Society for Quality in Healthcare, Inc.7. Waldemar V. Galindo, MD, Chief of Clinics, Ospital ngMaynila8. Amor. F. Lahoz, Division Chief, Promotion andDocumentation Division, Department of Trade andIndustry – Philippine Accreditation Bureau9. Jenebert P. Opinion, Development Specialist, Department of Trade and Industry – Philippine AccreditationBureau10. Maria Linda G. Buhat, President, Association ofNursing Service Administrators of the Philippines, Inc.11. Bernardino A. Vicente, MD, FPPA, MHA, CESOIV, President, Philippine Tripartite Accreditation forHealth Facilities, Inc.12. Atty. Bu C. Castro, MD, Board Member, PhilippineHospital Association13. Cristina Lagao-Caalim, RN, MAN, MHA, ImmediatePast President and Board of Trustee, Philippine Societyfor Quality in Healthcare, Inc.14. Manuel E. Villegas Jr., MD, Vice Treasurer and Board ofTrustee, Philippine Society for Quality in Healthcare,Inc.15. Michelle A. Arban, Treasurer and Board of Trustee,Philippine Society for Quality in Healthcare, Inc.16. Joselito R. Chavez, MD, FPCP, FPCCP, FACCP,CESE, Deputy Executive Director, Medical Services,National Kidney and Transplant Institute17. Blesilda A. Gutierrez, CPA, MBA, Deputy ExecutiveDirector, Administrative Services, National Kidney andTransplant Institute18. Eulalia C. Magpusao, MD, Associate Director, Qualityand Patient Safety, St. Luke’s Medical Centre GlobalCity19. Clemencia D. Bondoc, MD, Auditor, Association ofMunicipal Health Officers of the Philippines20. Jesus Randy O. Cañal, MD, FPSO-HNS, AssociateDirector, Medical and Regulatory Affairs, Asian Hospitaland Medical Center21. Maria Fatima Garcia-Lorenzo, President, PhilippineAlliance of Patient Organizations22. Leilanie A. Nicodemus, MD, Board of Directors,Philippine Academy of Family Physicians23. Policarpio B. Joves Jr., MD, President, PhilippineAcademy of Family Physicians24. Kristel Faye Roderos, Faculty, College of Allied MedicalProfessions, University of the Philippines Manila25. Ana Melissa Hilvano-Cabungcal, MD, AssistantAssociate Dean, College of Medicine, University of thePhilippines Manila26. Christopher Malorre Calaquian, MD, Faculty, Collegeof Medicine, University of the Philippines Manila27. Emerito Jose C. Faraon, MD, Faculty, College ofPublic Health, University of the Philippines Manila 28. Carmelita Canila, Faculty, College of Public Health,University of the Philippines Manila29. Oscar D. Tinio, MD, Representative, Philippine MedicalAssociation30. Farrah Rocamora, Member, Philippine Society forQuality in Healthcare, IncRTD: RA 11036 (Mental Health Act):Addressing Mental Health Needs ofOverseas Filipino Workers1. Hilton Y. Lam, MHA, PhD, Chair, University of thePhilippines Manila Health Policy Development Hub;Director, Institute of Health Policy and DevelopmentStudies, University of the Philippines Manila2. Leonardo R. Estacio, Jr., MCD, MPH, PhD, UPManila Health Policy Development Hub; College ofArts and Sciences, UP Manila3. Ma. Esmeralda C. Silva, MPAf, MSPPM, PhD, UPManila Health Policy Development Hub; College ofPublic Health, UP Manila4. Michael Antonio F. Mendoza, DDM, UP ManilaHealth Policy Development Hub; College of Dentistry,UP Manila5. Frances Prescilla L. Cuevas, RN, MAN, Director,Essential Non-Communicable Diseases Division,Department of Health6. Maria Teresa D. De los Santos, Workers Education andMonitoring Division, Philippine Overseas EmploymentAdministration7. Andrelyn R. Gregorio, Policy Program and Development Office,Overseas Workers Welfare Administration8. Sally D. Bongalonta, MA, Institute of Family Life &Children Studies, Philippine Women’s University9. Consul Ferdinand P. Flores, Department of ForeignAffairs10. Jerome Alcantara, BLAS OPLE Policy Center andTraining Institute11. Andrea Luisa C. Anolin, Commission on FilipinoOverseas12. Bernard B. Argamosa, MD, DSBPP, National Centerfor Mental Health13. Agnes Joy L. Casino, MD, DSBPP, National Centerfor Mental Health14. Ryan Roberto E. Delos Reyes, Employment Promotionand Workers Welfare Division, Department of Laborand Employment15. Sheralee Bondad, Legal and International AffairsCluster, Department of Labor and Employment16. Rhodora A. Abano, Center for Migrant Advocacy17. Nina Evita Q. Guzman, Ugnayan at Tulong para saMaralitang Pamilya (UGAT) Foundation, Inc.18. Katrina S. Ching, Ugnayan at Tulong para sa MaralitangPamilya (UGAT) Foundation, Inc.RTD: (Bitter) Sweet Smile of Filipinos1. Dr. Hilton Y. Lam, Institute of Health Policy andDevelopment Studies, NIH2. Dr. Leonardo R. Estacio, Jr., College of Arts andSciences, UP Manila3. Dr. Ma. Esmeralda C. Silva, College of Public Health,UP Manila4. Dr. Michael Antonio F. Mendoza, College of Dentistry,UP Manila5. Dr. Ma. Susan T. Yanga-Mabunga, Department ofHealth Policy & Administration, UP Manila6. Dr. Danilo L. Magtanong, College of Dentistry, UPManila7. Dr. Alvin Munoz Laxamana, Philippine DentalAssociation8. Dr. Fina Lopez, Philippine Pediatric Dental Society, Inc9. Dr. Artemio Licos, Jr.,Department of Health NationalAssociation of Dentists10. Dr. Maria Jona D. Godoy, Professional RegulationCommission11. Ms. Anna Liza De Leon, Philippine Health InsuranceCorporation12. Ms. Nicole Sigmuend, GIZ Fit for School13. Ms. Lita Orbillo, Disease Prevention and Control Bureau14. Mr. Raymond Oxcena Akap sa Bata Philippines15. Dr. Jessica Rebueno-Santos, Department of CommunityDentistry, UP Manila16. Ms. Maria Olivine M. Contreras, Bureau of LocalGovernment Supervision, DILG17. Ms. Janel Christine Mendoza, Philippine DentalStudents Association18. Mr. Eric Raymund Yu, UP College of DentistryStudent Council19. Dr. Joy Memorando, Philippine Pediatric Society20. Dr. Sharon Alvarez, Philippine Association of DentalColleges

Introduction: Diabetes has been linked with poor clinical prognosis of hospitalized COVID-19 patients. In this nationwide database retrospective study we evaluated diabetes as a risk factor of in-hospital death. Methods: We analysed data from discharge reports from 2020 of hospitalized COVID-19 patients sent to the Polish National Health Fund. To assess the risk of in-hospital death attributed to diabetes, several multivariate logistic regression models were used. In each model in-hospital death was estimated with explanatory variables, including diabetes. Models were built either on the whole cohorts or cohorts matched with propensity score matching (PSM). They examined either main effects or included interaction of diabetes with other variables. Results: We included 174,621 patients with COVID-19 infection hospitalized in Poland in 2020. There were 40,168 diabetic patients (DPs), proportion higher than in the general population (23.0% vs. 9.5%, p&lt;0.001). Overall, 17,438 in-hospital deaths were recorded, the mortality was higher in DPs vs. nondiabetics (16.3% vs. 8.1%, p&lt;0.001). Multivariate logistic regressions showed that diabetes was an independent risk factor of death, regardless of sex and age. In the main effect analysis, odds of in-hospital death were higher by 28.3% for DPs than for nondiabetic patients. Similarly, PSM analysis including 101,578 patients, of whom 19,050 had diabetes, showed that the risk of death was higher in DPs regardless of sex and age. Odds of in-hospital death were higher by 34.9% for DPs. The impact of diabetes on COVD-19 in-hospital death differed among age groups and was the highest for patients aged 60-69. Conclusions: This nationwide study confirmed that diabetes was an independent risk of in-hospital death in the course of COVID-19. However, the relative risk attributed to diabetes might be lower than reported earlier from most of other populations and differ significantly across the age groups. Disclosure M. Kania: None. B. Kon: None. K.M. Kaminski: Other Relationship; Roche Pharmaceuticals. J. Hohendorff: Speaker's Bureau; Abbott, Novo Nordisk, Ascensia Diabetes Care, Dexcom, Inc., Bayer Inc. T. Klupa: Speaker's Bureau; Medtronic. Advisory Panel; Abbott Diabetes. Speaker's Bureau; Abbott Diabetes. Advisory Panel; Ascensia Diabetes Care. Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. Advisory Panel; Sanofi, BIOTON S.A. Speaker's Bureau; Boehringer Ingelheim Inc., Servier Laboratories. P.W. Witek: Other Relationship; Abbott Diabetes, Ascensia Diabetes Care, Medtronic, Novo Nordisk, Sanofi-Aventis Deutschland GmbH, Boehringer-Ingelheim, Roche Diabetes Care, BIOTON S.A., KRKA. M. Malecki: Advisory Panel; Abbott Diabetes. Speaker's Bureau; AstraZeneca, AlfaSigma. Advisory Panel; Novo Nordisk, Lilly, Sanofi. Speaker's Bureau; Merck & Co., Inc. Research Support; Medtronic. Advisory Panel; Dexcom, Inc. Speaker's Bureau; BIOTON S.A., Servier Laboratories, KRKA. Advisory Panel; Bayer Inc. Funding National Centre for Research and Development CRACoV-HHS project (SZPITALE-JEDNOIMIENNE/18/2020)

The recently published1, multi-site, FLASH-UK, randomized controlled trial (n=156, males 56%, Baseline HbA1c 71±9 mmol/mol, age 44±15) showed improved HbA1c and sensor-based metrics in adults with type 1 DM and an HbA1c ≥58 mmol/mol. Here we present results from pre-specified subgroup analysis for HbA1c (Table 1) and “Time in range (TIR)” (Table 2). The effect of isCGM on both HbA1c and TIR did not differ significantly across subgroups for baseline HbA1c category, treatment modality, prior structured education, sex, deprivation status or depression category. The effect of isCGM on HbA1c was larger for younger people. Those with at least a bachelor’s degree had greater TIR improvement. Conclusion: isCGM is effective across a range of clinical and demographic factors. 1N Engl J Med. 2022 Oct 20;387(16):1477-1487 Disclosure L.Leelarathna: Advisory Panel; Abbott Diabetes, Medtronic, Insulet Corporation, Sanofi, Research Support; Abbott Diabetes, Novo Nordisk, Speaker's Bureau; Sanofi, Abbott Diabetes. V.P.Taxiarchi: None. M.Burns: None. M.E.Camm: None. H.Thabit: Advisory Panel; Dexcom, Inc., Roche Diabetes Care, Research Support; Dexcom, Inc., Speaker's Bureau; Eli Lilly and Company. E.G.Wilmot: Advisory Panel; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Roche Diabetes Care, Embecta, Consultant; Springer Healthcare, Research Support; Abbott Diabetes, Diabetes UK, Insulet Corporation, Novo Nordisk, NIH - National Institutes of Health, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Ypsomed AG, Glooko, Inc. On behalf of the flash-uk trial study group: n/a. C.J.Sutton: None. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. S.Neupane: Advisory Panel; Quin, Abbott Diabetes, Roche Diabetes Care, Insulet Corporation, Other Relationship; Abbott Diabetes. G.Rayman: Other Relationship; Diabetes UK, Novo Nordisk, Research Support; Abbott Diabetes, Speaker's Bureau; Abbott Diabetes, Lilly Diabetes, Sanofi. S.Lumley: None. I.C.Cranston: Research Support; Eli Lilly and Company, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, Viatris Inc. P.Narendran: Advisory Panel; Omnipod, Speaker's Bureau; Abbott Diabetes, Lilly Diabetes. K.Barnard: Advisory Panel; Abbott Diabetes, Roche Diabetes Care, Sanofi, Consultant; LifeScan Diabetes Institute, Tandem Diabetes Care, Inc., Research Support; Novo Nordisk. Funding Diabetes UK (18/0005836)

Objective: The present study assessed impact of the MiniMed™ 780G (MM780G) advanced hybrid closed-loop (AHCL) system on glycemic metrics and safety when used with the disposable all-in-one Simplera Sync™ sensor*. Methods: Youths (aged 7-17yrs) and adults (aged 18-80yrs) with T1D were enrolled in a single-arm study (24 U.S. sites) with a ~2-week run-in where HCL (Auto Basal only) or open-loop delivery was used. This was followed by a three-month study period with AHCL activated. Glycemic outcomes and insulin delivered during the last 6-7 weeks of the study, in which system settings were optimized at investigator’s discretion, were compared to those of the run-in. Impact of recommended optimal settings (ROS, 100 mg/dL glucose target [GT] with a 2hr active insulin time [AIT]), was explored. Results: All groups showed significantly increased TIR and TITR and significantly reduced TAR, compared to run-in (Table). Use of ROS further improved TIR, TITR and TAR, in part, due to &gt;60% automated basal and bolus delivery. No episodes of device-related severe hypoglycemia or DKA occurred. Conclusion: Use of the MM780G with the Simplera Sync™ sensor was safe and demonstrated improved glycemic outcomes, compared with run-in, and compared to glycemic outcomes of the pivotal trials1,2. Similarly, a lower GT and shorter AIT were associated with a further increased TIR and reduced TAR and, here, an increased TITR. Disclosure G.P. Forlenza: Research Support; Abbott, Dexcom, Inc. Consultant; Dexcom, Inc. Research Support; Insulet Corporation. Consultant; Insulet Corporation. Research Support; Medtronic. Advisory Panel; Medtronic. Research Support; Tandem Diabetes Care, Inc. Consultant; Tandem Diabetes Care, Inc. S.A. MacLeish: Speaker's Bureau; Insulet Corporation. Advisory Panel; Prevention Bio. D.I. Shulman: Advisory Panel; Medtronic. Research Support; Medtronic. S. Accacha: Speaker's Bureau; Azurity. S.K. Garg: Research Support; Eli Lilly and Company. Advisory Panel; Medtronic. Research Support; Medtronic. Advisory Panel; Novo Nordisk. Research Support; DarioHealth Corp., Dexcom, Inc., Diasome. Advisory Panel; Roche Diabetes Care. A.L. Carlson: Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc., Eli Lilly and Company, Sanofi. Other Relationship; Novo Nordisk. Advisory Panel; MannKind Corporation. Research Support; Dexcom, Inc. K.N. Castorino: Research Support; Abbott, Dexcom, Inc. Speaker's Bureau; Dexcom, Inc. Research Support; Lilly Diabetes, Medtronic, MannKind Corporation, Insulet Corporation. Consultant; Medscape. B.E. Marks: Research Support; Tandem Diabetes Care, Inc., Dexcom, Inc., Medtronic, Digostics. Advisory Panel; International Society for Pediatric and Adolescent Diabetes, American Diabetes Association, T1D Exchange. Board Member; Juvenile Diabetes Research Foundation (JDRF). R. Lal: Consultant; Abbott, Adaptyx Biosciences, Biolinq, Capillary Biomedical, Inc., Deep Valley Labs, Gluroo, PhysioLogic Devices, Portal Insulin, Tidepool. Advisory Panel; Lilly Diabetes. C. Pihoker: None. J. Thrasher: Advisory Panel; Medtronic. Board Member; Medtronic. Research Support; Medtronic. Speaker's Bureau; Medtronic. Research Support; Eli Lilly and Company, Novo Nordisk. Speaker's Bureau; Bayer Inc. L.M. Laffel: Consultant; Dexcom, Inc. Advisory Panel; Medscape, Medtronic, Vertex Pharmaceuticals Incorporated. Consultant; Novo Nordisk. Advisory Panel; Lilly Diabetes, Provention Bio, Inc., Sanofi-Aventis U.S., Janssen Pharmaceuticals, Inc., MannKind Corporation. B. Sunil: None. B.W. Bode: Research Support; Omnipod. Speaker's Bureau; Omnipod. Research Support; Medtronic. Advisory Panel; Medtronic. J.L. Sherr: Consultant; Medtronic. Advisory Panel; Medtronic, Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Vertex Pharmaceuticals Incorporated, MannKind Corporation, StartUp Health T1D Moonshot, Bigfoot Biomedical, Inc., Cecelia Health. Speaker's Bureau; Zealand Pharma A/S. L. Ekhlaspour: Advisory Panel; Medtronic. Consultant; Medtronic, Tandem Diabetes Care, Inc. Advisory Panel; Tandem Diabetes Care, Inc. Research Support; Medtronic, MannKind Corporation. Advisory Panel; Sequel. Other Relationship; National Institutes of Health. Research Support; Juvenile Diabetes Research Foundation (JDRF). Speaker's Bureau; Insulet Corporation. J.H. Reed: None. M. Abuzzahab: Research Support; Ascendis Pharma A/S. Consultant; Ascendis Pharma A/S. Research Support; Medtronic, MannKind Corporation, Rhythm Pharmaceuticals, Inc. Consultant; Rhythm Pharmaceuticals, Inc. Research Support; Novo Nordisk. M. Church: None. Z. Dai: Employee; Medtronic. H. Ma: None. J. Solomon: None. Y. Treminio: Employee; Medtronic. J. Shin: None. A.S. Rhinehart: Employee; Medtronic. Stock/Shareholder; Medtronic. J. McVean: Employee; Medtronic. R.A. Vigersky: Employee; Medtronic.

Introduction & Objective: While the prevalence of young-onset type 2 diabetes (T2DM) is well described, population-based incidence data are scarce. We estimated secular trends (2000-2020) in diabetes incidence with an onset age at 15-39 years. Methods: We used aggregated data from registries, national health insurance schemes, or other administrative sources in eight high-income countries or jurisdictions. We used clinical diagnosis and ICD codes, and separated diabetes type based on time to insulin, continuous insulin use, and age of diabetes onset. Poisson regression models included age and calendar time with spline effects, stratified by sex and diabetes type. Results: There were 0.35 million incident diabetes cases for 0.35 billion person-years of follow-up. The figure shows stable type 1 diabetes (T1DM) incidence in Denmark, Hungary, and Japan and increasing incidence in Australia, Finland, Scotland, South Korea, and Spain (Catalonia) (estimated annual change (EAC) of 0.5% to 6.1%). Incidence of T2DM increased in 50% of jurisdictions (EAC of 2.6% to 8.5%), with higher magnitude in Asian (4.8% in South Korea and 8.5% in Japan) than in non-Asian jurisdictions (2.6% in Denmark and 3.4% in Finland). T2DM incidence was stable in Australia and Hungary and decreased in Scotland and Spain (Catalonia). Conclusion: Incidence of clinically diagnosed young-onset T2DM increased in some high-income countries but not universally. Disclosure D.J. Magliano: None. L. Chen: None. J.I. Morton: None. A. Salim: None. B. Carstensen: Stock/Shareholder; Novo Nordisk. E.W. Gregg: None. M.E. Pavkov: None. M. Arffman: Research Support; Roche Pharmaceuticals. H.M. Colhoun: Stock/Shareholder; Bayer Inc., Roche Pharmaceuticals. Research Support; Juvenile Diabetes Research Foundation (JDRF), IQVIA Inc., Diabetes UK, European Union. Advisory Panel; Novo Nordisk, Bayer Inc. K. Ha: None. T. Imamura: None. G. Jermendy: None. D. Kim: None. Z. Kiss: Employee; Merck & Co., Inc. D. Mauricio: Speaker's Bureau; Abbott, Amgen Inc., Gilead Sciences, Inc., Lilly Diabetes. Advisory Panel; Sanofi. Speaker's Bureau; Novo Nordisk. Advisory Panel; Novo Nordisk. S.J. McGurnaghan: None. Y. Nishioka: Speaker's Bureau; Sanofi, Daiichi Sankyo. S. Wild: Other Relationship; Novo Nordisk, Novo Nordisk Foundation. K. Winell: None. J.E. Shaw: Advisory Panel; GlaxoSmithKline plc. Research Support; AstraZeneca. Advisory Panel; AstraZeneca. Speaker's Bureau; AstraZeneca, Roche Diabetes Care, Boehringer-Ingelheim, Zuellig Pharma Holdings Pte. Ltd. Advisory Panel; Novo Nordisk. Speaker's Bureau; Roche Diagnostics. Advisory Panel; Roche Diagnostics, Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Abbott, Mylan. Speaker's Bureau; Sanofi. Funding Centers for Disease Control and Prevention, United States

Introduction & Objective: Hospitalization may serve as an opportune time to address uncontrolled type 2 diabetes (T2D) in elderly patients. Our objective was to examine hospitalist and primary care provider (PCP) experience caring for patients &gt; age 65 with T2D during or after hospitalization. Methods: Utilizing the electronic medical record, we identified patients age &gt;65 with T2D and A1c&gt; 8%, with hospital discharge November 2022-April 2023 and identified the hospitalists and PCPs caring for these patients. Sixteen semi-structured interviews were conducted with providers within 90 days of patient discharge. Interviews were audio recorded, transcribed, and transcripts were thematically analyzed using an inductive approach. Results: Hospitalists and PCPs both viewed hospitalization as an opportunity to make therapeutic changes for patients with uncontrolled T2D. A hospitalist described “an opportunity to ‘reassess’ medications previously set "on cruise control." Providers use blood sugar and A1c to inform decisions, but reported variation in data prompting medication change. Hospitalists expressed trepidation around “making drastic changes,” or one stating “⋯ I might tweak things a little bit and say⋯ ‘follow up with your PCP,” while PCPs draw upon their relationships with patients and see “the outpatient setting [as] where the care of diabetic patients takes place most of the time.” Yet PCPs may appreciate when changes are made in the hospital, one stating "It’s psychologically a little easier, if they’ve already started [medicines prescribed by hospitalists]." Conclusion: PCPs and hospitalists both appreciate hospitalization as an opportune time to make T2D therapeutic changes but therapeutic inertia was identified among both provider types. Efforts to improve hospitalist-PCP communication about diabetes treatment as well as standardized protocols for treatment adjustment should be explored for older patients with uncontrolled T2D at the time of discharge. Disclosure V. Chepp: None. S.P. Masiano: None. A. Milinovich: Research Support; Novo Nordisk, Bayer Inc., Merck & Co., Inc., Twin Health, National Institutes of Health, Eli Lilly and Company, Pfizer Inc. J. Fox: None. K.M. Pantalone: Speaker's Bureau; AstraZeneca. Consultant; AstraZeneca. Board Member; Bayer Inc. Research Support; Bayer Inc. Speaker's Bureau; Corcept Therapeutics. Consultant; Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc. Speaker's Bureau; Merck & Co., Inc. Research Support; Merck & Co., Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Twin Health. Consultant; Sanofi. A.D. Misra-Hebert: Research Support; Bayer Inc., Merck & Co., Inc., Novo Nordisk.

The study investigated the effects of the level of global and local attacks against ships on economic development in Nigeria. It also examined the effects of volume of cargo pilfered in Nigeria ports as a result of insecurity on the economic growth in Nigeria. The study employed secondary data sourced from from the Nigerian ports authority, the National bureau for statistics (NBS) and the International Maritime Bureau (IMB) on the Gross Domestic Product (GDP), levels of pirate attacks against ships in local and global waters, and volume of cargo pilferages in ports. The multiple regression analysis method was used to analyze the dataset obtained using GDP as the dependent variable while global attacks, local attacks and volume of cargo pilfered were used as independent variables. It was found that the effect of maritime piracy and sea robbery on economic growth and development is expressed by the equation: GDPt = 1638944 + 5745.61GLOTAKSt – 34587.7LOTAKSt + 193.25VOCARPt. This implies that economic growth in Nigeria increase with increase in attacks against ships in global waters, it decreases with increase in attacks against ships in Nigerian maritime domain and increases with increase in volume of cargo pilfered from the ports. A unit increase in level of global attacks increases the GDP by 5745.61 units while a unit increase in local attacks against ships trading in Nigerian waters decreases the Gross Domestic Product (GDP) by 34587.7 units. Similarly, a unit increase in volume of cargo pilfered from the ports increase the GDP by 193.25 units. It concluded that maritime piracy and sea robbery attacks against ships have significant impact on economic growth and development in Nigeria.

Background: Safety and effectiveness outcomes of individuals using the MiniMed™ 780G system with the no-calibration Guardian™ 4 sensor during the first three months of use were analyzed. Methods: Participants (N=176, aged 7-75 years) with T1D used the Conformitè Europëenne-marked MiniMed™ 780G system. Safety and effectiveness endpoints (mean A1C, sensor glucose [SG], percentage of time spent at SG ranges and glucose variability) were collected over three months and summarized. Endpoints were also assessed when recommended settings (target of 100mg/dL and active insulin time of 2-3 hours) were used. Results: There was no DKA or severe hypoglycemia. At 3 months, A1C was 7.1% (N=164) , 7.2% (N=101) and 6.8% (N=63) for overall, pediatric and adult participants, respectively. Additional glycemic metrics are shown (Table) . With recommended settings, time spent in target range (TIR, 70-180 mg/dL) was 74.7% (N=119) , 72.7% (N=65) and 77.0% (N=54) , respectively, and time spent below range (TBR&lt;70mg/dL) was 2.1%, 2.4% and 1.7%, respectively. Conclusion: This analysis demonstrates that individuals safely exceeded international consensus-recommended TIR and TBR goals when using the MiniMed™ 780G system with the Guardian™ 4 sensor. These results mirror those of the pivotal trial during use of the calibration-requiring Guardian™ sensor 3. Disclosure R. A. Vigersky: Employee; Medtronic. C. Pihoker: None. R. Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. J. Reed: None. J. Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker’s Bureau; Lilly Diabetes. D. I. Shulman: Advisory Panel; Medtronic. R. H. Slover: None. J. Thrasher: Advisory Panel; Eli Lilly and Company, Medtronic, Board Member; Medtronic, Consultant; Eli Lilly and Company, Medtronic, Research Support; Eli Lilly and Company, Medtronic, Novo Nordisk, Speaker’s Bureau; Bayer AG, Eli Lilly and Company, Medtronic, Sanofi. X. Chen: Employee; Medtronic, Medtronic. M. Liu: None. T. L. Cordero: Employee; Medtronic, Medtronic. B. W. Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker’s Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. M. Vella: Employee; Medtronic. A. S. Rhinehart: Employee; Medtronic, Stock/Shareholder; Medtronic. J. Shin: Employee; Medtronic. R. L. Brazg: Research Support; Abbott Diabetes, Lilly Diabetes, Medtronic, Novo Nordisk, Roche Diagnostics, Senseonics. B. A. Buckingham: Advisory Panel; Arecor, Lilly Diabetes, Medtronic, Other Relationship; Insulet Corporation, Research Support; Insulet Corporation, Lilly Diabetes, Medtronic. A. L. Carlson: Advisory Panel; MannKind Corporation, Employee; Bright Health Group, Other Relationship; Medtronic, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, UnitedHealth Group. K. B. Kaiserman: Advisory Panel; Medtronic, Consultant; Medtronic, Employee; MannKind Corporation, Research Support; Medtronic, Speaker’s Bureau; Medtronic, Stock/Shareholder; MannKind Corporation. M. Kipnes: None. D. R. Liljenquist: None. A. Philis-tsimikas: Advisory Panel; Bayer AG, Novo Nordisk, Research Support; Lilly Diabetes, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Viking Therapeutics.

Background and Aims: IsCGM is increasingly used by people with type 1 diabetes. The impact on psychosocial outcomes and experiences reported by intervention participants relative to controls were assessed in a sub-study of the UK multi-centre RCT (n=156, Females 44%, Baseline HbA1c 71±9 mmol/mol, age 44±15) to determine impact on participants’ lived experiences. Methods: mixed-methods sub-study including validated questionnaires (all) and free-text questions (intervention only) exploring diabetes-related distress, device and treatment satisfaction and user experience. Questionnaires were administered at baseline and again at 24 weeks. HCPs also completed questionnaires post-study. Results: isCGM participants reported significantly lower feelings of powerlessness (p=0.045) and management distress (p&lt;0.001) in the Type 1 diabetes distress score than the control participants. There were no significant differences in depression (PHQ-9) or eating disorders measures, but diabetes treatment satisfaction (p&lt;0.001) and glucose monitoring satisfaction (p&lt;0.001) were greater for isCGM participants. Free-text data shows improved quality of life reported by n=33 isCGM participants including better diabetes control, improved control overnight, reduced anxiety and greater understanding of glucose trends and data. Reported downsides were cited by n=39 isCGM participants and included lack of accuracy, poor connectivity and sensor irritation. All participants would continue to use the device if given the choice. HCPs (n=24) reported improved communication and information sharing with participants, with easy access to the data. Their most commonly cited benefit was improved HbA1c. Conclusion: moderate improvements in psychosocial outcomes on validated measures were reported by intervention participants using isCGM. Challenges with technology persist, although these did not dampen enthusiasm by participants for continued use. Disclosure K.Barnard: Advisory Panel; Abbott Diabetes, Roche Diabetes Care, Sanofi, Consultant; LifeScan Diabetes Institute, Tandem Diabetes Care, Inc., Research Support; Novo Nordisk. M.Burns: None. H.Thabit: Advisory Panel; Dexcom, Inc., Roche Diabetes Care, Research Support; Dexcom, Inc., Speaker's Bureau; Eli Lilly and Company. E.G.Wilmot: Advisory Panel; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Roche Diabetes Care, Embecta, Consultant; Springer Healthcare, Research Support; Abbott Diabetes, Diabetes UK, Insulet Corporation, Novo Nordisk, NIH - National Institutes of Health, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, Ypsomed AG, Glooko, Inc. L.Leelarathna: Advisory Panel; Abbott Diabetes, Medtronic, Insulet Corporation, Sanofi, Research Support; Abbott Diabetes, Novo Nordisk, Speaker's Bureau; Sanofi, Abbott Diabetes. V.P.Taxiarchi: None. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. S.Neupane: Advisory Panel; Quin, Abbott Diabetes, Roche Diabetes Care, Insulet Corporation, Other Relationship; Abbott Diabetes. G.Rayman: Other Relationship; Diabetes UK, Novo Nordisk, Research Support; Abbott Diabetes, Speaker's Bureau; Abbott Diabetes, Lilly Diabetes, Sanofi. S.Lumley: None. I.C.Cranston: Research Support; Eli Lilly and Company, Speaker's Bureau; Abbott Diabetes, AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, Viatris Inc. P.Narendran: Advisory Panel; Omnipod, Speaker's Bureau; Abbott Diabetes, Lilly Diabetes. C.J.Sutton: None. Funding Diabetes UK (18/0005836)

Introduction: We aimed to study the association of T1D polygenic score (PS) & C-peptide (C-pep) with the risk of DKA in DECLARE-TIMI 58. Methods: DECLARE-TIMI 58 was a CV outcomes trial of dapagliflozin (DAPA) vs. placebo (PBO) in pts clinically diagnosed with T2D. T1D PS consists of scores based on HLA and non-HLA allele composition. High T1D PS was defined as having both HLA and non-HLA PS within the top tertile. Fasting C-pep &lt;0.4 nmol/L was considered low. Pts were divided into 4 groups based on the presence/absence of high T1D PS and low C-pep. Results: Among 10,956 pts with genetic data, 27 (2.5%; 21 in DAPA and 6 in PBO) had DKA over 4.2 yrs. Of all pts, 1,272 (11.6%) had high T1D PS and their risk of DKA was 4-fold higher vs the rest (HR 3.90, 95% CI 1.75-8.70). 9.3% of all pts had low C-pep, and 1.6% had both high T1D PS and low C-pep. The 4-yr KM rate for DKA in pts with no risk factors was 0.06%, followed by 0.21% in pts with high T1D PS only, 1.38% in pts with low C-pep only, and 4.28% in pts with both (Fig A). Absolute differences in rates between DAPA and PBO tended to be greater in the higher-risk groups (P-trend &lt;0.001: Fig B). Conclusion: Although rare overall, DKA was more common in DAPA arm, and it was largely confined to high-risk pts defined by T1D PS and C-peptide. These tools can help identify pts at increased risk of DKA associated with SGTL2i. The clinical implications of these findings require further investigation. Disclosure Y. Kang: None. A. Cahn: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Bayer Inc. Advisory Panel; Eli Lilly and Company. I. Raz: Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Johnson & Johnson Medical Devices Companies, Bayer Inc. F. Moura: Consultant; Janssen Pharmaceuticals, Inc. D.L. Bhatt: Advisory Panel; Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed,. Board Member; American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);. Consultant; Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene. Other Relationship; Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute, Boston Scientific, Cleveland Clinic, Contego Medical, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai, Novartis, Popul, ACC, Arnold and Porter Law Firm, Baim Institute, Belvoir Publications, CSL Behring, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the ACC, K2P, Level Ex, Medtelligence/Re, Population Health Research Institute, Wiley, Clinical Cardiology, Lexicon Pharmaceuticals, Inc. Research Support; Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scienti, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Mode, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio. Other Relationship; Elsevier (Editor, Braunwald’s Heart Disease), Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions, American College of Cardiology, FlowCo. Stock/Shareholder; Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock). S.E. Inzucchi: Consultant; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc., Pfizer Inc., Novo Nordisk, Bayer Inc. L.A. Leiter: Advisory Panel; Abbott. Other Relationship; Amarin Corporation, Amgen Inc., Applied Therapeutics Inc. Advisory Panel; AstraZeneca. Other Relationship; Bayer Inc. Advisory Panel; Boehringer-Ingelheim. Other Relationship; CRISPR Therapeutics Other, Eli Lilly and Company. Speaker's Bureau; EOCI Pharmacomm. Research Support; ESPERION Therapeutics, Inc. Other Relationship; HLS Therapeutics Inc. Research Support; Kowa Company, Ltd., Lexicon Pharmaceuticals, Inc. Advisory Panel; Merck & Co., Inc. Speaker's Bureau; Novartis AG. Advisory Panel; Novo Nordisk. Other Relationship; Novo Nordisk Canada Inc. Speaker's Bureau; Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Toronto Knowledge Translation Working Group. Other Relationship; Up-To-Date. D.K. McGuire: Other Relationship; Merck & Co., Inc., Eli Lilly and Company, Boehringer-Ingelheim, Novo Nordisk, Pfizer Inc., AstraZeneca. Consultant; Bayer Inc., Lexicon Pharmaceuticals, Inc., Altimmune Inc., Intercept Pharmaceuticals, Inc., Applied Therapeutics. J. Wilding: Speaker's Bureau; Boehringer-Ingelheim. Consultant; Eli Lilly and Company, Napp Pharmaceuticals Limited, Novo Nordisk. Advisory Panel; AstraZeneca. Consultant; Alnylam Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc. Speaker's Bureau; Sanofi. Consultant; A. Menarini Diagnostics. I.A. Gause-Nilsson: Employee; AstraZeneca. J. Oscarsson: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca. N. Marston: Research Support; Ionis Pharmaceuticals, Amgen Inc., Pfizer Inc. C.T. Ruff: Research Support; Anthos, AstraZeneca, Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Novartis AG. Other Relationship; Altimmune Inc. Advisory Panel; Bayer Inc., Merck & Co., Inc., Anthos, Janssen Pharmaceuticals, Inc. M.S. Sabatine: Research Support; Abbott, Amgen Inc. Consultant; Amgen Inc. Research Support; Anthos. Consultant; Anthos. Research Support; AstraZeneca. Consultant; AstraZeneca, Beren Therapeutics. Research Support; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Research Support; Daiichi Sankyo. Consultant; Dr. Reddy's Laboratories. Research Support; Ionis Pharmaceuticals, Merck & Co., Inc. Consultant; Merck & Co., Inc., Moderna, Inc. Research Support; Novartis AG. Consultant; Novo Nordisk. Research Support; Pfizer Inc. Consultant; Precision Biosciences. Research Support; Saghmos Therapeutics. Consultant; Silence Therapeutics. Research Support; Verve Therapeutics. S.D. Wiviott: Consultant; Novo Nordisk, Varian, Icon. Research Support; Amgen Inc., Merck & Co., Inc., AstraZeneca, Pfizer Inc. Other Relationship; Vertex Pharmaceuticals Incorporated, Flagship Pioneering. Funding National Institutes of Health (5T32DK007529)

Introduction: We explored findings associated with the risk of DKA in pts with T2D, with and without dapagliflozin (DAPA). Methods: DECLARE-TIMI 58 was a CV outcomes trial of 17160 pts with T2D randomized to DAPA vs placebo (PBO) with a median follow-up of 4.2 yrs. Pts with known T1D were excluded. DKA events adjudicated as definite or probable were analyzed. Results: DKA occurred in 27/8574 pts (0.31%) in DAPA vs 12/8569 (0.14%) in PBO arm (HR 2.18 [1.10-4.30]). Pts who developed DKA were more likely to be insulin users (82.1% vs 40.8%) and had a longer duration of T2D (14 vs 11 yrs), higher HbA1c (9.0% vs 8.0%), lower fasting C-peptide (C-pep; 0.2 vs 1.0 nmol/L) and HOMA2-B (20.7 vs 58.0; P&lt;0.02 for all). 63% of DKA events occurred in pts with fasting C-pep &lt;0.4 nmol/L and no DKA occurred in pts with C-pep &gt;0.97 nmol/L (Fig A). The 4-yr KM rate of DKA in pts with C-pep &lt;0.4 vs ≥0.4 nmol/L was 1.4% vs 0.09% (aHR 15.7 [7.7-32.2]). The absolute risk difference between DAPA and PBO was 1.84% vs 0.07% in pts with C-pep &lt;0.4 vs ≥0.4 nmol/L (Fig B). Conclusion: In DECLARE-TIMI 58, DKA was rare, and occurred mostly in pts with impaired insulin secretion. In pts with C-pep ≥0.4 nmol/L, the excess in DKA with DAPA was less than 1/1000pts/yr. Further research is needed to determine the utility of prospective C-peptide testing when initiating SGLT2i in pts suspected to have insulin deficiency. Disclosure Y. Kang: None. A. Cahn: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Bayer Inc. Advisory Panel; Eli Lilly and Company. I. Raz: Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Johnson & Johnson Medical Devices Companies, Bayer Inc. F. Moura: Consultant; Janssen Pharmaceuticals, Inc. D.L. Bhatt: Advisory Panel; Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed,. Board Member; American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);. Consultant; Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene. Other Relationship; Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute, Boston Scientific, Cleveland Clinic, Contego Medical, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai, Novartis, Popul, ACC, Arnold and Porter Law Firm, Baim Institute, Belvoir Publications, CSL Behring, Cowen and Company, Duke Clinical Research Institute, HMP Global, Journal of the ACC, K2P, Level Ex, Medtelligence/Re, Population Health Research Institute, Wiley, Clinical Cardiology, Lexicon Pharmaceuticals, Inc. Research Support; Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scienti, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Mode, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio. Other Relationship; Elsevier (Editor, Braunwald’s Heart Disease), Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions, American College of Cardiology, FlowCo. Stock/Shareholder; Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock). S.E. Inzucchi: Consultant; AstraZeneca, Boehringer-Ingelheim, Merck & Co., Inc., Pfizer Inc., Novo Nordisk, Bayer Inc. L.A. Leiter: Advisory Panel; Abbott. Other Relationship; Amarin Corporation, Amgen Inc., Applied Therapeutics Inc. Advisory Panel; AstraZeneca. Other Relationship; Bayer Inc. Advisory Panel; Boehringer-Ingelheim. Other Relationship; CRISPR Therapeutics Other, Eli Lilly and Company. Speaker's Bureau; EOCI Pharmacomm. Research Support; ESPERION Therapeutics, Inc. Other Relationship; HLS Therapeutics Inc. Research Support; Kowa Company, Ltd., Lexicon Pharmaceuticals, Inc. Advisory Panel; Merck & Co., Inc. Speaker's Bureau; Novartis AG. Advisory Panel; Novo Nordisk. Other Relationship; Novo Nordisk Canada Inc. Speaker's Bureau; Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Toronto Knowledge Translation Working Group. Other Relationship; Up-To-Date. D.K. McGuire: Other Relationship; Merck & Co., Inc., Eli Lilly and Company, Boehringer-Ingelheim, Novo Nordisk, Pfizer Inc., AstraZeneca. Consultant; Bayer Inc., Lexicon Pharmaceuticals, Inc., Altimmune Inc., Intercept Pharmaceuticals, Inc., Applied Therapeutics. J. Wilding: Speaker's Bureau; Boehringer-Ingelheim. Consultant; Eli Lilly and Company, Napp Pharmaceuticals Limited, Novo Nordisk. Advisory Panel; AstraZeneca. Consultant; Alnylam Pharmaceuticals, Inc., Rhythm Pharmaceuticals, Inc. Speaker's Bureau; Sanofi. Consultant; A. Menarini Diagnostics. I.A. Gause-Nilsson: Employee; AstraZeneca. J. Oscarsson: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca. N. Marston: Research Support; Ionis Pharmaceuticals, Amgen Inc., Pfizer Inc. C.T. Ruff: Research Support; Anthos, AstraZeneca, Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Novartis AG. Other Relationship; Altimmune Inc. Advisory Panel; Bayer Inc., Merck & Co., Inc., Anthos, Janssen Pharmaceuticals, Inc. M.S. Sabatine: Research Support; Abbott, Amgen Inc. Consultant; Amgen Inc. Research Support; Anthos. Consultant; Anthos. Research Support; AstraZeneca. Consultant; AstraZeneca, Beren Therapeutics. Research Support; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Research Support; Daiichi Sankyo. Consultant; Dr. Reddy's Laboratories. Research Support; Ionis Pharmaceuticals, Merck & Co., Inc. Consultant; Merck & Co., Inc., Moderna, Inc. Research Support; Novartis AG. Consultant; Novo Nordisk. Research Support; Pfizer Inc. Consultant; Precision Biosciences. Research Support; Saghmos Therapeutics. Consultant; Silence Therapeutics. Research Support; Verve Therapeutics. S.D. Wiviott: Consultant; Novo Nordisk, Varian, Icon. Research Support; Amgen Inc., Merck & Co., Inc., AstraZeneca, Pfizer Inc. Other Relationship; Vertex Pharmaceuticals Incorporated, Flagship Pioneering. Funding National Institutes of Health (5T32DK007529)

The Virtual Diabetes Specialty Clinic (VDiSC) provided type 1 (T1D) and type 2 diabetes (T2D) adults taking insulin virtual care with remote CGM training and support. HbA1c improved from baseline to 6 months in T1D (7.8% to 7.0%) and T2D (8.2% to 7.0%) with increased time in range (70-180 mg/dL; TIR). Here we compare glycemic outcomes (Table 1) and duration of remote CGM training visits (Table 2) in adults ages &lt;40 yr, 40-59 yr and ≥ 60 yr. HbA1c and %TIR improved in each group. Limitations include a small sample size that was mostly White. Results suggest that both T1D and T2D adults ≥60 years of age experience glycemic benefit after remote training and support in the use of CGM from CDCESs, but when compared to young adults, older adults require more time for training. Support for approaches that address the individual needs of older adults with diabetes is required. Disclosure R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. T.S.Mcarthur: None. B.A.Olson: Stock/Shareholder; Abbott. S.Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T.Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. D.Raghinaru: None. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. Z.Thompson: None. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. T.L.Cushman: None. R.L.Gal: None. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. D.F.Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. K.K.Hood: Consultant; Cecelia Health. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. Funding The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.

Introduction & Objective: The hospitalization period may be an opportunity for providers to initiate treatment changes for patients with uncontrolled T2D. We examined factors associated with medication changes and improved A1c levels among older adults with T2D after hospitalization. Methods: This retrospective cohort study utilized electronic medical records of patients ≥65 years old with T2D and A1c ≥8% discharged to home from 11 Cleveland Clinic Health System hospitals from 11/2022-04/2023. Medication change was defined as a change in medication regimen or daily dosage post-hospitalization. Improved A1c level was defined as A1c &lt;8% at 180 days post-discharge in a subsample of patients with medication change and for whom the change preceded A1c testing. Predictors of medication change and A1c &lt;8% post-hospitalization were modeled using logistic regressions. Results: The cohort included 359 patients, mean (SD) age 74 (±7) y, 61% White, 95% non-Hispanic, 51% female, 48% married, and 85% had Medicare. All patients were followed for six months. Treatment changes occurred in 65% of patients within 30 days and 82% within 90 days from discharge, with mean days to treatment change as 31 (95%CI: 26, 35). Patients with higher A1c values pre-hospitalization, A1c tests during hospitalization, and higher readmission risk were more likely to have medication changes. A1c data was available in N=289 (81%) patients at 6 months. The proportion achieving A1c &lt;8% at 180 days was 42% (121/289) but significantly higher among those who had treatment change within 30 days (51% vs. 14%, p=0.003; OR=3.22, 95%CI: 1.01,10.21). Lower A1c value pre-hospitalization and A1c testing during hospitalization were also associated with A1c &lt;8%. Conclusion: A1c testing during hospitalization was an important predictor for treatment change and improved A1c levels in older patients with T2D with A1c &lt;u&gt;&gt;&lt;/u&gt;8%. Recognition of the hospitalization period as an opportunity to address high A1c levels is thus crucial. Disclosure S.P. Masiano: None. L.G. Tereshchenko: None. V. Chepp: None. A. Milinovich: Research Support; Novo Nordisk, Bayer Inc., Merck & Co., Inc., Twin Health, National Institutes of Health, Eli Lilly and Company, Pfizer Inc. J. Fox: None. K.M. Pantalone: Speaker's Bureau; AstraZeneca. Consultant; AstraZeneca. Board Member; Bayer Inc. Research Support; Bayer Inc. Speaker's Bureau; Corcept Therapeutics. Consultant; Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc. Speaker's Bureau; Merck & Co., Inc. Research Support; Merck & Co., Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Twin Health. Consultant; Sanofi. A.D. Misra-Hebert: Research Support; Bayer Inc., Merck & Co., Inc., Novo Nordisk. Funding This work was internally supported with funding from the Healthcare Delivery and Implementation Science Center at Cleveland Clinic.

Introduction and Objective: Several GLP-1 drugs are FDA approved for type 2 diabetes (T2D) or obesity. The 2024 ADA standards of care highlight that for individuals with T2D and obesity/overweight, GLP-1 therapy is preferred. While many adults with T1D are overweight/obese, GLP-1 use in this population is not well characterized. Data from the T1D Exchange Online Registry was leveraged to assess self-reported GLP-1 use by demographic and clinical characteristics. Methods: Registry participants complete questionnaires annually. This analysis includes T1D adults who completed a questionnaire in 2023. Results: Among 8,053 adults, 470 (5.8%) reported using a GLP-1, % using GLP-1 by characteristics are shown in the Table. Median HbA1c was similar in those using (6.6%) and not using (6.5%) GLP-1. GLP-1 use was more common in adults with obesity and cardiovascular disease and less common among those with severe hypoglycemia. Among those with known GLP-1 type (n=109), 67% used semaglutide, 16% tirzepatide, 10% dulaglutide, 6% liraglutide and 1% exenatide. Conclusion: GLP-1 use in this cohort of adults with T1D is low despite increasing prevalence of obesity. With increased focus on treatment of obesity, trends of GLP-1 use in those with T1D may change over time. Considering the benefits of these agents, further prospective research focused on this population is needed. Disclosure K. Miller: Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. H. Nguyen: None. J.L. Sherr: Consultant; Medtronic. Advisory Panel; Medtronic, Insulet Corporation. Speaker's Bureau; Insulet Corporation. Advisory Panel; Vertex Pharmaceuticals Incorporated, MannKind Corporation, StartUp Health T1D Moonshot, Bigfoot Biomedical, Inc., Cecelia Health. Speaker's Bureau; Zealand Pharma A/S. Y.C. Kudva: Research Support; Dexcom, Inc. Other Relationship; Tandem Diabetes Care, Inc., Medtronic. A.L. Carlson: Research Support; Medtronic, Insulet Corporation, Tandem Diabetes Care, Inc., Eli Lilly and Company, Sanofi. Other Relationship; Novo Nordisk. Advisory Panel; MannKind Corporation. Research Support; Dexcom, Inc. N. Chaytor: None. D. DeSalvo: Advisory Panel; Insulet Corporation. Consultant; Dexcom, Inc. M.E. Hilliard: None. B.E. Marks: Research Support; Tandem Diabetes Care, Inc., Dexcom, Inc., Medtronic, Digostics. Advisory Panel; International Society for Pediatric and Adolescent Diabetes, American Diabetes Association, T1D Exchange. Board Member; Juvenile Diabetes Research Foundation (JDRF). M.L. Litchman: Research Support; American Diabetes Association, Association of Diabetes Care & Education Specialists, Dexcom, Inc. Other Relationship; Association of Diabetes Care & Education Specialists. Research Support; National Institutes of Health. C. Berget: Speaker's Bureau; Dexcom, Inc., Insulet Corporation, embecta. W. Wolf: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust (G-2103-05086)

Objective: A CGM sensor that is disposable and requires no calibration may make glucose management easier for people living with diabetes. The present study reports on the interim analysis of a new disposable zero-calibration sensor in adults and youth with type 1 (T1D) or type 2 diabetes (T2D) . Methods: A prospective study enrolled individuals (N=123 adults, aged 18-80 years and N=120 youth, aged 2-17 years) with diabetes at 13 sites in the United States. Raw sensor data were compared with a YSI (Yellow Springs Instruments) or blood glucose (BG) reference and involved N=15388 paired points (pps) from the arm of adults, and N=8627pps from the arm and 7781pps from the buttock of youth. Data were processed using a new zero-calibration algorithm. The primary endpoint was agreement within 20%/20mg/dL (sensor glucose [SG] ≥80mg/dL/&lt;80mg/dL) . Multiple secondary and descriptive endpoints included agreement within 15%/15mg/dL (SG ≥70mg/dL/&lt;70mg/dL) and the mean absolute relative difference (MARD) for the adult arm location and youth arm and buttock locations. Results: The overall 20%/20mg/dL agreement rate was 90.6% for adults, and 87.8% and 88.5% for youth arm and buttock, respectively. For adults, the 15%/15mg/dL agreement rates were 90.1% and 87.6% (SG &lt;70 mg/dL and SG &gt;180 mg/dL, respectively) . For youth, the 15%/15mg/dL rates were 93.2% and 86.5% for the arm (SG &lt;70 mg/dL and SG &gt;180 mg/dL, respectively) and 90.3% and 89.5% for the buttock (SG &lt;70 mg/dL and SG&gt;180 mg/dL, respectively) . The MARDs were 10.2% for adults, and 10.7% and 10.1% for youth arm and buttock, respectively. Conclusion: These interim findings on the clinical performance of the new disposable and calibration-free sensor are good and may support non-adjunctive insulin dosing in standalone CGM and automated insulin delivery systems. Disclosure B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker’s Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. J.Shin: Employee; Medtronic. F.Peng: None. S.Huang: n/a. A.S.Rhinehart: Employee; Medtronic, Stock/Shareholder; Medtronic. R.A.Vigersky: Employee; Medtronic. T.S.Bailey: Advisory Panel; Abbott Diabetes, CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Consultant; LifeScan, Sanofi, Research Support; Abbott Diabetes, Abbott Diagnostics, Biolinq, Capillary Biomedical, Inc., Dexcom, Inc., Eli Lilly and Company, Kowa Research Institute, Inc., Livongo, MannKind Corporation, Medtronic, Novo Nordisk, REMD Biotherapeutics, Sanofi, Sanvita Medical, Senseonics, ViaCyte, Inc., vTv Therapeutics, Zealand Pharma A/S, Speaker’s Bureau; Becton, Dickinson and Company, Medtronic, Sanofi. K.N.Castorino: Consultant; Lilly Diabetes, Research Support; Abbott Diabetes, Dexcom, Inc., Drawbridge Health, Inc., Eyenuk, Inc., Laxmi Therapeutic Devices, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Speaker’s Bureau; Dexcom, Inc. M.P.Christiansen: Research Support; Abbott Diabetes, Ascensia Diabetes Care, AstraZeneca, Biolinq, Dexcom, Inc., Eli Lilly and Company, Helixmith, MannKind Corporation, Medtronic, Merck Sharp & Dohme Corp. S.K.Garg: Advisory Panel; Bayer AG, Medtronic, Zealand Pharma A/S, Consultant; Novo Nordisk, Research Support; Dexcom, Inc., Medtronic. K.B.Kaiserman: Advisory Panel; Medtronic, Consultant; Medtronic, Employee; MannKind Corporation, Research Support; Medtronic, Speaker’s Bureau; Medtronic, Stock/Shareholder; MannKind Corporation. D.R.Liljenquist: None. D.I.Shulman: Advisory Panel; Medtronic. R.H.Slover: None.

There is limited experience with continuous glucose monitoring (CGM) in intensive care units (ICUs). We assessed the effectiveness, safety, and accuracy of real-time CGM use in COVID-19 ICUs. We pooled data from three academic centers using hybrid protocols combining point of care (POC) blood glucose (BG) with non-adjunctive CGM. At hospitals A and B, CGM was used non-adjunctively with POC at least every 6 hours. At hospital C, POC BG was performed every two hours. We also examined CGM performance during lowest pAO2, oxygen saturation, pH, and mean arterial pressure. Of 169 patients, mean age was 60.9±12.2 years, and 82%, 93%, and 62% received corticosteroids, mechanical ventilation, and vasopressors respectively. Median duration of IV insulin was 118, 156, and 50 hours at hospitals A, B, and C respectively. Mean POC BG frequency was 10.2±6.1, 7.0±5.2, and 16±6.5 times/day on day 1 of IV insulin and 6.7±3.1, 6.0±3.5, and 12.2±5.8 times/day thereafter. The median percent CGM time in range (TIR, 70-180mg/dl) was 72%, 70% and 46% during IV insulin. Median time &lt;70mg/dl was &lt;0.1% for all hospitals. The absolute relative difference between CGM and POC did not correlate with hemodynamic instability, Figure. This data indicates hybrid monitoring can reduce POC frequency while safely maintaining glucose. Sensor-meter agreement was not associated with abnormal physiologic parameters and requires further study. Disclosure E.R.Faulds: Advisory Panel; Dexcom, Inc., Other Relationship; A1Control, LLC, Research Support; Dexcom, Inc., Speaker's Bureau; Dexcom, Inc., Medscape. M.Garcia: None. S.Chandra: None. F.J.Pasquel: Consultant; Dexcom, Inc., Medscape, Research Support; Dexcom, Inc., Ideal Medical Technologies. K.M.Dungan: Board Member; Elsevier, Consultant; Eli Lilly and Company, Dexcom, Inc., Other Relationship; UpToDate, Research Support; Dexcom, Inc., Abbott, ViaCyte, Inc., Sanofi, Speaker's Bureau; Academy for Continued Healthcare Learning, Cardiometabolic Health Congress, Medscape, Integritas. Y.Badakhshi: None. A.Boutsicaris: None. M.C.Exline: Other Relationship; Abbott Nutrition. J.Hester: None. L.G.Jones: None. M.Mcnett: Research Support; Dexcom, Inc., National Institutes of Health. J.D.Miller: Advisory Panel; MannKind Corporation, Employee; Medtronic, Research Support; Dexcom, Inc. R.Shah: None.

Aims: Poor glycemic control may contribute to the very high mortality rate in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) . Whether analogue compared to human insulin therapy associates with different outcomes is unknown. Methods: Incident HD patients with T2D on insulin treatment enrolled at one of the 288 Fresenius Medical Care facilities across 7 European countries between 2007-20were identified using an established administrative data algorithm. All patients were censored after 3 years of observation. Following multiple imputation, inverse probably weighting (IPW) and instrumental variable (IV; using country) analyses were used to generate Cox-proportional hazards to estimate analogue compared to human insulin hazard ratios for all-cause mortality (ACM) , MACE, hospitalization, and confirmed hypoglycemia (&lt;3.0 mmol/L during a dialysis session) . Results: About 713 analogue users were compared to 733 subjects treated with human insulin. Significant variation in prescription by country was observed. IPW hazard ratios [95% confidence intervals] for patients on analogue compared to human insulin were 0.8[0.659-0.991] for ACM (p=0.042) , 0.817 [0.679-0.983] for MACE (p=0.033) , 0.757 [0.665-0.861] for hospitalization (p&lt;0.001) , and 1.6[1.1419-2.268] for hypoglycemia (p=0.008) . Consistent strength and direction of the associations were observed in the IV analysis and across sensitivity analyses. Conclusions: In this large, multinational cohort of patients with T2D on HD, compared to human insulins, analogue insulins were associated with better clinical outcomes, although hypoglycemia rates were increased. Whether analogue insulins represent the preferred therapy in this group requires confirmatory evidence from a clinical trial. Disclosure T. Ebert: Consultant; Sanofi, Santis. Research Support; AstraZeneca, Novo Nordisk. N. Sattar: None. M. Greig: None. C. Lamina: None. K. Eckardt: Consultant; Akebia Therapeutics, Inc. Research Support; Bayer AG, Evotec International GmbH, Fresenius Medical Care. Speaker's Bureau; AstraZeneca, Bayer AG, Otsuka Pharmaceutical Co., Ltd. J. Floege: Other Relationship; Novo Nordisk A/S. F. Kronenberg: Advisory Panel; Amgen Inc., Novartis AG. P. Stenvinkel: Advisory Panel; AstraZeneca, Baxter, Fresenius Medical Care, Reata Pharmaceuticals, Inc., Vifor Pharma Management Ltd. Speaker's Bureau; Astellas Pharma Inc., Bayer AG, Novo Nordisk. D.C. Wheeler: Advisory Panel; Bayer AG, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., GlaxoSmithKline plc., Janssen Global Services, LLC, Merck Sharp & Dohme Corp., Mundipharma, Tricida, Inc., Vifor Pharma Management Ltd. Consultant; AstraZeneca. Speaker's Bureau; Amgen Inc., Astellas Pharma Inc. J. Fotheringham: Advisory Panel; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Fresenius Medical Care, Novartis Pharmaceuticals Corporation, Vifor Pharma Management Ltd. Funding Amgen (Europe) GmbH- Rotkreuz, Switzerland- Swedish Research Council (grant 2009-1068) - Swedish Heart and Lung Foundation (20160384) - Njurfonden- Westmans Foundation- Novo Nordisk (Postdoctoral fellowship program run inpartnership with Karolinska Institutet, Stockholm,Sweden) - Karolinska Institutet Research Foundation - EFSD (EFSD Mentorship Programme supported by AstraZeneca) - German Research Foundation (SFB TRR 219, projects C1 and M1) - National Institute for Health Research (UK) (Clinician Scientist Award)

Introduction & Objective: Data on cardiovascular (CV) risk in patients with type 1 diabetes (T1D) is lacking. Our study aimed to assess coronary arteries in high-risk T1D patients using optical coherent tomography (OCT) to estimate their CV risk. Methods: Sixty-two patients with T1D &gt; 10 years, age 30-67 years, with no history of CVD were examined by carotid ultrasound and coronary artery calcium (CAC) score. Twelve patients were recognized as high-risk defined as CAC score &gt;400 and/or presence of ≥2 carotid plaques. Patients were subsequently examined by coronary angiography and OCT. Results: Mean age was 64.5±1.8 years, T1D duration 36±11.5 years, HbA1c 7.5±0.8 % and baseline LDL 88.9±21.3 mg/dl. Thin-cap fibroatheroma (TCFA [Figure-A]) was identified in 7/12 (58.3%) patients and very high-risk plaque (TCFA with lumen area &lt; 3.5 mm2 [B], lipid arch &gt; 180° and macrophages [C]) was present in 4/12 (33.3%) patients. We saw intraluminal thrombus [D] and cholesterol crystal [E] in 3/12 (25%) patients. A strong correlation between OCT stenosis and CAC score at the left anterior descending artery (Pearson’s r=0.75, p=0.005) was identified. Conclusion: Our study showed that asymptomatic T1D patients with high CAC score and carotid plaques had very severe OCT findings. We observed a significant proportion of high-risk lesions potentially associated with plaque rupture and risk of CV death. Disclosure M. Dubsky: None. R. Roland: None. N. Marhefková: None. P. Wohlfahrt: None. P. Novodvorsky: Speaker's Bureau; Sanofi, Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Novo Nordisk A/S. Research Support; Sanofi. Speaker's Bureau; Abbott, Medtronic, Berlin-Chemie AG, Viatris Inc., Novartis AG. V. Karmazin: None. M. Haluzik: Advisory Panel; Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Johnson & Johnson Medical Devices Companies. Consultant; Merck & Co., Inc., Sanofi, Novo Nordisk, Eli Lilly and Company, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Johnson & Johnson Medical Devices Companies, Novatin. Research Support; Sanofi. Speaker's Bureau; Sanofi, Novo Nordisk. M. Pazdernik: None. Funding Supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, Project No. LX22NPO5104) - Funded by the European Union - Next Generation EU.

Introduction: With increasing access to intermittently scanned continuous glucose monitoring (isCGM) , with the FSL, it is essential to understand the effect of TIR and TBR on HbA1c, DRD, and resource utilisation in people living with diabetes Methods: Clinicians from 1NHS UK hospitals submitted FSL user data for16,034 participants, (96% type 1 diabetes) of whom 6859 had follow-up data, collected during routine clinical care and submitted to a web-based secure tool. Linear regression analysis was used to estimate the age, gender and baseline HbA1c adjusted reduction in HbA1c in the TIR categories. Results: Follow up TIR data were available for 3250 (47%) participants of which, 1241 (38%) reported TIR in line with the international consensus (3.9-mmol/l) . After adjustments for age gender, baseline HbA1c and duration of diabetes follow-up TIR ≥50% was associated with an 0.8% (8.75 mmol/mol) reduction in HbA1c (P&lt;0.0001) and -0.29 reduction in DRD (P&lt;0.0001) , while follow-up TIR ≥70% was associated with a 1.3% (14.mmol/mol) reduction in HbA1c (P&lt;0.0001) and 0.40 reduction (P&lt;0.0001) in DRD vs. those with TIR &lt;50%. With the use of FSL, there was a 67% reduction in hospital admissions due to hypoglycaemia (none in those with TIR≥50) , a 63% reduction in hospital admissions related to hyperglycaemia/DKA and an 85% reduction in paramedic outcalls. The reduction in hospital admissions for hyperglycaemia/DKA and paramedic callouts was independent of the TIR achieved during follow-up. The incidence of severe hypoglycaemia was lower in those with TBR ≤5% as compared to those with TBR &gt;5% (7% vs. 11%) but was not statistically significant (P=0.31) . Conclusion: In a large cohort of UK FSL users, we demonstrate a significant reduction in HbA1c, diabetes-related distress and resource utilisation which was associated with improved TIR Disclosure H.Deshmukh: None. T.Sathyapalan: n/a. B.Pieri: None. E.G.Wilmot: Advisory Panel; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Sanofi, Research Support; Insulet Corporation, Novo Nordisk, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi. P.Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. N.Shah: None. V.Tsatlidis: None. A.N.Lumb: Advisory Panel; Abbott, Dexcom, Inc., Research Support; Abbott, Novo Nordisk, Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk. R.E.Ryder: None. C.Walton: None. Funding NIHR clinical lectureship

Hypoglycemia remains a major concern for persons with T1D using injections or “open loop” insulin pump delivery. Risk avoidance strategies are required, but often at the expense of increased hyperglycemia and elevated A1C levels. AID systems may reduce the need for human intervention by minimizing out-of-range glucose levels. We evaluated glycemic outcomes of people with T1D using the Omnipod 5 AID System, stratified by each user's time below range (TBR, % &lt;70 mg/dL) with their prior standard therapy (ST) . Participants of 3 age groups: 2-5.9, 6-13.9, and 14-70 years, with A1C&lt;10% used AID for 3 months at home after a 14-day ST phase. TBR and time in range (TIR, % 70-180 mg/dL) were evaluated across 3 ST TBR groups: ≤1%, &gt;1% to &lt;4%, and ≥4%. Trends were similar across all age groups. Overall, those with high ST TBR (≥4%) had a higher ST TIR (64.9%) ; AID substantially decreased TBR (-3.4%, -49 min/d) and increased TIR (73.9%) (Table) . Those with low ST TBR (≤1%) had lower ST TIR (50.8%) ; AID increased TIR substantially (to 67.9%) , while TBR was low (0.7%) . AID was associated with significant reductions in time below range in cohorts with high hypoglycemia risk (≥4% TBR) at baseline. In the lowest hypoglycemia risk at baseline cohort (≤1% TBR) , the median TBR remained ≤1%, although TBR was modestly higher, but this group had the largest increase in TIR. Disclosure G.P.Forlenza: Advisory Panel; Lilly, Medtronic, Consultant; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker's Bureau; Lilly Diabetes. C.J.Levy: Advisory Panel; Dexcom, Inc., Eli Lilly and Company, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, T1D Exchange, Tandem Diabetes Care, Inc. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. S.A.Macleish: Advisory Panel; Insulet Corporation. D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. A.Bhargava: Research Support; Abbott Diabetes, AbbVie Inc., Boehringer Ingelheim International GmbH, Boston Therapeutics, Inc., Covance, Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics, vTv Therapeutics. T.C.Jones: None. G.Aleppo: Consultant; Insulet Corporation, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Fractyl Health, Inc., Insulet Corporation, Novo Nordisk, Speaker's Bureau; Dexcom, Inc. B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker's Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. L.M.Huyett: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. T.T.Ly: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. Omnipod 5 research group: n/a. A.L.Carlson: Advisory Panel; MannKind Corporation; Employee; Bright Health Group; Other Relationship; Medtronic; Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk, Sanofi, UnitedHealth Group. Funding This study was funded by Insulet Corporation.

AID systems must accommodate a wide range of insulin requirements safely and effectively to apply to a broad population. We evaluated glycemic outcomes among people ages 2 to 70y with T1D and baseline A1C&lt;10% during a 3-mo home trial with the Omnipod 5 AID System, stratified by their baseline total daily insulin dose (TDD) during a 14-day standard therapy phase (ST, multiple daily injections or pump therapy) before AID use. No minimum TDD or weight was required to enter the study. Glycemic outcomes (time in range (TIR) 70-180 mg/dL, time below range (TBR) &lt;70 mg/dL, time above range (TAR) &gt;180 mg/dL) and change in TDD were evaluated across 6 ST TDD ranges, from &lt;10U to ≥65U, during AID compared with ST. Participants (N=320) had a ST TDD of (mean ± SD) 34.8±21.7U (range 5.3-166.0U) . TDD during AID ranged from 5.0 to 110.7U; TDD increased slightly for those using &lt;30U per day. TIR increased during AID across all TDD ranges (p&lt;0.05, Table) . TAR and TBR were reduced in groups with TDD ≥10U and TDD ≥20U, respectively. Multiple linear regression indicated that older age and higher TIR during ST (both p&lt;0.05) were associated with higher TIR during AID, while no relationship was found between ST TDD and TIR during AID (p=0.29, r2=0.57) . The Omnipod 5 System was safe and effective for a large cohort of people with T1D ages 2 to 70y across a wide range of insulin needs. Disclosure M.Schoelwer: Other Relationship; Dexcom, Inc., Research Support; Insulet Corporation, Medtronic, Tandem Diabetes Care, Inc. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. J.Sherr: Advisory Panel; Bigfoot Biomedical, Inc., Cecelia Health, Insulet Corporation, Medtronic, Vertex Pharmaceuticals Incorporated, Consultant; Insulet Corporation, Lexicon Pharmaceuticals, Inc., Research Support; Dexcom, Inc., Insulet Corporation, Jaeb Center for Health Research, JDRF, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Speaker's Bureau; Lilly Diabetes. C.J.Levy: Advisory Panel; Dexcom, Inc., Eli Lilly and Company, Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, T1D Exchange, Tandem Diabetes Care, Inc. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. S.A.Macleish: Advisory Panel; Insulet Corporation. D.Desalvo: Consultant; Dexcom, Inc., Insulet Corporation, Research Support; Insulet Corporation. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. A.Bhargava: Research Support; Abbott Diabetes, AbbVie Inc., Boehringer Ingelheim International GmbH, Boston Therapeutics, Inc., Covance, Dexcom, Inc., Eli Lilly and Company, Gan & Lee Pharmaceuticals, Insulet Corporation, Kowa Pharmaceuticals America, Inc., Lexicon Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Poxel SA, Quintiles, Sanofi, Senseonics, Tolerion, Inc., Viking Therapeutics, vTv Therapeutics. T.C.Jones: None. G.Aleppo: Consultant; Insulet Corporation, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Fractyl Health, Inc., Insulet Corporation, Novo Nordisk, Speaker's Bureau; Dexcom, Inc. B.W.Bode: Advisory Panel; CeQur SA, MannKind Corporation, Medtronic, Novo Nordisk, Zealand Pharma A/S, Consultant; Bigfoot Biomedical, Inc., Research Support; Abbott, Beta Bionics, Inc., Dexcom, Inc., Diasome, Dompé, Eli Lilly and Company, Insulet Corporation, IQVIA Inc., Jaeb Center for Health Research, Medtronic, Novo Nordisk, Provention Bio, Inc., REMD Biotherapeutics, Sanvita Medical, Senseonics, ViaCyte, Inc., Speaker's Bureau; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Xeris Pharmaceuticals, Inc., Stock/Shareholder; AgaMatrix, Glytec, LLC. R.E.Gurlin: Employee; Insulet Corporation. T.T.Ly: Employee; Insulet Corporation, Stock/Shareholder; Insulet Corporation. Omnipod 5 research group: n/a. A.L.Carlson: Advisory Panel; MannKind Corporation, Employee; Bright Health Group, Other Relationship; Medtronic, Research Support; Funding This study was funded by Insulet Corporation.

Behavioral health support can benefit those living with diabetes, but there is limited information on patient reported outcomes (PROs) associated with a virtual clinic. Adults with diabetes (n=234) received virtual care including support for CGM initiation and management over a 6-month study period. Care was led by a CDCES with support from a behavioral team. Participants completed PROs surveys 1) at baseline and 6 months to evaluate change and 2) each month on diabetes distress (DD), fear of hypoglycemia (FOH), and depression (DEP). Full list of PROs surveys included in table. A positive screen led to recommendation for a brief behavioral intervention. Participants with T1D (n=160) were 44(±14) years and mean baseline A1c of 7.8%. Participants with T2D (n=74) were 55(±12) years and mean baseline A1c of 8.1%. Participants screened positive for DD, FOH, or DEP 67% of the time with FOH as the most common concern. Of those with a positive screen, 70% of T1D and 59% of T2D participants had at least one behavioral team contact. Virtual clinic care was associated with a benefit on 7 of 9 PROs for T1D and 7 of 9 PROs for T2D (p values &lt; 0.05; see table). For these virtual clinic adults with diabetes, PROs improved 78% of the time with noteworthy benefits of less FOH, less DD, and more glucose monitoring satisfaction. Paired with the glycemic improvements observed in this virtual clinic study, there were robust benefits on the quality of life of adults with diabetes. Disclosure K.K.Hood: Consultant; Cecelia Health. S.Oser: Advisory Panel; Cecelia Health, Dexcom, Inc., Consultant; Medscape, Research Support; Abbott Diabetes. T.Oser: Advisory Panel; Cecelia Health, Consultant; Dexcom, Inc., Medscape, Research Support; Abbott. D.Raghinaru: None. Z.Thompson: None. R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. G.Aleppo: Advisory Panel; Medscape, Consultant; Bayer Inc., Insulet Corporation, Research Support; Dexcom, Inc., Eli Lilly and Company, Emmes, Insulet Corporation, Fractyl Health, Inc., WellDoc, Speaker's Bureau; Dexcom, Inc. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. T.L.Cushman: None. R.L.Gal: None. C.Kollman: Research Support; Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc. D.F.Kruger: Advisory Panel; Abbott Diabetes, Lilly, Medtronic, Novo Nordisk, Research Support; Dexcom, Inc., Beta Bionics, Inc., Speaker's Bureau; Dexcom, Inc., Lilly, Xeris Pharmaceuticals, Inc., Novo Nordisk. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. T.S.Mcarthur: None. B.A.Olson: Stock/Shareholder; Abbott. Funding The Leona M. and Harry B. Helmsley Charitable Trust; Dexcom, Inc.