Artykuły w czasopismach na temat „Novartis Campus”

Abstract Introduction Treatment of chronic phase (CP) chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) proved to be almost equally effective in young and elderly patients. Three TKIs, imatinib (IM), dasatinib (DAS) and nilotinib (NIL), are approved for frontline therapy in Italy. Choice of frontline TKI is based on a combined evaluation of patient's characteristics and expectations, with age usually playing a prominent role. However, to date, few data are available on patterns of TKI selection in very elderly patients. Aim To analyse the use of frontline TKI therapy in a large and unselected cohort of very elderly CP-CML patients Methods We retrospectively evaluated 332 patients aged ≥75 year diagnosed from 1/2012 to 12/2019 at 36 Hematology Centres participating at the "Campus CML" project. Results Clinical features at diagnosis for the whole cohort and according to frontline TKI are reported in Table 1. As to frontline TKI, 285 patients (85.8%) received IM and 47 (14.2%) a 2G-TKI (DAS n=28, 59.5%; NIL n=19, 40.5%). Of the 285 IM-treated patients, 192 (67.3%) started with standard dose (400 mg/day) and 93 (32.7%) with a reduced dose (300 mg/day n=64, 22.5%; <300 mg/day n=29, 10.2%). Among the 47 patients starting a 2G-TKIs, 35 (74.4%) received standard dose and 12 (25.6%) a reduced dose (NIL <600 mg/day n=3; DAS 80 mg/day n=4 and 50 mg/day n=5). There were no differences between patients treated with imatinib or 2G-TKI (Table 1); only a previous cerebrovascular event was reported in a significantly higher rate of IM-treated patients. It is however evident that the distinct toxicity profiles of NIL and DAS had an impact on TKI choice as, for example, no patient with diabetes or ischemic heart disease received NIL. Following widespread introduction of generic IM in Italy in early 2018, patients were divided in 2 groups: among 238 patients diagnosed from 2012 to 2017, 198 (83.1%) received IM and 40 (16.9%) a 2G-TKI, while patients diagnosed in 2018-2019 were treated with IM in 87/94 (92.5%) cases and with a 2G-TKI in 7 (7.5%) cases only (p=0.028). Conclusions IM remains the frontline drug of choice in very elderly CML patients, and this trend seems to increase after the introduction of the generic formulation. However, 2G-TKI are used in a small but sizeable group of patients, without a clear correlation with baseline CML features, thus probably reflecting a physician's evaluation of patient's fitness and/or expectation. Efficacy and safety of initial reduced TKIs doses in the setting of very elderly patients warrant further analyses. Figure 1 Figure 1. Disclosures Latagliata: Novartis: Honoraria; BMS Cellgene: Honoraria; Pfizer: Honoraria. Bonifacio: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Elena: CELGENE: Other: funding for meeting participation; PFIZER: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; GILEAD: Membership on an entity's Board of Directors or advisory committees. Iurlo: Novartis: Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Stagno: Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; InCyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding. Abruzzese: Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Breccia: Bristol Myers Squibb/Celgene: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria; Novartis: Honoraria.

Abstract Introduction. The recent spread of the COVID-19 infection has represented an important challenge in the management of acute lymphoblastic leukemia (ALL) patients. Aims and methods. To investigate the incidence, features, source of contagion and outcome of patients with ALL who developed a COVID-19 infection, a survey was conducted among 34 hematology centers throughout Italy within the Campus ALL network. The period covered by the survey spanned from February 2020 to April 2021 and included 756 adult ALL patients actively followed during this time period. Results. Sixty-three of the 756 ALL patients (8.3%) developed a COVID-19 infection, with an equal distribution among the various regions. The majority of cases (90.5%) was recorded during the second wave of the pandemic, between September 2020 and April 2021. The source of the infection was nosocomial in 26 cases (41.3%), familial in 23 (36.5%), unknown in 13 (20.6%) and work-related in 1 (1.6%). The infected patients were prevalently male (n=43, 68.2%) with a similar distribution among age groups: 21 patients aged 18-35 years, 17 35-50, 15 50-65 and 10 older than 65. Seventeen patients (27%) had a diagnosis of T-ALL, 28 (44.4%) of Ph- B-ALL and 18 (28.6%) of Ph+ ALL. Thirty-six (57.1%) of the infected patients had no concomitant comorbidities, whereas 27 (42.9%) had one or more comorbidities. The infection was documented at the onset of the disease in 4 patients (6.3%), during induction in 10 (15.9%), consolidation in 13 (20.6%), chemotherapy maintenance in 11 (17.5%), after allogenic transplant in 15 (23.8%), during maintenance with tyrosine kinase inhibitors (TKI) treatment or off-treatment in 8 (12.7%) and at relapse in 2 (3.2%). Of the infected patients, 9 were asymptomatic, 10 had only isolated fever, 36 had respiratory symptoms and 8 presented other symptoms, including - but not limited to - ageusia and anosmia. As a consequence, management of the infection was variable: 29 (46%) patients did not require hospitalization, 28 (44.4%) were hospitalized in a COVID ward and 13 of them required respiratory assistance; finally, 6 (9.5%) patients were transferred to an ICU. Importantly, in 54 patients (85.7%) there were no sequelae, in 1 patient a pulmonary fibrosis was documented and in 1 patient the delay in treatment led to a relapse of the disease, while 7 (11.1%) succumbed to the infection. Finally, in 6 cases (9.5%) the infection was still ongoing at the time of the survey, and at the last update (July 2021) it had resolved in all. Since a key aspect in the management of ALL is the adherence to the timing of treatment, we also investigated if COVID-19+ patients stopped treatment during the infection. Out of the 42 evaluable patients (patients who had undergone an allogeneic transplant or were off-treatment were excluded from this analysis), ALL treatment was suspended in 28 (66.6%). Importantly, while in Ph+ ALL only very few patients stopped treatment (3/12), in Ph- B-ALL the majority did interrupt it (18/22, p<0.001); likewise, also in T-ALL most patients suspended treatment (7/8). Conclusions. The incidence of SARS-CoV-2 infection in adult ALL patients in Italy over a 15 month period has been similar to that observed in the general population and has been recorded mostly during the second wave of the pandemic. The contagion was mainly nosocomial, suggesting that outward care should be pursued as much as possible in ALL. The infection was manageable, with 46% of patients not requiring any medical intervention and an overall death rate of 11%. Strikingly, in line with previous reports 1, it appears that Ph+ ALL patients were more manageable, with less treatment interruptions. These findings underline the advantage of the TKI-based induction/consolidation strategy without systemic chemotherapy in Ph+ ALL used in the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) protocols and further point to a possible protective role of TKIs in COVID-19-infected patients. Foà R et al, Br J Haematol. 2020;190(1):e3-e5 Disclosures Chiaretti: Incyte: Consultancy; novartis: Consultancy; pfizer: Consultancy; amgen: Consultancy. Bonifacio: Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Amgen: Honoraria. Marco: Jazz: Consultancy; Insight,: Consultancy; Janssen: Consultancy. Curti: Novartis: 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 Pharma: Membership on an entity's Board of Directors or advisory committees. Delia: Gilead: Consultancy; Amgen: Consultancy; abbvie: Consultancy; Jazz pharmaceuticals: Consultancy. Forghieri: Jannsen: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Jazz: Honoraria. Lussana: Amgen: Honoraria; Astellas Pharma: Honoraria; Pfizer: Honoraria; Incyte: Honoraria.

INTRODUCTION: Frontline therapy with second generation (2G) tyrosine-kinase inhibitors (TKIs) in chronic phase (CP) chronic myeloid leukemia (CML) patients demonstrated higher efficacy as compared to imatinib, with less patients experiencing treatment failure and progression to advanced disease. However, limited information are currently available on the management and outcome of those CML pts not achieving an optimal response to first-line treatment with a 2G-TKI. AIM: To describe the clinical outcome of CP CML patients without an optimal response to a frontline 2G-TKI that switched to alternative TKIs. METHODS: We performed a retrospective analysis in 22 Centers cooperating within the Italian CML Campus Project. Main inclusion criteria were: 1) diagnosis of CP-CML after 2010; 2) first-line treatment with a 2G-TKI; 3) switch to second-line treatment in case of non-optimal response (either following ELN recommendations or as for clinical practice); 4) CML in CP at the time of switching to second-line treatment. The main exclusion criteria were a switch to second-line treatment for intolerance or for low adherence to therapy. RESULTS: The main findings of this analysis are summarized in the table. Seventy-one pts meeting the inclusion/exclusion criteria were identified; the median age of pts at CML diagnosis was 46 (21-80) years. Sokal risk score was low, intermediate, and high in 24 (34%), 30 (42%), and 17 (24%) pts, respectively. First-line treatment was performed with nilotinib in 47 (66%) pts and dasatinib in 24 (34%) pts. According to the ELN 2020 recommendations, 51 (72%) pts fulfilled the criteria for "failure" and 20 (28%) pts those for "warning". BCR-ABL mutations were identified in 12 of 65 (18%) evaluable pts (T315I in 1 pt). Additional chromosomal abnormalities in Ph+ cells were identified in 6 of 54 (11%) evaluable pts. Second-line treatment was started after a median time of 16 (4-72) months, with ponatinib (40 pts, 56%), dasatinib (21 pts, 30%), nilotinib (7 pts, 10%), or bosutinib (3 pts, 4%). Median follow-up from start of second-line treatment was 25 (2-90) months. Best response to second-line treatment was MR2 in 18 (25%) pts and MR3 in 37 (51%) pts. Nineteen (27%) pts (13 for resistance and 6 for intolerance) switched to third-line treatment (ponatinib, 11 pts; nilotinib, 3 pts; dasatinib, 4 pts; imatinib, 1 pt), after a median time of 8 (1-72) months. Mutations were identified in 2 of 17 evaluable pts, and both patients harbored a T315I mutation. MR3 was reached by 9 (47%) of these pts. Lastly, 7 (10%) pts switched (6 for resistance and 1 for intolerance) to fourth-line treatment (asciminib, 4pts; dasatinib, 2 pts, nilotinib, 1 pt). Overall, 44 (62%) patients reached with sequential TKI treatments a MR3 (31/51 pts among "failures"; 13/20 among "warnings"). Allogeneic stem-cell transplantation (SCT) was performed in 7 (9.5%) pts (6 among "failures"), after a median time of 20 (15-60) months from CML diagnosis. Progression to advanced phase occurred in 2 (3%) pts; both pts previously met the ELN2020 "failure" criteria. Estimated 4-y PFS was 92.5%. Death occurred in 3 (4%) pts (1 after progression to blast phase, 2 for cardiovascular adverse events). Estimated 4-y OS was 93.7% CONCLUSION Our findings show that CP-CML patients not achieving an optimal response to frontline 2G-TKI therapy, despite a complex management, still have a favorable prognosis and survival due to the availability of both multiple TKI options and SCT. Figure Disclosures Gugliotta: Novartis: Honoraria; Incyte: Honoraria; Pfizer: Honoraria. Galimberti:Novartis: Speakers Bureau; Incyte: Honoraria. Abruzzese:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bms: Honoraria; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bocchia:CELGENE: Honoraria; Incyte: Honoraria. Castagnetti:Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Di Raimondo:Amgen, Takeda, Novartis: Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GILEAD, Incyte: Research Funding; GSK: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Cavo:Jannsen, BMS, Celgene, Sanofi, GlaxoSmithKline, Takeda, Amgen, Oncopeptides, AbbVie, Karyopharm, Adaptive: Consultancy, Honoraria. Rosti:Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau. Foà:Abbvie: 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; Janssen: 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; Novartis: Speakers Bureau; Incyte: Speakers Bureau. Saglio:Pfizer: Research Funding; Ariad: Research Funding; Roche: Research Funding; Incyte: Research Funding; Bristol-Myers Squibb: Research Funding; Novartis: Research Funding. Breccia:Abbvie: Consultancy; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Abstract Background Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML). However, the first months of therapy are crucial, as optimal response is defined as the achievement of molecular milestones at 3, 6 and 12 months (mo.) and as many toxicities, also causing a TKI switch, are more frequent in the 1st year. Methods To evaluate achievement of early molecular response (MR) and incidence of events leading to a TKI change during the 1st year of therapy, we retrospectively studied 1650 CP-CML patients diagnosed from 2012 and 2019 at 31 Hematology Centres and treated with frontline imatinib (IM) or second-generation (2G) TKIs dasatinib or nilotinib. Optimal MR at 3, 6 and 12 mo. were assessed according to 2020 ELN recommendations. Results Frontline TKI was IM in 926 (56.1%) and 2G-TKIs in 724 (43.9%) cases: the main clinical features at diagnosis of the entire cohort and according to frontline treatment is reported in the Table 1. Commonest comorbidities were arterial hypertension (38.7%), previous neoplasm (13.6%), diabetes (11.3%), peripheral vascular diseases (7.8%), COPD (7.5%) and ischemic heart disease (6.8%). IM-treated patients were older (p<0.001), with higher ELTS score (int/high 47.6% vs 35.6%, p<0.001) and more comorbidities (p<0.005 for all diseases). Optimal MR was achieved at 3 mo. by 1186/1430 (82.9%), at 6 mo. by 1025/1352 (75.8%) and at 12 mo. by 826/1264 patients (65.3%), respectively. Total number of patients discontinuing TKI in the 1st year was 321/1650 (19.4%), being higher with IM (237/926, 25.5%) than 2G-TKIs (84/724, 11.6%) (p<0.001). Main causes were primary resistance (8.7%, 12.3% IM vs 4.2% 2G-TKIs, p<0.001), extra-hematologic toxicity (6.4%, 8.2% IM vs 4.2% 2G-TKIs, p>0.001), hematologic toxicity (1.7%, 2.0% IM vs 1.4% 2G-TKIs, p=0.25) and progression (1.0%, 1.2% IM vs 0.8% 2G-TKIs, p=0.56). Cumulative incidence of discontinuation at 3, 6 and 12 mo. were 5.6%, 10.7% and 19.3%, respectively; values for IM and 2G-TKIs at the three timepoints were 8.1%, 15.0%, 25.5% and 2.5%, 5.3%, 11.5% (p<0.001) (Fig. 1). Conclusions This real-world study on over 1600 CML patients shows that almost 20% discontinue frontline TKI during the 1st year, mostly for primary resistance or toxicity. Discontinuation rates are higher with IM compared to 2G-TKIs, mostly at 3 mo. and are probably due to a lower attainment of early MR. The impact of older age, higher risks and heavier burden of comorbidities in IM patients should be considered and need deeper investigation. Figure 1 Figure 1. Disclosures Elena: GILEAD: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; PFIZER: Membership on an entity's Board of Directors or advisory committees; CELGENE: Other: funding for meeting participation. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Stagno: InCyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Other: Support for attending meetings and/or travel; Novartis: Consultancy, Honoraria, Other: Support for attending meetings and/or travel, Research Funding. Iurlo: Pfizer: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Bonifacio: Novartis: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Bristol Myers Squibb: Honoraria. Breccia: Pfizer: Honoraria; Incyte: Honoraria; Abbvie: Honoraria; Bristol Myers Squibb/Celgene: Honoraria; Novartis: Honoraria. Latagliata: Novartis: Honoraria; Pfizer: Honoraria; BMS Cellgene: Honoraria.

Abstract Blinatumomab (Blina) and inotuzumab (InO) have improved the outcome of relapsed/refractory B-lymphoblastic leukemia (R/R B-ALL). However, many patients (pts) relapse after these treatments and little is known on their outcomes after recurrence and re-treatment with subsequent immunotherapy. We hereby describe the clinical characteristics and outcome of 71 pts with R/R B-ALL treated with both Blina and InO in any sequence - Blina/InO or InO/Blina - at different disease recurrences. At diagnosis, the median age was 34 years (15-64) and the male/female ratio was 1.6. Sixteen pts (22%) were Ph+ ALL, 3 (4%) were t(4;11)+ and 9 (13%) carried a complex karyotypes. ECOG PS was 0-1 in 66 pts (93%). At the time of the first immunotherapy, pts had received a median of 2 previous lines of treatment (1-8). All Ph- pts received intensive chemotherapy front-line; Ph+ pts received TKIs and steroids in 13 cases and intensive chemotherapy plus TKIs in 3 cases. Blina was the first salvage treatment (Blino/InO sequence) in 57 pts (80%) and InO (InO/Blina sequence) in 14 (20%). Twenty-seven pts (38%) had underwent a previous allogeneic hematopoietic stem cell transplantation (HSCT). At the start of Blina as first immunotherapy, the median bone marrow (BM) blast count was 40% (0-100%); at the start of InO as first immunotherapy, the median BM blast count was 64% (2-90%). An extramedullary involvement was present in 5 patients (9%) in the Blina/InO group and in 1 patients (7%) in the InO/Blina group. During immunotherapy, the median number of lumbar punctures was 2 (0-9). A median of 2 cycles were administered for both Blina (range 1-9) and Ino (range 1-4). In the Blina/InO group, after Blina a G3/4 toxicity occurred in 15 cases (26%): non-hematologic in 12 cases (21%), neurologic in 6 (8%). Infections occurred in 17 pts (30%). In the InO/Blina group, after InO a G3/4 toxicity occurred in 3 pts (21%), with extra-hematologic toxicity in 2 cases (14%, liver toxicity 1 case). Infections occurred in 4 cases (28%). In the Blina/InO group, after Blina 36 pts (63%) achieved a complete remission (CR), with a negative minimal residual disease (MRD) in 24 (42%) pts; after InO, a CR was re-achieved in 47 pts (82.4%), with 34 (59.6%) being MRD-. In the InO/Blina group, after InO a CR was reached in 13 cases (93%), with 6 pts (42.8%) being MRD-; after Blina, a CR was re-achieved in 6 pts (42.8%), with 3 (21.4%) being MRD-. This salvage immunotherapy strategy represented a bridge to alloHSCT for 26 pts (37%). From the first immunotherapy, in the Blina/InO group, the median overall survival (OS) was 19 months and after InO 6.3 months (OS in MRD- vs MRD+, p ns). Disease free survival (DFS) after Blina was 7.4 months (11.6 vs 2.7 months in MRD- vs MRD+ pts, p .03) and after InO it was 5.4 months (MRD- vs MRD+ pts, p ns). In the InO/Blina group, the median OS was 9.4 months and after Blina 4.6 months (7.5 vs 2.8 months in MRD- vs MRD+ pts, p .02). DFS after InO was 5.1 months (MRD- vs MRD+ pts, p ns) and after Blina it was 1.5 months (8.7 vs 2.5 gg in MRD- vs MRD+ pts, p .02). OS and DFS in MRD- pts after Blina was significantly better, both in the Blina/InO and the InO/Blina groups. With a median follow-up of 16.5 months from the start of immunotherapy and 33.8 months from initial diagnosis, 24 pts (34%) are alive and 16 (22%) are alive in CR. Four patients (6%) died in CR due to veno-occlusive disease during HSCT after InO treatment. Interestingly, OS and DFS from the first immunotherapy was better in pts with a previous alloHSCT (median survival 24.2 vs 13 months, p=.0135). AlloHSCT after second immunotherapy was associated with a better OS and DFS (OS 9.8 and DFS 7.2 months vs 7.8 and 4.4 months, p ns). Our real-life study in R/R B-cell ALL pts with multiple previous lines of treatment demonstrates the feasibility and efficacy of a sequential immunotherapy strategy in terms of MRD response, DFS and OS, and as a bridge to HSCT. SM and PC: equal contributors Disclosures Papayannidis: Janssen: Honoraria; Astellas: Honoraria; AbbVie: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Curti: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Chiaretti: amgen: Consultancy; pfizer: Consultancy; novartis: Consultancy; Incyte: Consultancy. Forghieri: Jannsen: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Jazz: Honoraria. Bonifacio: Bristol Myers Squibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Cerrano: Janssen: Honoraria; Insight: Honoraria; Jazz: Honoraria. Fracchiolla: Gilead: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background. The Philadelphia (Ph) chromosome (chr.) is the hallmark of chronic myeloid leukemia (CML) and typically results from the reciprocal translocation t(9;22)(q34;11.2). Complex variant translocations (CVT) involving one or more additional chr. are identified in less than 5% of newly diagnosed CML. There are conflicting reports about the prognostic impact of CVT in the achievement of optimal response to tyrosine kinase inhibitor (TKI), and very few studies addressed the role of frontline treatment with imatinib or second generation (2G)-TKI in patients with CVT. Aims. To assess the response to imatinib or 2G-TKI in a large cohort of newly diagnosed CML with CVT, and to explore the impact of the different chr. translocations on outcome. Methods. This observational retrospective study was conducted in 19 hematologic centers in the framework of Campus CML, a network of Italian physicians involved in the management of CML patients. All newly diagnosed CML from 2000 to 2019 were evaluated and patients with CVT were selected for the present analysis. Karyotypes were defined according to the 2016 International System for Human Cytogenetic Nomenclature. Responses to frontline treatment were retrospectively categorized according to the 2013 ELN recommendations, as they include cytogenetic milestones. Deep molecular response (DMR, i.e. MR4or better) was defined as BCR-ABLIS ratio ≤0.01% or undetectable disease with ≥10,000 ABL copies. Patients with DMR lasting ≥2 years and at least a Q-PCR test every 6 months were defined as stable DMR responders. Failure-free survival (FFS) was calculated from the start of frontline TKI treatment to progression to advanced phase, death, or switch to other treatments for resistance. For FFS calculation, patients were censored at TKI stop for treatment-free remission (TFR) or in case of switch for intolerance only. Differences between subgroups according to the partner chr. were presented for descriptive purposes. Results. CVT were identified in 109 (3.2%) patients from a whole population of 3,361 subjects with newly diagnosed CML. Ninety-five out of 109 patients (87%) exhibited three-way translocations, with chr. 1, 4, 6, 10, 11, 12, 14, 15 and 17 representing the most common additional partners (figure). Four- and five-way translocations were identified in 13 and 1 patients, respectively. Additional chr. abnormalities (ACA) in the Ph+ cells were observed in 15/109 (13.8%) patients and were more common in older individuals (p=0.018). Overall, median age at diagnosis was 50.6 years (range 20-90). Risk distribution according to the ELTS score was 54%, 28% and 8% for L, I and H risk, respectively (10% missing). Cytogenetic result was available before the choice of frontline treatment in 45% of cases and represented a decisive factor in 28% of them (i.e. clinicians selected a 2G-TKI or high-dose imatinib, according to the available options). Frontline TKI treatment was imatinib in 80 cases (73%) and 2G-TKI (nilotinib n=22, dasatinib n=6, bosutinib n=1) in the remaining cases. The frequency of optimal response at 3, 6 and 12 months was 48%, 45% and 53%, respectively, for imatinib-treated patients, and 76%, 83% and 76%, respectively, for the 2G-TKI cohort (p<0.05 for all comparisons). Stable DMR was achieved by 39% of patients and 42% of them attempted a TFR. After a median follow-up of 91.3 months (range 1-236), 5-year FFS was 66% (95%CI: 53.4-76.4) and 84% (95%CI: 62.4-93.6) for imatinib and 2G-TKI treated patients, respectively (p=ns). The estimated 10-year OS for the entire cohort was 84.4% (95%CI: 73.6-91). The subtype of CVT had an impact on response and long-term outcome. Patients with CVT involving chr. 1, 4, 6, 11 or 12 had a higher frequency of MMR at 12 months than patients with CVT involving chr. 10, 14, 15 or 17 (75.8% vs 30.4%, respectively, p=0.001), higher frequency of stable DMR (48.7% vs 22.2%, respectively; p=0.04) and tended to have better median FFS (p=0.07), regardless of the type of frontline TKI and of the ELTS score. Conclusions. Due to its retrospective nature, this study does not allow to define which is the optimal therapy for CML harboring CVT at diagnosis. However, our data reinforce the usefulness of bone marrow karyotyping in CML. The observed differences between partner chr. may also depend on the breaking points, which are variable. Further dissection of CVT will help to identify which are associated to a poor response to TKIs. Figure Disclosures D'Adda: Incyte: Other: Advisory board; Novartis: Other: Advisory board; Pfizer: Other: Advisory board. Galimberti:Novartis: Speakers Bureau; Incyte: Honoraria. Crugnola:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Novartis: Honoraria. Bocchia:Incyte: Honoraria; CELGENE: Honoraria. Krampera:Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Breccia:Incyte: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Saglio:Novartis: Research Funding; Ariad: Research Funding; Pfizer: Research Funding; Bristol-Myers Squibb: Research Funding; Incyte: Research Funding; Roche: Research Funding.

Introduction : therapy of chronic phase (CP) chronic myeloid leukemia (CML) is based on tyrosine kinase inhibitors (TKIs) in virtually all patients. Three TKIs are approved for first-line therapy in Italy: imatinib and two second-generation (2G) TKIs, dasatinib and nilotinib. Choice of the front-line TKI is based on a combined evaluation of patient's and disease characteristics, age, risk, comorbidities and concomitant medications. Treating physician's preference and, in some cases, economic considerations, particularly after the advent of generic imatinib, may play a role in TKI selection. However, to date, few data are available on TKI use in a whole nation and on the possible drivers of treatment choice. Aim of the present work was to analyse the use of front-line TKI therapy in a large, unselected cohort of Italian CP-CML patients, correlating patient's features to drug choice. Methods: in the framework of the national Campus CML program, we retrospectively evaluated 1422 patients with CP-CML diagnosed from 2012 and 2019 in 21 haematologic Centres, mostly in academic and/or tertiary hospitals, widespread through the entire Italian territory and treated frontline with imatinib, dasatinib or nilotinib. Results: median age at diagnosis was 59.9 years [interquartile range (IQR) 47.1 - 71.7], with 317 (22.3%) patients under 45 years, 552 (38.8%) between 45 and 65 years and 553 (38.9%) older than 65 years; 821 (57.7%) patients were males. Among 1364 evaluable patients, CML risk according to Sokal score was low in 540 (39.6%), intermediate in 610 (44.7%) and high in 214 (15.7%) patients respectively; the number at low, intermediate or high risk according to the novel ELTS score among 1325 evaluable patients was 759 (57.3%), 402 (30.3%) and 164 (12.4%) respectively. Considering comorbidities, 1003 (70.6%) patients had at least one active disease at the time of CML diagnosis, the most common being hypertension (n=547, 38.5%), previous neoplasms (n=185, 13.0%), diabetes (n=150, 10.6%), chronic bronchopulmonary diseases (n=114, 8.0%), acute myocardial infarction (n=95, 6.7%), previous stroke (n=36, 2.5%) and other vascular diseases (n=98, 6.9%). Among 1335 evaluable patients, 813 (60.9%) were taking at least one concomitant medication, with 280 (21.0%) taking 3-5 drugs and 140 (10.5%) taking 6+ drugs at time of TKI start. As to the frontline therapy, 794 (55.8%) received imatinib and 628 (44.2%) were treated with 2G-TKIs, (226 dasatinib and 402 nilotinib) respectively. According to age, 2G-TKIs were chosen for majority of patients aged <45 (69.1%) while imatinib was used in 76.9% of patients over 65 (p<0.001). There was a predominance of imatinib use across all Sokal (51.1% in low, 61.3% in intermediate and 51.4% in high) and ELTS (50.3% in low, 60.4% in intermediate and 66.5%) risk categories. We observed a prevalent use of 2G-TKIs in patients presenting with higher WBC counts (55.1% if WBC >100,000/mm3 vs 38.2% if WBC <100,000/mm3; p<0.001), lower Hb (53.8% if Hb <10 g/dl vs 41.9 if Hb >10 g/dl; p=0.001) and bigger spleen (65.1% if spleen >5 cm vs 44.8% if spleen 1-5 cm vs 37.3% if spleen not palpable; p<0.001). There was a decreasing use of 2G-TKIs with higher number of concomitant drugs: 64.4% for 0, 47.7% for 1-2, 27.0% for 3-5 and 13.6% for >5 drugs, respectively (p<0.001). Concordantly, there was a significant higher use of imatinib in patients with hypertension (69.8%), diabetes (70.0%), COPD (73.7%), previous neoplasms (73.0%), AMI (86.3%) or stroke (97.2%) history (p<0.001 for all conditions). Lastly, we observed a wider use of imatinib (61.1%) in patients diagnosed in years 2018-19, compared to those of the period 2012-17 (53.7%; p=0.01). In multivariable analysis, factors correlated with imatinib use were age > 45 years, intermediate or high Sokal risk, presence of some comorbidities (2nd neoplasia and stroke) and number of concomitant medications. Conclusions: preliminary results of this observational study on almost 1500 patients show that around 55% of newly diagnosed Italian CP-CML patients receive imatinib as front-line therapy, and that the use of 2G-TKI is prevalent in the younger patients and in those with no concomitant clinical conditions. The counterintuitive finding of imatinib prevalence as frontline treatment in high risk patients might be explained by the older age of these patients. Introduction of the generic formulation in 2018 seems to have fostered the use of imatinib. Figure Disclosures Breccia: Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Abbvie: Consultancy; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria. Cavazzini:Pfize: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Saglio:Bristol-Myers Squibb: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Ariad: Research Funding; Roche: Research Funding.

Novel therapies targeting BTK (ibrutinib), PI3Kδ (idelalisib) and BCL2 (venetoclax) are active in poor-risk chronic lymphocytic leukemia (CLL) and are widely administered to patients with relapsed/refractory (R/R)-CLL. Given the activity of ibrutinib in high-risk CLL patients, including those with del17p/TP53 mutation or germline IGHV genes, we assumed that this drug could diminish the prognostic utility of the CLL-IPI, because the outcome of patients with high- and very high-risk CLL-IPI scores may improve. Recently, Soumerai et al (Lancet Hematology, 2019) proposed a new risk score for overall survival (OS) based on four accessible markers, called BALL (β2-microglobulin, anemia, LDH, last therapy), in the setting of R/R-CLL patients receiving chemo-immunotherapy or targeted therapies in clinical trials. This model segregates CLL patients into three groups with significantly different OS. This multicenter, observational retrospective study aimed at validating the proposed BALL score for R/R-CLL real-world patients treated with ibrutinib. The primary objectives were to determine whether: i) the BALL score is of prognostic value for ibrutinib R/R-CLL patients, ii) the BALL score is predictive of progression-free survival (PFS); and iii) the CLL-IPI retains its prognostic power also in R/R patients treated with ibrutinib. This study, from an institutional Italian multicenter working group on CLL ('Campus CLL'), included CLL patients collected from 18 Italian centers and 1 Israeli center, who received ibrutinib 420 mg/day outside of clinical trials as salvage therapy with available data for the calculation of the BALL and CLL-IPI scores at the time of the start of treatment. OS was estimated for all subgroups according to both scores. Additionally, risk-specific PFS was assessed. Kaplan-Meier curve, log-rank test and Cox regression analyses were performed. The prognostic accuracy of the predictive model was assessed by the Harrell's C-index. Overall, 541 CLL patients were included in this analysis. The majority of patients were Binet stages B and C (87.2%). The median age was 70.4 years (range 37 - 88) and 353 cases (65.2%) were male. The median number of previous therapies was 2 (range 1-9). The baseline patients' features are listed in Table 1. After a median follow-up of 1.8 years (range 1 month to 5.8 years), 101 patients had died and 206 experienced an event (death or progression). According to the BALL score, 372 patients (68.8%) were classified as low-risk, 132 (24.4%) as intermediate-risk and 37 (6.8%) as high-risk. Stratification of patients according to the BALL score predicted significant differences in terms of OS. Thus, low-risk patients had a 2-year OS probability of 89.2% (HR=1), intermediate-risk of 79.9% (HR=2.8, 95%CI 1.8-4.4, P<0.0001) and high-risk of 48.2% (HR=6.6, 95%CI 3.9-11, P<0.0001) (Figure 1). The C-statistic was 0.66 (P<0.001) for OS prediction. The CLL-IPI score indicated that 32 patients (5.9%) were classified as low-risk, 123 (22.7%) as intermediate-risk, 252 (46.6%) as high-risk and 134 (24.8%) as very high-risk. Stratification of patients according to the CLL-IPI score did not allow to predict significant differences in OS. Indeed, low-risk patients had a 2-year OS probability of 92.7% (HR=1), intermediate-risk patients of 88.4% (HR=2.3, 95%CI 0.5-9.9, P=0.26), high-risk of 84% (HR=3.3, 95%CI 0.8-13.7, P=0.1) and very high-risk of 76.4% (HR=4.3, 95%CI 1.038-17, P=0.046). Both the BALL and CLL-IPI scores failed to stratify patients significantly in terms of PFS. Our multicenter retrospective study confirms the prognostic power of the BALL score in this real-world series of R/R-CLL patients treated with ibrutinib, as previously reported in the setting of clinical trials (Soumerai et al, Lancet Hematology 2019). Furthermore, the CLL-IPI did not retain a discriminative power in the current retrospective study of ibrutinib-treated patients, possibly due to i) the well-known activity of ibrutinib in high-risk CLL patients, i.e. those with TP53 disruption and/or germline IGHV genes, which represent the most heavily weighted adverse risk factors contributing to the CLL-IPI, and to ii) the fact that the CLL-IPI was designed for patients receiving front-line chemo-immunotherapy. Conversely, the BALL score may identify higher risk R/R-CLL patients potentially requiring alternative and more effective therapeutic strategies. Disclosures Mauro: Jannsen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Shire: Consultancy, Research Funding; Roche: Consultancy, Research Funding. Coscia:Gilead: Membership on an entity's Board of Directors or advisory committees; Karyopharm Therapeutics: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees. Herishanu:Roche: Honoraria; Janssen: Honoraria; AbbVie: Honoraria. Varettoni:ABBVIE: Other: travel expenses; Roche: Consultancy; Gilead: Other: travel expenses; Janssen: Consultancy. Rigolin:AbbVie: Speakers Bureau; Gilead: Speakers Bureau; Gilead: Research Funding. Rossi:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria, Other: Scientific advisory board; Janseen: Honoraria, Other: Scientific advisory board; Roche: Honoraria, Other: Scientific advisory board; Astra Zeneca: Honoraria, Other: Scientific advisory board. Gaidano:AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sunesys: Consultancy, Honoraria; Astra-Zeneca: Consultancy, Honoraria. Cuneo:Amgen: Honoraria; Abbvie: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau. Foà:Roche: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Speakers Bureau; Amgen Inc.: Consultancy, 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; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Novartis: Consultancy, 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; Shire: Consultancy, 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; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees.

Abstract HER2Pro: A Phase 1b dose de-escalation study of high dose prochlorperazine added to paclitaxel, trastuzumab and pertuzumab in patients with previously untreated HER2-positive metastatic breast cancer Authors Teesha Downton1,2, Emma Karlsen1, Katharine Cuff3,4, Euan Walpole3,4, Fiona Simpson3,4, Elgene Lim1,2. Affiliations 1Garvan Institute of Medical Research, Darlinghurst NSW, Australia; 2School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales Sydney, Australia; 3Diamantina Institute, University of Queensland, Woolloongabba QLD, Australia; 4Princess Alexandra Hospital, Brisbane QLD, Australia Disclosures T. Downton: None. E. Karlsen: None. K. Cuff: None. E. Walpole: None. F. Simpson: None. E. Lim. Advisory Board for Pfizer, Astra Zeneca, Lilly, Roche, Novartis, Gilead Australia. Research Funding from Pfizer, Novartis, Bayer. Abstract Background: The anti-emetic prochlorperazine reversibly inhibits dynamin-mediated endocytosis. Preclinical studies have demonstrated that through this mechanism, high dose prochlorperazine can temporarily increase tumor cell antigen presentation, enhance interaction of tumor antigens with therapeutic monoclonal antibodies, and improve antibody-dependent cellular cytotoxicity (Chew H et al. Cell 2020). High dose prochlorperazine has been well tolerated and proof of mechanism demonstrated in a pilot study (ACTRN12619001051134), and in a phase Ib trial (ACTRN12619001527156) of prochlorperazine with cetuximab in patients with EGFR-expressing advanced head and neck squamous cell carcinoma or breast cancer. Prochlorperazine potentially offers a novel approach to improve the efficacy of a range of therapeutic antibodies. This study HER2Pro (ACTRN12622000016730) aims to evaluate the feasibility and safety of high dose prochlorperazine in combination with paclitaxel, trastuzumab, and pertuzumab in patients with HER2-positive metastatic breast cancer. Trial Design: In this phase Ib single-arm trial, patients receive standard of care trastuzumab and pertuzumab 3-weekly and paclitaxel weekly. From cycle 2, patients in addition receive de-escalating doses of prochlorperazine weekly for 6 weeks, though an additional 6 weeks may be given if there are no treatment associated serious adverse events. Dose de-escalation will be evaluated using a 3+3 design, commencing at a prochlorperazine intravenous dose of 0.8mg/kg weekly. Eligibility: Eligible patients must have previously untreated HER2-positive metastatic breast cancer, Eastern Cooperative Oncology Group performance status 0-1, and baseline left ventricular ejection fraction 50%. Key exclusion criteria include current daily treatment with corticosteroids at a dose &gt;10mg prednisolone or equivalent, blood pressure &lt; 90/50 mmHg, prolonged QT interval, and Parkinson’s disease. Objectives: The primary objective is to determine the recommended phase 2 dose. Secondary objectives include determining the frequency and severity of adverse events, rates of cardiotoxicity, objective response rate, duration of response and progression free survival. Tertiary objectives include analysis of receptor trafficking and immune system activation on paired tumor biopsies obtained before and after first prochlorperazine dose. Accrual: 6-12 patients will be enrolled across 2 Australian sites. Enrollment for this trial is expected to commence late 2022. Citation Format: Teesha Downton, Emma Karlsen, Katharine Cuff, Euan Walpole, Fiona Simpson, Elgene Lim. HER2Pro: A Phase 1b dose de-escalation study of high dose prochlorperazine added to paclitaxel, trastuzumab and pertuzumab in patients with previously untreated HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-10-05.

Abstract WinPro: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early-stage hormone receptor-positive breast cancer Authors Teesha Downton1,2,3, Davendra Segara3, Andrew Ong4, Janne Bingham5, Emma-Kate Carson4, Julia Chen1,2,3, Kate Middleton3, Geoffrey Lindeman6, Andrew Parker3, Elgene Lim1,2,3. Affiliations 1Garvan Institute of Medical Research, Darlinghurst NSW, Australia; 2School of Clinical Medicine, St Vincent’s Healthcare Clinical Campus, Faculty of Medicine and Health, University of New South Wales Sydney, Australia; 3St Vincent’s Hospital Sydney, Darlinghurst NSW, Australia; 4Campbelltown Hospital, Campbelltown NSW, Australia; 5Royal Adelaide Hospital, Adelaide SA, Australia; 6Walter & Eliza Hall Institute of Medical Research, Parkville VIC, Australia Disclosures T. Downton: None. D. Segara: None. A. Ong: None. J. Bingham: None. E. Carson: None. J. Chen: None. K. Middleton: None. G. Lindeman: None. A. Parker: None. E. Lim: Advisory Board for Pfizer, Astra Zeneca, Lilly, Roche, Novartis, Gilead Australia. Research Funding from Pfizer, Novartis, Bayer. Abstract Background: Preclinical studies have observed that progesterone has inhibitory effects on the estrogen-stimulated growth of estrogen receptor (ER)-positive, progesterone receptor (PR)-positive breast cancer. Mohammed H et al. (Nature 2015) identified that activated PR associates with the ER and modulates the interactions of the ER with chromatin, with a shift towards the transcription of genes associated with apoptosis and differentiation, and away from genes associated with proliferation. We hypothesize that the addition of prometrium, a microionized progesterone, may enhance the anti-proliferative effects of standard endocrine therapy in women with ER-positive PR-positive breast cancer. Trial Design: WinPro (NCT03906669) is an ongoing multicenter, phase II, randomized, open-label, window of opportunity study comparing the effect on standard endocrine therapy with or without prometrium on breast cancer cell proliferation. The study population is postmenopausal women with early-stage operable breast cancer where the tumor is ≥5mm on imaging, ER ≥10%, PR≥10%, and HER2-negative. Patients currently on hormone replacement therapy or the oral contraceptive pill, or who have a history of endometrial cancer or venous thromboembolism are not eligible. Patients are randomized 1:1:1 to letrozole 2.5mg daily, letrozole 2.5mg + prometrium 300mg daily, or tamoxifen 20mg + prometrium 300mg daily. Allocated treatment is taken for 14 days prior to surgery. Primary surgery and adjuvant treatment is as per standard of care. Objectives: The primary objective is to compare the geometric mean suppression of centrally assessed Ki67 between the diagnostic biopsy sample (pre-treatment) and the surgical sample (post-treatment). The secondary objective is to evaluate safety and tolerability. Tertiary objectives include defining genes predictive of a reduction in Ki67, and evaluating the changes in ER, PR, AR, FoxA1, Cyclin D1, and apoptotic markers in breast tumors post-intervention. Accrual: This study opened in February 2018 and as of 13 July 2022, 164 patients have been enrolled. Target accrual is 200 patients. Contact information: This study is led at St Vincent’s Hospital Sydney, Australia, and funded by the Cancer Council of NSW and the NHMRC Translational Breast Cancer Project grant. Contact: Elgene Lim MBBS FRACP PhD at e.lim@garvan.org.au. Citation Format: Teesha Downton, Davendra Segara, Andrew Ong, Janne Bingham, Emma-Kate Carson, Julia Chen, Kate Middleton, Geoffrey Lindeman, Andrew Parker, Elgene Lim. WinPro: A window of opportunity study of endocrine therapy with and without prometrium in postmenopausal women with early-stage hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-10.

Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020; Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects. Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts. CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. &lt;6), CLL treatment history, details regarding COVID-19 course, management, and therapy, and vital status were collected. The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies; univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx). Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98); 31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2). Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L; 27% vs. 21%), and lymphocytopenia (ALC &lt; 1.0 x 109/L; 18% vs. 28%), while others varied between Co1 and Co2 (p&lt;0.0001), including cough (61% vs. 93%), dyspnea (60% vs. 84%), fatigue (13% vs. 77%). Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p&lt;0.0001). Figure 1 depicts OS in each cohort. Univariable analyses demonstrated that age and CIRS ≥6 significantly predicted inferior OS in both cohorts, while only age remained an independent predictor of inferior OS in multivariable analyses (Table 2). Prior treatment for CLL (vs. observation) predicted inferior OS in Co1 but not Co2. Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including therapeutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts; COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented. Disclosures Roeker: American Society of Hematology: Research Funding; Abbott Laboratories: Other: spouse with minority ownership interest ; AbbVie: Other: spouse with minority ownership interest . Scarfo:Janssen: 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, Speakers Bureau; AstraZeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. Eyre:AbbVie: Consultancy, Honoraria, Other: travel support; Gilead: Consultancy, Honoraria, Other: travel support; Janssen: Consultancy, Honoraria, Other: travel support; KITE, AZ, Loxo Oncology at Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Muntañola Prat:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards. Villacampa:AstraZeneca: Other: advisory role; Merck Sharp & Dohme: Honoraria. Leslie:AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: 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; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Speakers Bureau; Karyopharm: Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Allan:Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy; Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria. Furman:Incyte: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Pharmacyclics: Consultancy; Loxo Oncology: Consultancy; Oncotarget: Consultancy; Janssen: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Verastem: Consultancy. Pagel:BeiGene, Astrazeneca, Loxo Oncology, Gilead: Consultancy. Hernandez-Rivas:Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Patel:Genentech: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy; Janssen: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Motta:Roche: Honoraria; Janssen: Honoraria. Lamanna:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Verastem: Research Funding; Bei-Gene: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Vitale:Janssen: Honoraria. Kamdar:Roche: Research Funding. Österborg:BeiGene: Research Funding; Kancera: Current equity holder in publicly-traded company, Research Funding; Sanofi: Consultancy; Karolinska Univeristy Hospital, Stockholm, Sweden: Current Employment. Hanson:Janssen-Cilag: Research Funding; Gilead: Research Funding; AbbVie: Honoraria. Eichhorst:ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding. Reda:Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Varettoni:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses; AbbVie: Other: Travel/accommodations/expenses; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees. Marchetti:Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Other: Sponsored meetings; Takeda: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings. Munir:F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland; Alexion: Honoraria. Zabalza:Janssen: Honoraria, Other: travel grants; Roche: Other: travel grants; Novartis: Other: travel grants. Janssens:Amgen: Consultancy, Other: travel grants; speaker fees; Abbvie: Consultancy, Other: travel grants; speaker fees; Celgene: Consultancy, Other: travel grants; speaker fees; Janssen: Consultancy, Other: travel grants; speaker fees; Gilead: Consultancy, Other: travel grants; speaker fees; Novartis: Consultancy, Other: travel grants; speaker fees; Sanofi-Genzyme: Consultancy, Other: travel grants; speaker fees; Roche: Consultancy, Other: travel grants; speaker fees. Niemann:AstraZeneca: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Sunesis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Danish Cancer Society: Honoraria, Research Funding; Novo Nordisk Foundation: Honoraria, Research Funding. Perini:Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Abbvie: Speakers Bureau. Patten:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Honoraria. Marasca:Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Honoraria. Iyengar:Janssen: Honoraria; Gilead: Honoraria. Ferrari:Abbvie: Honoraria. El-Sharkawi:Roche: Other: Conference fees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Itchaki:Abbvie Inc: Consultancy, Research Funding. Ma:Novartis: Research Funding; Juno: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Bioverativ: Consultancy, Honoraria; BeiGene: Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; TG Therapeutics: Research Funding. Van Der Spek:AMGEN: Other: Teaching activities. Seymour:Seattle Genetics: Research Funding; Merck: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding. Rigolin:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mauro:Roche: Other; Octopharma: Other; Takeda-Shire: Other; Gilead: Other; Janssen: Other; Abbvie: Other. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Levin:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation. Špaček:Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Walewska:AbbVie: Other: sponsored for educational meetings, Speakers Bureau; Janssen: Other: sponsored for educational meetings, Speakers Bureau; Gilead: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Wiestner:Pharmacyclics LLC, an AbbVie Company; Acerta, Merck, Nurix, Verastem, and Genmab: Research Funding; National Institutes of Health: Patents & Royalties: and other intellectual property. Broom:Gilead: Other: Travel support, Speakers Bureau. Kater:Abbvie: Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Genentech: Research Funding. Ujjani:AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Verastem Oncology: Consultancy, Honoraria; Gilead/Kite: Consultancy, Research Funding; Atara: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; MorphoSys: Consultancy. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Gilead: Other: travel grants, Research Funding; Abbvie: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Chong:Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; KITE Pharma: Membership on an entity's Board of Directors or advisory committees. Pu:Takeda Pharmaceuticals: Consultancy. Brown:Janssen, Teva: Speakers Bureau; Gilead, Loxo, Sun, Verastem: Research Funding; Abbvie, Acerta, AstraZeneca, Beigene, Invectys, Juno/Celgene, Kite, Morphosys, Novartis, Octapharma, Pharmacyclics, Sunesis, TG Therapeutics, Verastem: Consultancy. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Sanchez:Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Shadman:Abbvie, Genentech, Astra Zeneca, Sound Biologics , Pharmacyclics, Verastem, ADC therapeutics, Beigene, Cellectar, BMS, Morphosys and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Pharmacyclics, Gilead, Genentech, Abbvie, TG therapeutics, Beigene, Astra Zeneca, Sunesis, Beigene: Research Funding. Foglietta:Janssen: Honoraria; Gilead: Honoraria. Jaksic:Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Sportoletti:AbbVie: Honoraria; Janssen: Honoraria. Barr:Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Verastem: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy; Merck: Consultancy; Genentech: Consultancy; Janssen: Consultancy. Ruchlemer:Abbvie Inc: Consultancy, Research Funding. Kersting:Celgene: Other: travel grant; Janssen: Research Funding; Abbvie: Research Funding. Huntington:Pharmacyclics: Honoraria; AbbVie: Consultancy; Novartis: Consultancy; Genentech: Consultancy; DTRM: Research Funding; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; TG Therapeutics: Research Funding. Herishanu:Roche: Honoraria; Sanofi: Honoraria; Medison: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria. Jacobs:TG Therapeutics, Inc.: Research Funding; Astra Zeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; Seattle Genetics: Consultancy; Verastem: Consultancy; Janssen: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Sanofi Genzyme: Speakers Bureau. Portell:BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding; Bayer: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; AbbVie: Research Funding. Rambaldi:Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Astellas: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); University of Milan: Current Employment; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Received travel support., Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support from Gilead.; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Research grant from Amgen Inc.; Omeros: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Advisory board and speaker fees from Pfizer.. Brander:Verastem: Consultancy, Honoraria, Other, Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding. Rossi:Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Coscia:Karyopharm Therapeutics: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Coombs:Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; MEI Pharma: Honoraria; LOXO Oncology: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. Schuster:Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria. Foà:Abbvie: 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; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cuneo:Astra Zeneca: Honoraria; Gilead: 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; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bosch:Jansen: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Astra Zeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Roche: Honoraria. Stamatopoulos:AstraZeneca: Honoraria; Janssen, Gilead, Abbvie: Honoraria, Research Funding. Ghia:Adaptive, Dynamo: Consultancy, Honoraria; Novartis: Research Funding; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene/Juno: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; MEI: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Research Funding; ArQule: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria. Mato:Adaptive: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding.

Background:Transient osteoporosis (TOP) or transient bone marrow edema syndrome is an enigmatic condition of unknown etiology first described in pregnant women. Though usually self limited, TOP causes pain and debilitation and predisposes the patient to avascular necrosis or fractures. The course can be protracted and patient may suffer relapses. Diagnostic method of choice is magnetic resonance imaging (MRI). Based on small case series and expert opinion, several therapeutic approaches have been proposed to hasten the recovery, including bisphosphonates, calcitonin, teriparatide. However, the literature is scarce and additional experience is needed to promote the understanding of this condition.Objectives:To present our experience with TOP, including patient’s characteristic, approach to diagnosis, prognosis and therapyMethods:It is retrospective, single center study, conducted in Rambam healthcare campus, Haifa, Israel. All the medical files of patients referred to Rheumatology unit between years 2010-2020 were screened for diagnosis of TOP. Search words included: “osteoporosis”, “bone marrow edema”, “transient osteoporosis”. The files were reviewed for patient’s characteristics, modality of diagnosis, duration until full recovery, treatments and relapses.Results:Eight patients with at least one episode of TOP were identified using the search words. Six patients (75%) were female. Three female patients developed TOP during or shortly after pregnancy. Two patients – one male and one non pregnant female suffered from TOP after bariatric surgery. One pregnant woman had a strong family history of TOP. The most frequent involved site in order of frequency were: hip (4/8), ankle (3/8) and knee (2/8). Six patients presented with more than one simultaneous site of TOP (hips, knees and ankles). Blood count, liver and Kidney function tests, markers of bone resorption, rheumatoid factor, Anti cyclic citrullinated peptide, Antinuclear antibodies were negative in all of the patients. C-reactive protein was elevated in 4/8 patients, Erythrocyte sedimentation rate was elevated in 2/8 patients. All patients had vitamin D deficiency. The diagnosis was confirmed by MRI. All the patients were treated with vitamin D and intra-venous Pamidronate, one patient with addition of calcitonin and one patient with addition of intra venous Iloprost. Time to recovery ranged from 1.2 to 6 months. The time to recovery was the same in pregnancy related TOP. Recovery was confirmed with follow-up MRI in all the patients. Relapses occurred in 4/8 patients and only one them had pregnancy related TOP. All the patients were treated by multidisciplinary team, including orthopedic surgeon, physiotherapist and psychologist when needed.Conclusion:Our experience with TOP was enriched in patients presenting with more than one site of disease probably representing referral bias. Pregnancy related TOP was associated with lower risk of relapse. In terms of time to recovery there was no trend between pregnancy related and non related TOP or one site versus several sited TOP. None of the patients developed fracture, advocating in favor of adding bisphosphonates to therapy. Multidisciplinary approach is an essential part of TOP treatment strategy.Disclosure of Interests:Sami Giryes: None declared, Katya Dolnikov: None declared, Alexandra Balbir-Gurman Consultant of: Novartis, Daniela Militianu: None declared, Natalia Puchkov: None declared, Yolanda Braun-Moscovici: None declared

INTRODUCTION. Kinase inhibitors and glycoengineered monoclonal antibody, such as obinutuzumab (G), have significantly changed the treatment landscape of chronic lymphocytic leukemia (CLL). Both like the BTK inhibitor ibrutinib (IB) and obinutuzumab plus chlorambucil (G-CHL) are approved as first line therapy in CLL patients unfit for a fludarabine-base treatment. While IB has proved to be superior to bendamustine-rituximab in a phase 3 trial and an ongoing retrospective ERIC study, no head-to-head comparison has been done for IB vs G-CHL in a real-world evidence study. The aim of this study was to compared the clinical efficacy of the fixed duration G-CHL treatment vs continuous treatment with IB. METHODS. The inclusion criteria for this observational study were patients with a diagnosis of CLL, requiring treatment according to the iwCLL guideline (Hallek M, Blood 2018) and considered unfit for fludarabine-base therapy by the treating physician belonging to the Italian CLL campus. Patients received ibrutinib 420mg daily until progression or unacceptable toxicity, while G was administrated at 100mg on day 1, 900mg on day 2 and 1000mg on days 8 and 15 of the 1st cycle, then at 1000mg from cycles 2-6. Chlorambucil was administrated according to the local policy. An IGHV gene sequence homology ³98% was considered as unmutated (U-IGHV), as opposed to mutated (M-IGHV). TP53 disruptions (TP53dis) included deletions and mutations. Progression-free survival (PFS), time-to-next treatment (TTNT) and overall survival (OS) were calculated according to the iwCLL 2018 guideline. Minimal residual disease (MRD), assessed by flow cytometry, was considered undetectable when &lt;10-4 (uMRD4). Survival curves were compared with the log-rank test and p&lt;0.05 was considered as significant. The study was approved by the ethic committee of Padua university hospital. RESULTS. We recruited 284 CLL patients from 16 hematologic centers, 104 were treated with G-CHL and 180 with IB as first-line treatment. Once TP53dis cases were excluded, 102 patients treated with G-CHL and 80 treated with IB were included for further analysis. Among patients managed with G-CHL the median age was 75 years and 20% were older than 80 years, 47% had a CIRS≥6 (range 2-18), 68% had a clearance creatinine &lt;70ml/min, 60% showed a Rai stage III-IV, 32% were U-IGHV and 11% harbored 11q deletion by FISH. Patients treated with IB displayed a better renal function (p=0.0011) and were enriched in U-IGHV cases (p=0.0001). After a median follow-up of 21 months, 23 patients relapsed (20 G-CHL, 3 IB), 16 required a subsequent treatment (14 G-CHL, 2 IB) and 17 died (10 G-CHL and 7 IB). Two patients in the IB arm developed Richter syndrome. After 8 months from the start of treatment, the overall response rates in the G-CHL and IB arms were 86% vs 77% (p=0.1480), including 25% vs 6% complete remissions (CR, p=0.0013) and 61% vs 71% partial responses (PR, p=0.6320). Remarkably, an uMRD4 by flow-cytometry was documented in 42% and 9% of G-CHL patients in the peripheral blood and bone marrow, respectively. The median PFS was 33 months for G-CHL arm, but not reached for IB patients. The 24months PFS, TTNT and OS was 67% vs 91% (p=0.0012), 83% vs 97% (p=0.0128) and 89% vs 95% (p=0.5314) for the G-CHL and IB arms, respectively. Interestingly, the depth of response influenced PFS only in the G-CHL arm both in terms of clinical response (the median PFS was 8, 29 and 38 months for no responding, PR and CR patients) and MRD status (the 24 months PFS was 82% vs 50% and 100% vs 58% for uMRD4 vs MRD+ evaluated on peripheral blood and bone marrow). While the PFS was significantly better with IB than with G-CHL in U-IGHV (p=0.007), it was superimposable for M-IGHV patients (p=0.1946). Dose reductions or discontinuations were recorded in 39% and 44% of patients in the G-CHL and IB arms. Atrial fibrillation and infections occurred in 2% and 6% (p=0.0442), and in 25% and 17% (p=0.1455) of patients in the G-CHL and IB arms, respectively. CONCLUSIONS. The Italian experience with G-CHL confirms the marked efficacy and safety of this combination, in particular for patients who reach a CR and/or an uMRD4. The continuous treatment with ibrutinib provides a better disease management in CLL patients unfit for fludarabine-base therapy, but some on them - particularly those with a M-IGHV status - can achieve a long-term disease control with a fixed duration obinutuzumab-based chemoimmunotherapy. Disclosures Visentin: Janssen: Honoraria; Gilead: Honoraria; Abbvie: Honoraria. Mauro:Takeda: Membership on an entity's Board of Directors or advisory committees; Octopharma: Consultancy; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jannsen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vitale:Janssen: Honoraria. Ciolli:Janssen: Honoraria; Abbvie: Research Funding. Sportoletti:Janssen: 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, Speakers Bureau. Rigolin:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Murru:Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: 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, Speakers Bureau. Gozzetti:Janssen: Honoraria, Research Funding; Takeda: Honoraria; Amgen: Honoraria. Molica:Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: 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, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees. Marchetti:Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Scarfo:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria. Reda:Gilead: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Coscia:Karyopharm Therapeutics: Research Funding; Shire: 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; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Laurenti:Gilead: 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, Speakers Bureau; Janssen: 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. Pizzolo:Abbvie: Speakers Bureau; janssen: Speakers Bureau. Semenzato:Takeda: Honoraria; Roche: Honoraria; Abbvie: Honoraria. Foà:Novartis: Speakers Bureau; Abbvie: 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; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees. Cuneo:Gilead: 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, Speakers Bureau; janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Trentin:Shire: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.

Background:There is some evidence that neuropsychiatric changes occur in systemic lupus(1) and rheumatoid arthritis(2). However, little is known regarding a possible disease-related impairment of cognitive abilities in axial spondyloarthritis (axSpA).Objectives:To evaluate patients with axSpA regarding cognitive impairments.Methods:Patients with axSpA attending two rheumatology practices were routinely evaluated by rheumatologists and underwent a computer-based memory and attention test (MAT) (3, 4) with subscale scores ranging from 0 (worst) to 15 (best). The results of short-term memory and working memory were compared to an age-, sex- and education-matched control group of healthy subjects. Descriptive results are presented as median (IQR) for interval data and n (%) for nominal data if not stated otherwise. Two-tailed Wilcoxon signed-rank tests including Bonferroni-Holm adjustment for multiple tests were conducted to investigate the magnitude of potential differences in cognitive abilities.Results:101 consecutive patients were tested (Table 1). After multiple testing adjustment for two subscales, Wilcoxon signed-rank tests returned significant findings for working memory (V = 539.5, p = 0.006, |r| = 0.204) but not for short-term memory (V = 1075, p = 0.351, |r| = 0.078). Regarding the scales’ anchors, descriptive results on pairwise differences suggested axSpA patients to have working memory scores that are on average 10.7% lower compared to control participants (mean Δ= -1.64, SD Δ= 5.95).Table 1.Patients and disease characteristicsn%MeanSDMedian25% Quantile75% QuantileAge10110051.111.6524260Age (female)4847.552.611.75444.561Age (male)5352.549.811.5514157< 13 years formal education4746.5≥ 13 years formal education5453.5HLA B27 positive n/N64/9263.4Disease duration (years)10110013.711.712421Disease duration (female, years)4847.511.69.99417.2Disease duration (male, years)5352.515.512.915523BASDAI9291.13.71.73.82.45BASFI9190.132.42.31.24.5BASMI7574.31.92.3103ASDAS98972.30.82.31.82.8Conclusion:The MAT computerized testing is a feasible test and was well accepted by patients. Results regarding working memory suggest that cognitive abilities needed to accomplish everyday tasks may be impaired in axSpA patients. Further work is needed to characterise possible causes of or associations with this cognitive impairment.References:[1]Zabala A, Salgueiro M, Saez-Atxukarro O, Ballesteros J, Ruiz-Irastorza G, Segarra R. Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis. J Int Neuropsychol Soc. 2018:1-11.[2]Vitturi BK, Nascimento BAC, Alves BR, de Campos FSC, Torigoe DY. Cognitive impairment in patients with rheumatoid arthritis. J Clin Neurosci. 2019;69:81-7.[3]Adler G, Bektas M, Feger M, Lembach Y. [Computer-based assessment of memory and attention: evaluation of the memory and attention test (MAT)]. Psychiatr Prax. 2012;39(2):79-83.[4]Adler G, Lembach Y. Memory and selective attention in multiple sclerosis: cross-sectional computer-based assessment in a large outpatient sample. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):439-43.Acknowledgements:This study was funded by the RHADAR GbR (A Network of Rheumatologists), Bahnhofstr. 32, 82152 Planegg, Germany. RHADAR GbR has received a grant for this study from Novartis Pharma GmbH.Disclosure of Interests:Stefan Kleinert Consultant of: Novartis, Abbvie, Grant/research support from: Novartis, Praxedis Rapp: None declared., Florian Schuch Speakers bureau: Novartis, Abbvie, Gilead, Consultant of: Novartis, Abbvie, Gilead, Monika Ronneberger: None declared., Joerg Wendler Speakers bureau: Roche, Pharma, JanssenCilag, Novartis, Abbvie, Consultant of: JanssenCilag, Patrizia Sternad: None declared., Florian Popp: None declared., Peter Bartz-Bazzanella: None declared., Cay-Benedict von der Decken: None declared., Kirsten Karberg Speakers bureau: Roche, Sanofi, Abbvie, Lilly, Georg Gauler Speakers bureau: Abbvie, Gilead, Novartis, Lilly, Consultant of: Lilly, Gilead, Abbvie, Patrick Wurth Speakers bureau: Abbvie, Lilly, UCB, Medac, Susanna Spaethling-Mestekemper Speakers bureau: Abbvie, BMS, Celgene, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Christoph Kuhn: None declared., Matthias Englbrecht Speakers bureau: AbbVie, Chugai, Eli Lilly, Novartis, Roche, Sanofi, Mundipharma, Paid instructor for: AbbVie, Chugai, Roche, Consultant of: AbbVie, Novartis, Roche, Sanofi, Grant/research support from: Roche, Chugai, Wolfgang Vorbrüggen: None declared., Georg Adler: None declared., Martin Welcker Speakers bureau: Abbvie, Actelion, Amgen, Biogen,BMS, Berlin Chemie, Celgene, Galapagos, Gilead, GSK, Hexal, Janssen, Medac, MSD, Mundipharma, Mylan, Novartis, Pfizer, Roche, Sanofi, SOBI, UCB, Grant/research support from: Novartis, Abbvie.

Abstract Introduction. In the last few decades, the life expectancy of Thalassemia Major (TM) patients has progressively been increasing. The improvement can be due to several factors, including introduction of chelation treatment (Deferoxamine 1965, Deferiprone 1987, Deferasirox 2006), screening of blood for the most common viral agents, aggressive treatment of infection and improved treatment of cardiac complications. However, no comparative survival curves between TM versus Thalassemia Intermedia (TI) have been so far reported. Moreover, no data on life expectancy, after introduction of chelation treatment have been described. Methods. Data coming from several randomized clinical trials, carried ahead by Campus of Hematology Franco and Piera Cutino-A.O.O.R Villa Sofia-V. Cervello, Palermo (Italy), were retrospectively considered for this study. Primary goal of the study was to provide evidence of possible differences in survival curves between TM versus TI. Survival curves in TM versus TI patients were compared using Kaplan-Meier method and the log-rank test before and after the introduction of Deferoxamine (DFO) (1965). Moreover, Cox regression model was even used to explore risk of death between the two diagnoses. Each dead patient was observed from its birth to its death, and each alive patient was observed from its birth to June 30, 2015. Results. Three hundred seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) entered into the study. Males were 50.7% of this cohort of patients. Among the cohort of dead patients, 15% (6/40) TM and 76.9% (10/13) TI patients were born before introduction of DFO (1965) . The mean age survival was 50.6 (SE 0.9) and 70.6 (SE 1.7) for TM and TI, respectively. Table 1 shows the main causes of death. In TM patients the most common causes of death were heart damage (16 cases, 40%, Tab. 1), followed by cancer (3 cases, 7.5%, Tab. 1), liver cirrhosis (3 cases, 7.5%, Tab. 1) and infections (3 cases, 7.5%, Tab. 1). In TI patients the most common causes of death were cancer (2 cases, 38.5%, Tab. 1), followed by infections (3 cases, 23.1% , Tab. 1), heart damage (2 case, 15.4%, Tab. 1). Kaplan-Meir curves showed statistically significant difference in TM versus TI survival (log-rank test, p- value<0.0001; Figure 1A). Survival was higher for TI subjects (median age was 73.6 years). Cox regression models of TM versus TI suggested that risk of death for TM patients was 6.8 times higher than TI patients (HR 6.8 (3.3), p- value<0.0001). However, the introduction of chelation treatment (DFO, 1965), changed the Kaplan-Meier curves showing that there was not statistically significant difference between TM versus TI patients in life expectancy ( log-rank test, p- value=0.086; Fig. 1B). Conclusion. These results suggest as TM survival, after the introduction of chelation treatment, improved so much that nowadays it is not different in comparison with TI one's. Moreover, the TM risk of death has been decreased from 6.8 to 2.8 (Cox Model HR 2.8 (1.7), p- value=0.099). These findings, if further confirmed, suggest as, in Western countries, our approach for genetic counselling of "at risk couples" for TM should be reconsidered. Table 1. Causes of death in Thalassemia Major and Thalassemia Intermedia patients. Diagnosis Causes of Death TM n (%) TI n (%) Cancer 3 (7,5) 5 (38,5) Heart Damage 16 (40,0) 2 (15,4) Infection 3 (7,5) 3 (23,1) Multi Organ Failure 1 (2,5) 0 (0,0) Stroke 1 (2,5) 0 (0,0) Liver Failure 3 (7,5) 1 (7,7) Not Available 11 (27,5) 1 (7,7) Other complications not related to Thalassemia 2 (5,0) 1 (7,7) Total 13 40 Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.

Abstract Previous studies and meta-analyses addressing COVID-19 in patients with hematological malignancies (HM) have reported dramatically high mortality rates of up to 34% [Vigenthira 2020, Garcia-Suarez 2020, Sharafeldin 2021]. These studies, however, were strongly biased towards hospitalized patients, and poorly represented patients who experienced a milder course of COVID-19, not requiring hospitalization. Jerusalem and its metropolitan area, comprising of over 1.3 million inhabitants, was the epicenter of Israel's COVID-19 crisis, with over 200,000 cases. Hadassah Medical Center, one of only two tertiary centers serving this multi-ethnic population, houses a Hematology Department that includes inpatient services, a hematopoietic stem cell transplant (HSCT) center, day care services and in-campus outpatient clinics. From February 20 th, 2020, we tracked patients with confirmed COVID-19 reporting to their treating hematologists while being hospitalized due to COVID-19, at routine visits to the hematology services, or remotely via phone or email communication. This assured the representation of COVID-19 cases of various clinical severities. Data were collected retrospectively and included demographics, comorbidities, hematological diagnoses and treatments, course of COVID-19 and, importantly, source of infection. Univariate and multivariate analyses were used to assess association between prognostic factors and outcomes including hospitalization, severe COVID-19 (per updated WHO criteria) and critical COVID-19, defined as a composite of ICU admission and mortality. Almost all the patients in this series were diagnosed prior to their vaccination. To the best of our knowledge, this is the largest single center series of HM patients with COVID-19 reported to date. Our series included 183 patients. Median age was 62.5 years, 57% were men, and 72% had at least one comorbidity. The most frequent hematological diagnoses were indolent lymphoma and CLL (40%), aggressive lymphoma (20%) and multiple myeloma (19%). At the time of COVID-19 diagnosis, 41% of the patients were receiving systemic anti-neoplastic treatment (excluding TKIs for CML and hydroxyurea for MPN), and 16% had undergone a previous allogeneic or autologous HSCT. Overall mortality, severe COVID-19, and hospitalization rates in the entire group were 9.8%, 14.2% and 32%, respectively, remarkably lower than in previous reports. Of the patients not receiving anti-neoplastic treatment, mortality and severe COVID-19 rates were comparable to those of the age-matched general population according to the Israeli Ministry of Health database [Table 1]. Consistent with previous studies, ischemic heart disease (IHD), dyslipidemia, chronic kidney disease, smoking and hypertension, as well as age and active anti-neoplastic treatment, each emerged as a risk factor significantly associated with hospitalization due to COVID-19 [Fig. 1, Table 2]. IHD, smoking, age and active treatment remained significant in multivariate analysis. Age and active treatment as well as ≥4 comorbidities were significantly associated with critical COVID-19. Interestingly, we observed a strong association between the number of prior anti-neoplastic treatment lines and critical COVID-19. Neither history of HSCT nor treatment with monoclonal antibodies were associated with COVID-19 outcomes. Notably, we did not detect any patient that contracted COVID-19 within the Hematology Department services, both inpatient and outpatient. Taken together, we present a different COVID-19 severity landscape in patients with HM as compared to previous observations. While active treatment was significantly associated with COVID-19 hospitalization and mortality, these rates were remarkably lower than previously reported. Despite harboring various degrees of immune suppression, patients with stable or indolent diseases not receiving active treatment appeared to be at a risk comparable to that of the age-matched general population, which depended largely on age and comorbidities. Routine preventive measures including symptom questioning, masks, and social distancing in both our inpatient and outpatient services provided a COVID-19-safe environment, obviating the need for changes in treatment schedules or assignment. These findings may have important consequences for future management of patients with HM in COVID-19 affected regions. Figure 1 Figure 1. Disclosures Lavie: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Fees for lectures; Roche: Other: Fees for lectures; Novartis: Other: Fees for lectures; Takeda: Consultancy. Goldschmidt: AbbVie: Consultancy, Research Funding.

Background:Filgotinib (FIL) is an oral, potent, selective JAK1 inhibitor. FINCH 1 (NCT02889796) assessed FIL efficacy and safety in patients (pts) with rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX-IR); primary outcome results at week (W)12 and W24 were previously reported.1Objectives:To present FINCH 1 W52 results.Methods:This global, phase 3, double-blind, active- and placebo (PBO)-controlled study randomised MTX-IR pts with active RA on a background of stable MTX 3:3:2:3 to oral FIL 200 mg or FIL 100 mg once daily, subcutaneous adalimumab (ADA) 40 mg every 2W, or PBO up to W52; pts receiving PBO at W24 were rerandomised to FIL 100 or 200 mg. Efficacy was assessed from clinical, radiographic, and pt-reported outcomes; W52 comparisons were not adjusted for multiplicity. Safety endpoints included adverse events (AEs) and laboratory abnormalities.Results:Of 1755 treated pts, 1417 received study drug through W52. The majority (81.8%) were female, mean (standard deviation [SD]) RA duration was 7.8 (7.6) years, and baseline mean (SD) DAS28(CRP) was 5.7 (0.9). FIL efficacy was sustained through W52; 54%, 43%, and 46% of pts receiving FIL 200 and 100 mg and ADA, respectively, had W52 DAS28(CRP) <2.6 (nominal p for FIL 200 vs ADA = 0.024) (Figures 1–2, Table 1). FIL safety profile through W52 was consistent with W24 data. AEs of interest were infrequent and balanced among treatments (Table 2); 82 pts (4.7%) discontinued treatment due to AEs.Table 1.Efficacy outcomes at week 52FIL 200 mg(n = 475)FIL 100 mg(n = 480)ADA(n = 325)ACR20/50/70, %78/62/4476/59/3874/59/39DAS28(CRP) ≤3.2, %66+5959mTSSa0.18+++0.450.61HAQ-DIb−0.93+−0.85−0.85SF-36 PCSb12.011.512.4FACIT-Fb11.912.211.7aLeast squares mean change from baseline.bMean change from baseline.+p <0.05,+++p <0.001 vs ADA; not adjusted for multiplicity.ADA, adalimumab; FIL, filgotinib; mTSS, modified van der Heijde TSS.Table 2.Treatment-emergent AEs through week 52Event, n (%)FIL 200(n = 475)FIL 100 mg(n = 480)ADA(n = 325)All AEs352 (74.1)350 (72.9)239 (73.5)Serious AEs35 (7.4)40 (8.3)22 (6.8)Infection206 (43.4)194 (40.4)129 (39.7)Serious infection13 (2.7)13 (2.7)10 (3.1)Herpes zoster6 (1.3)4 (0.8)2 (0.6)VTE1 (0.2)01 (0.3)MACE (adjudicated)02 (0.4)1 (0.3)Malignancy (excluding NMSC)2 (0.4)2 (0.4)2 (0.6)NMSC1 (0.2)1 (0.2)0Death3 (0.6)1 (0.2)1 (0.3)Data omitted for patients rerandomised from placebo to FIL.ADA, adalimumab; AE, adverse event; FIL, filgotinib; MACE, major adverse cardiovascular event; NMSC, nonmelanoma skin cancer; VTE, venous thromboembolism.Conclusion:Through W52, both FIL 200 and 100 mg showed sustained efficacy based on clinical and pt-reported outcomes and radiographic progression and were well tolerated in MTX-IR pts with RA, with faster onset and numerically greater efficacy for FIL 200 vs 100 mg.References:[1]Combe et al.,Ann Rheum Dis.2019; 78 (Suppl 2):77–8.Disclosure of Interests:Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, J-Abraham Simon-Campos: None declared, Herbert S.B. Baraf Grant/research support from: Horizon; Gilead Sciences, Inc.; Pfizer; Janssen; AbbVie, Consultant of: Horizon; Gilead Sciences, Inc.; Merck; AbbVie, Speakers bureau: Horizon, Uma Kumar: None declared, Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Lei Ye Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Chantal Tasset Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, John Sundy Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Angelika Jahreis Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Neelufar Mozaffarian Shareholder of: Gilead, Employee of: Gilead, Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Sang-Cheol Bae: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB, Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB

BackgroundToday, there are still no DMARDs licensed for primary Sjögren Syndrome (pSS) patients. Among the explanations, are the limitations of current outcome measures used as primary endpoints: e.g; high placebo response rate, evaluation of either symptoms or systemic activity, and important features not being assessed. The NECESSITY consortium (https://www.necessity-h2020.eu/), including pSS experts from academia, pharmaceutical industry and patient groups formed to develop a new composite responder index, the Sjögren’s Tool for Assessing Response (STAR) that solve the issues of current outcome measures in pSS and is intended for use in clinical trials as an efficacy endpoint.ObjectivesTo develop a composite responder index in primary Sjögren’s syndrome (pSS): the STAR.MethodsTo develop the STAR, the NECESSITY consortium used data-driven methods, based on 9 randomized controlled trials (RCTs), and consensus techniques, involving 78 experts and 20 patients. Based on reanalysis of rituximab trials (TRACTISS and TEARS) and literature review, the Delphi panel identified a core set of domains to include in the STAR, with their respective outcome measures. STAR options combining these domains were designed and proposed to the panel to select and improve them. For each STAR option, sensitivity to change was estimated by the C-index (derived from Effect size) in all 9 RCTs. Delphi rounds were run for selecting STAR among these options. The Delphi panel also voted to classify trials as positive, negative or “in between” in regards to primary but also key secondary endpoints. For the options remaining before the final vote, meta-analyses of the RCTs were performed separately for positive and “in between” trials together, and for negative trials.ResultsThe Delphi panel identified 5 core domains (systemic activity, patient symptoms, lachrymal gland function, salivary gland function and biological parameters), and 227 STAR options, combining these domains, were selected to be tested for sensitivity to change. After two Delphi rounds, meta-analyses of the 20 remaining options were performed. The candidate STAR was selected by a final vote based on metrological properties and clinical relevance. In positive/in between trials, candidate STAR detected a difference between arms (OR 3.29, 95%-CI [2.07;5.22], whereas it did not in negative trials (OR 1.53, 95%-CI [0.81;2.91]).ConclusionThe candidate STAR is a composite responder index, including in a single tool all main disease features, and is designed for use as a primary endpoint in pSS RCTs. Its rigorous and consensual development process ensures its face and content validity. The candidate STAR showed good sensitivity and specificity to change. The candidate STAR will be prospectively validated in a dedicated three arms RCT of the NECESSITY consortium that will evaluate combination of synthetic DMARDs (hydroxychloroquine + lefunomide or hydroxychloroquine + mycophenolate vs placebo). We encourage the use of STAR in any ongoing and future trials.Table 1.Candidate STARDomainPointDefinition of responseSystemic activity3Decrease of clinESSDAI ≥ 3Patient reported outcome3Decrease of ESSPRI ≥ 1 point or ≥ 15%Lachrymal gland function1Schirmer:If abnormal score at baseline: increase ≥ 5 mm from baselineIf normal score at baseline: no change to abnormalOrOcular Staining Score:If abnormal score at baseline: decrease ≥ 2 points from baselineIf normal score at baseline: no change to abnormalSalivary gland function1Unstimulated Whole Salivary Flow:If score > 0 at baseline: increase ≥ 25% from baselineIf score is 0 at baseline: any increase from baselineorUltrasound:Decrease ≥ 25% in total Hocevar score from baselineBiological1Serum IgG levels: decrease ≥ 10%orRheumatoid Factor levels: decrease ≥ 25%Candidate STAR responder≥ 5 pointsESSDAI: EULAR Sjögren syndrome disease activity index; ESSPRI: EULAR Sjögren syndrome patient reported index; IgG: Immunoglobulin G;AcknowledgementsNECESSITY WP5 STAR development participants: Suzanne Arends (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Francesca Barone (Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK), Albin Björk (Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden), Coralie Bouillot (Association Française du Gougerot Sjögren et des Syndromes Secs, France), Guillermo Carvajal Alegria (University of Brest, Inserm, CHU de Brest, LBAI, UMR1227, Brest, France; Service de Rhumatologie, Centre de Référence Maladies Autoimmunes Rares CERAINO, CHU Cavale Blanche, Brest, France), Wen-Hung Chen (GlaxoSmithKline, Research Triangle Park, North Carolina, USA), Kenneth Clark (GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom), Konstantina Delli (Department of Oral and Maxillofacial Surgery, University Medical Center Groningen (UMCG), University of Groningen, The Netherlands), Salvatore de Vita (Rheumatology Clinic, University Hospital of Udine, Italy), Liseth de Wolff (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Jennifer Evans (Novartis Pharmaceuticals corporation USA), Stéphanie Galtier (Institut de Recherches Internationales Servier (IRIS), Suresnes Cedex, France), Saviana Gandolfo (Rheumatology Clinic, Department of Medical area, University of Udine, ASUFC, 33100 Udine, Italy), Mickael Guedj (Institut de Recherches Internationales Servier (IRIS), Suresnes Cedex, France), Dewi Guellec (CHU de Brest, Service de Rhumatologie, Inserm, CIC 1412, Brest, France), Safae Hamkour (Center of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht 3584 GA, Netherlands), Dominik Hartl (Novartis Institutes for BioMedical Research, Basel, Switzerland), Malin Jonsson (Section for Oral and Maxillofacial Radiology, Department of Clinical Dentistry, Faculty of Medicine and Dentistry, University of Bergen, Norway), Roland Jonsson (Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Department of Rheumatology, Haukeland University Hospital, Bergen, Norway), Frans Kroese (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Aike Albert Kruize (University Medical Center Utrecht, Department Rheumatology and Clinical Immunology, Utrecht, Netherlands), Laurence Laigle (Institut de Recherches Internationales Servier (IRIS), Suresnes Cedex, France), Véronique Le Guern (AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, service de médecine interne, Paris, France), Wen-Lin Luo (Department of Biometrics and Statistical Science, Novartis Pharmaceuticals, East Hanover, New Jersey), Esther Mossel (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Wan-Fai Ng (Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK), Gaëtane Nocturne (Department of Rheumatology, Université Paris-Saclay, INSERM U1184: Centre for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, Paris, France), Marleen Nys (Global Biometric Sciences, Bristol Myers Squibb, Braine L’Alleud, Belgium), Roald Omdal (Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, PO Box 8100, 4068, Stavanger, Norway), Jacques-Olivier Pers (LBAI, UMR1227, University of Brest, Inserm, Brest, France and CHU de Brest, Brest, France), Maggy Pincemin (Association Française du Gougerot Sjögren et des Syndromes Secs, France), Manel Ramos-Casals (Department of Autoimmune Diseases, Hospital Clinic de Barcelona Institut Clinic de Medicinai Dermatologia, Barcelona, Catalunya, Spain), Philippe Ravaud (Centre d’Epidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, Paris, France), Neelanjana Ray (Global Drug Development - Immunology, Bristol Myers Squibb Company, Princeton, New Jersey, USA), Alain Saraux (HU de Brest, Service de Rhumatologie, Univ Brest, Inserm, UMR1227, Lymphocytes B et Autoimmunité, Univ Brest, Inserm, LabEx IGO, Brest, France), Athanasios Tzioufas (Rheumatology Clinic, Department of Medical area, University of Udine, ASUFC, 33100 Udine, Italy), Gwenny Verstappen (University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen 9700 RB, Netherlands), Arjan Vissink, Marie Wahren-Herlenius (Division of Rheumatology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden). We thank the following experts: Esen Karamursel Akpek, Alan Baer, Chiara Baldini, Elena Bartoloni, Marí-Alfonso Begona, Johan Brun, Vatinee Bunya, Laurent Chiche, Troy Daniels, Paul Emery, Robert Fox, Roberto Giacomelli, John Gonzales, John Greenspan, Robert Moots, Susumu Nishiyama, Elizabeth Price, Christophe Richez, Caroline Shiboski, Roser Solans Laque, Muthiah Srinivasan, Peter Olsson, Tsutomu Takeuchi, Frederick Vivino, Paraskevi Voulgari, Daniel Wallace, Ava Wu, Wen Zhang. We thank the anonymous patients from the NECESSITY Patient Advisory Group and the Sjögren Foundation for their valuable contribution to the Delphi process. We thank EW StClair and AN Baer who generated the baminercept data and made them publicly available.Disclosure of InterestsRaphaèle Seror Consultant of: GlaxoSmithKline, Boehringer, Janssen and Novartis, Grant/research support from: GlaxoSmithKline and Amgen, Gabriel Baron: None declared, Marine Camus: None declared, Divi Cornec Consultant of: GlaxoSmithKline, Bristol Myers Squibb, Janssen, Amgen, Pfizer and Roche, Elodie Perrodeau: None declared, Simon J. Bowman Consultant of: Abbvie, Astra Zeneca, Galapagos and Novartis Pharmaceuticals, Michele Bombardieri Consultant of: UCB, Amgen/Medimmune, Janssen, and GlaxoSmithKline, Grant/research support from: Amgen/Medimmune, Janssen, and GlaxoSmithKline, Hendrika Bootsma: None declared, Jacques-Eric Gottenberg Consultant of: AbbVie, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Pfizer, Roche, Sanofi, Novartis, MSD, CSL-Behring and Genzyme, Grant/research support from: Bristol Myers Squibb, Benjamin Fisher Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Novartis, Bristol Myers Squibb, Janssen and Servier, Grant/research support from: Servier, Galapagos and Janssen, Wolfgang Hueber Shareholder of: Novartis Pharma, Employee of: Novartis Pharma, Joel van Roon: None declared, Valerie Devauchelle-Pensec: None declared, Peter Gergely Shareholder of: Novartis Pharma, Employee of: Novartis Pharma, Xavier Mariette Consultant of: Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Ose Pharmaceuticals, Raphaël Porcher: None declared

BackgroundPeresolimab is a humanized immunoglobulin G1 monoclonal antibody that stimulates human programmed cell death protein 1 (PD-1). We hypothesized that peresolimab binding to PD-1, a checkpoint inhibitory receptor, could stimulate physiological immune inhibitory pathways to restore immune homeostasis; this represents a novel approach to treating patients with autoimmune or autoinflammatory diseases.ObjectivesThe objective of this study was to evaluate efficacy and safety of peresolimab in adult participants with moderate-to-severe rheumatoid arthritis (RA).MethodsA Phase 2a, placebo-controlled, double-blind, randomized clinical trial (NCT04634253) evaluated the efficacy and safety of peresolimab in adult participants with moderately to severely active RA, who had an inadequate response to prior disease modifying drugs, either conventional (csDMARDs), biologic (bDMARDs) or synthetic (tsDMARDS).Treatment comparisons versus placebo were made using mixed effects model for repeated measures (MMRM) and using logistic regression model for continuous and binary endpoints, respectively. Nominal p-values are reported. Missing data for binary endpoints were imputed as non-response.ResultsOne hundred and one patients were randomly assigned 2:1:1 to receive intravenous peresolimab 700 mg (n = 49), 300 mg (n = 25), or placebo (n = 24) Q4W; 98 participants received at least one dose of study treatment and were included in the analysis.Baseline demographics and disease activity were similar among groups. The majority (83.7%) of participants were female. At baseline, the mean (SD) duration of RA was 10.0 (8.0) years, and the mean (SD) DAS28-CRP score was 5.9 (0.85).This trial met its primary endpoint of a significantly greater improvement from baseline at Week 12 in DAS28-CRP score in participants treated with peresolimab vs participants treated with placebo at both tested doses (700 mg [p < 0.001] and 300 mg [p = 0.017], figure 1a).Significant improvements were seen in CDAI between participants treated with either peresolimab dose (figure 1b) relative to placebo, and for ACR20 (p < 0.05) for participants treated with peresolimab 700 mg relative to placebo by Week 12 (table 1).Peresolimab exhibited a safety and tolerability profile that supports further clinical evaluation in immunologic disease.ConclusionPeresolimab, a PD-1 receptor agonist, was superior to placebo at Week 12 for several key endpoints in RA. Safety events were similar between treatment groups.Table 1.Primary and Secondary Efficacy Outcomes at Week 12†Placebo (N=24)Peresolimab 300mg (N=25)Peresolimab 700mg (N=49)Primary endpointDAS28-CRP CFB LSM (SE)-0.99 (0.261)-1.88 (0.249)*-2.09 (0.184)***Secondary endpointsACR20 – n (%)10 (41.7)11 (44.0)35 (71.4)*ACR50 – n (%)5 (20.8)5 (20.0)19 (38.8)ACR70 – n (%)4 (16.7)1 (4.0)10 (20.4)TJC68 CFB LSM (SE)-6.89 (1.846)-12.08 (1.814)*-12.33 (1.288)*SJC66 CFB LSM (SE)-6.18 (1.091)-10.22 (1.082)*-10.49 (0.759)**PGA (VAS) CFB LSM (SE)-25.35 (5.162)-39.07 (5.130)-38.55 (3.576)*PatGA (VAS) CFB LSM (SE)-21.66 (5.390)-24.27 (5.285)-29.67 (3.741)Arthritis Pain (VAS) CFB LSM (SE)-17.94 (5.101)-23.50 (5.000)-31.55 (3.535)*HAQ-DI CFB LSM (SE)-0.41 (0.109)-0.35 (0.107)-0.42 (0.076)hsCRP CFB LSM (SE)1.34 (3.717)-5.26 (3.626)-0.66 (2.574)CDAI CFB LSM (SE)-13.75 (2.709)-24.06 (2.628)**-25.51 (1.854)***SDAI CFB LSM (SE)-13.80 (2.664)-25.06 (2.571)**-26.90 (1.880)***DAS28-CRP = disease activity score-28 for RA with C-reactive protein. ACR = American college of rheumatology. CFB = change from baseline. TJC68 = tender joint count of 68 joints. SJC66 = swollen joint count of 66 joints. VAS = visual analogue scale. PGA = physician’s global assessment of disease activity. PatGA = patient’s global assessment of disease activity. HAQ-DI = health assessment questionnaire – disability index. hsCRP = high sensitivity C-reactive protein. CDAI = clinical disease activity index. SDAI = simplified disease activity index. †Least squares mean (SE) are reported, unless otherwise stated. *p value < 0.05. **p value < 0.01. ***p value < 0.001.AcknowledgementsWe would like to thank the patients and investigators who participated in the trial. Eli Lilly and Company or its representatives provided data, laboratory, and site monitoring services. Writing assistance was provided by Conor McVeigh, PhD. This work has been presented previously at the following scientific conference: ACR 2022, 14th of November 2022.Funding sourcesThis study was sponsored by Eli Lilly and Company.Disclosure of InterestsJay Tuttle Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Edit Drescher: None declared, Jesús Abraham Simon-Campos: None declared, Paul Emery Paid instructor for: Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Galapaos, Gilead, Eli Lilly and Company, Novartis, Pfizer, Roche, and Samsung, Consultant of: Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Eli Lilly and Company, Grant/research support from: Abbvie, BMS, Eli Lilly and Company, Novartis, and Samsung, Maria Greenwald Consultant of: Eli Lilly and Company, Alan Kivitz Shareholder of: Pfizer, Sanofi S.A, GSK, Gilead, Novartis, and Amgen, Paid instructor for: Celgene, Merck, Eli Lilly and Company, Novartis, Pfizer, Sanofi S.A, Sanofi Genzyme, Flexion therapeutics, Abbvie, Amgen, Genentech, UCB, Horizon, and GSK, Consultant of: Pfizer, Janssen Pharmaceuticals, Boehringer Ingelheim, Abbvie, Flexion Therapeutics, Gilead, Sanofi A.A, Regeneron, Sun Pharma Advanced Research, and ECOR1, Hyungmin Rha Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Pia Yachi Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Christina Kiley Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ajay Nirula Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company.

BackgroundThe SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare disease (<1/10,000) with multiple cutaneous and musculoskeletal manifestations [1]. The most common dermatological manifestations are palmoplantar pustulosis (PPP) and severe acne (SA). Musculoskeletal manifestations are diverse, including the thoracic wall, spine, temporomandibular joint, and peripheral joints [2]. It is considered as part of spondyloarthropathies, however, no significant relationship with HLA-B27 has been found [3]. For treatment, non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying drugs (DMARDs) and bisphosphonates have been traditionally used. More recently, new therapies such as apremilast and biological DMARDs (4) are being used more frequently.ObjectivesTo examine the characteristics of individuals diagnosed with SAPHO syndrome during follow-up at multiple Rheumatology Services in Spain.MethodsThis is a descriptive, cross-sectional, multi-center study, carried out in the Rheumatology Services of several hospitals in Spain. A convenience sampling was carried out, including all patients with SAPHO under active follow-up.Results50 patients were included (76% women), with a mean age of 48.56 (±12,28) years. The mean BMI was 24.84 (±4.31). Regarding cardiovascular risk factors, 36.2% and 23.4% were smokers and ex-smokers, respectively. 18% had hypertension, 28% had dyslipidaemia and 8% were diabetic.Regarding of the musculoskeletal involvement, the most affected region was the anterior chest wall (74%), followed by peripheral arthritis (56%) and the spine (34%). 24% presented enthesitis and only 6% dactylitis. The most frecuent skin involvement was palmpplantar pustulosis in 54% (27), the distribution of dermatological manifestations is shown in Figure 1.Figure 1.Skin manifestations in SAPHO syndrome.In laboratory tests at diagnosis, acute phase reactants were slightly elevated, with a mean of CRP of 11.13 (±17.34) and ESR of 21.21 (±24.56). HLA-B27 and CW6 were positive in 12% (6) and 6% (3) of patients, respectively. The most commonly used imaging tests in the diagnosis and follow-up were plain x-rays (90%), MRI (76%), bone scintigraphy (72%), and CT scan (52%). The least used test was ultrasound, used in 17 patients (34%).The treatment was mostly based in NSAIDs, 94% of patients received it at some point. 60% used DMARDsc (mostly methotrexate). 50% of patients received bDMARDs, and 9 patients received more than two bDMARDs throughout the follow-up. The distribution of the first bDMARD used is shown in Table 1.Table 1.First bDMARD used in the treatment of SAPHO syndrome in our cohort.bDMARDN% patients (25/50)% FAMEb/other molec’s (25/25)Adalimumab122448Infliximab4816Etanercept3612Ustekinumab248Secukinumab124Anakinra124Apremilast124Cartolizumab-pegol124Total2550100The course of the disease was mostly recurrent (54%) with asymptomatic periods between flare-ups. About half of the patients (44%) in follow-up currently have active disease.ConclusionOur cohort presented axial involvement like other series and significant peripheral involvement. The most frequent skin condition was PPP. Half of the patients in our cohort required bDMARD, with ADL being the most widely used.References[1]Heldmann F, Kiltz U, Baraliakos X, Braun J. [SAPHO syndrome]. Z Rheumatol. Octubre de 2014;73(8):729-41.[2]Hayem G, Bouchaud-Chabot A, Benali K, Roux S, Palazzo E, Silbermann-Hoffman O, et al. SAPHO syndrome: a long-term follow-up study of 120 cases. Semin Arthritis Rheum. diciembre de 1999;29(3):159-71.[3]Colina M, Govoni M, Orzincolo C, Trotta F. Clinical and radiologic evolution of synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: A single center study of a cohort of 71 subjects. Arthritis Care Res. 2009;61(6):813-21.[4]Daoussis D, Konstantopoulou G, Kraniotis P, Sakkas L, Liossis S-N. Biologics in SAPHO syndrome: A systematic review. Semin Arthritis Rheum. febrero de 2019;48(4):618-25.AcknowledgementsTo the Sociedad de Reumatología de la Comunidad de Madrid (SORCOM).Disclosure of InterestsBoris Anthony Blanco Cáceres Speakers bureau: MSD, Janssen, Novartis, UCB, Grant/research support from: Gebro, Pfizer, Novartis, Janssen, MSD, África Andreu-Suárez: None declared, Marta Valero: None declared, Diego Benavent: None declared, María Sanz: None declared, José Campos Esteban: None declared, Olga Rusinovich: None declared, Juan Molina Collada: None declared, patricia Castro: None declared, Vega Jovani: None declared, María Jesús Montesa: None declared, Eva Tomero Muriel: None declared, Álvaro García Martos: None declared, RAQUEL ALMODOVAR: None declared, Fernando Lozano Morillo: None declared.

Background:Objectives:Analyse the effect of secukinumab in terms of the patient´s own variables, specifically: fatigue, sleep, pain and quality of life in patients with psoriatic arthritis or spondyloarthritis.Methods:A multicentric longtitudinal observational prospective study was carried out at 6 months in patients who begin treatment with secukinumab. At the start and after 6 months the following data was collected on the outcome: pain through an visual analogue scale (VAS), fatigue using the FACIT-fatigue scale, sleeping problems using the insomnia severity index (ISI) and quality of life with the EuroQol-3L-5D and the PsAQoL.The sample can be described in terms of the distribution of the variables through measures of central tendency.It was analysed if the change after 6 months was statistically relevant using Student´s t-test for paired data in the case of FACIT, VAS, PsAQoL and ISI and chi-squared for the dimensions of the EQ-5D. The size of the effect of each of the measurements taken was calculated using Cohen’s D. the results are given grouped by disease and globally. The analysis was carried out using Stata v12 (College Station Tx, USA)Results:In table 1, the changes in the scales of normal distribution can be seen. Apart from general VAS, all the scales experience significant relevant changes. The PROs preferred by the patient with the best therapeutic response is the quality of sleep. The adjustment of the regression models does not produce changes in the results, apart from small adjustments to the condidence intervals (final column table 1). The subdomain in which the most significant change in the EQ-5D is produced is in that of pain and discomfort.Conclusion:After 6 months patients who begin treatment with secukinumab, present with improvements in all sizes of the effects of the treatment in the various studied scales. The improvement achieves global and generalised statistical significance after 6 months of study. The greatest effect is on sleep, quality of life and fatigue.The measurements of the outcomes reported by the patients are a clinical value added to our objective evaluations of the health and activity of the disease, and allow us, in a more integrated and comprehensive manner, to undertake a more exact and close evaluation of their state of health and wellbeing.Disclosure of Interests:JUAN JOSE LERMA: None declared, Antonio Gracia: None declared, Antonio Perez: None declared, Amalia Rueda: None declared, Clara Molina: None declared, M. Dolores Pastor: None declared, Isabel Balaguer Trull: None declared, Inmaculada Valiente: None declared, Cristina Campos Fernández: None declared, Javier Calvo: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

BackgroundDiagnosing early spondyloarthritis (SpA) is crucial for effective therapeutic intervention. Magnetic resonance imaging (MRI) helps us to diagnose non-radiographic SpA (nr-ax SpA) in an early stage according to the criteria of the imaging arm of the Assessment of Spondyloarthritis International Society (ASAS) classification. Diagnosis of sacroiliitis using MRI has limitations because of the lack of specificity and sensitivity. Several differential diagnoses are well known and should be considered1. In our daily practice, anomalies of the lower lumbar spine and the sacrum, such as spondylolysis, dysraphia, or assimilation joints, are often found to be accompanied by changes in the sacroiliac joints (SIG) corresponding to sacroiliitis.ObjectivesTo investigate the presence of anatomical anomalies of the lower lumbar spine in our cohort of early diagnosed nr-ax SpA patients fulfilling the criteria of ax SpA and show if they cause a difference in the outcome.MethodsPatients (n = 56, age < 45 years, symptom duration 3– 24 months) recently diagnosed with sacroiliitis using MRI and meeting the ASAS criteria for axial SpA were followed-up for 2 years2. We retrospectively analyzed the anatomic anomalies of the lower lumbar spine on MRI and, if available, on radiograph images.ResultsMRI on t0 revealed that 15 (26.7%, one female and 14 males) of 56 patients had anatomical anomalies of the lower lumbar spine, indicating bone marrow edema with clinical ax SpA according to the ASAS classification criteria. Spondylolysis, assimilation joints, and dysraphia were found in 4 (7.1%), 7 (12,5%), and 7 (12.5%) patients, respectively. The presence of HLA-B-27 and assessment results (CRP-ASDAS and BASDAI, BASMI) were similar to patients without the mentioned anatomical anomalies. Patients with spondylolysis and dysraphia of the lower spine and those without anomalies displayed similar progression of MRI findings between t0 and t2.ConclusionIn addition to the well-known noninflammatory causes of sacroiliitis, such as pregnancies or intensive sporting activity, anatomical peculiarities could not be considered noninflammatory reasons. Contrary to the latest literature3, they are not responsible for non-specific sacroiliitis. No difference in the development to axial SpA was observed when patients with and without anatomical changes were compared.References[1]de Winter J, de Hooge M, van de Sande M, et al. Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain. Arthritis Rheumatol. 2018 Jul;70(7):1042-1048.[2]SpA.47 (DGRH Congress 2021 virtuell Posterwalk) Is the course of newly diagnosed axial spondyloarthritis more aggressive than previously thought? Becker-Capeller,D et al.[3]Campos-Correia, D., Sudoł-Szopińska, I., & Diana Afonso, P. Are we overcalling sacroiliitis on MRI? Differential diagnosis that every rheumatologist should know - Part I. Acta reumatologica portuguesa 2019, 44(1), 29–41.Disclosure of InterestsDetlef Becker-Capeller Grant/research support from: Research support by Novartis, Smaragda Kapsimalakou: None declared

Introduction: Primary mediastinal B cell lymphoma (PMBL) is clinically and biologically distinct from the other subtypes of diffuse large B cell lymphoma (DLBCL), typically affecting young female patients (pts) with a bulky mediastinal mass. Standard treatment (TRT) is a combination of anti-CD20 antibody (Ab) and anthracycline-based chemotherapy. We aimed to compare patients' outcomes after CHOP delivered every 21 days (CHOP21) or 14 days (CHOP14) or ACVBP combined with anti-CD20 Ab in real life. Methods: All Pts treated in LYSA centers were eligible in this retrospective analysis. Inclusion criteria were as follow: age ≥18 years (yrs), newly diagnosed PMBL, TRT with CHOP or ACVBP plus anti-CD20 Ab between 2006 and 2017, and patient non-opposition statement. Primary endpoint was progression-free survival (PFS), secondary endpoints were: overall survival (OS), response rate (Lugano 2014) and total metabolic tumor volume (TMTV). Results: 313 pts were enrolled from 25 LYSA centers in France and Belgium. In all, median age at diagnosis was 32 (18-88) yrs. Majority of pts were female pts (60.7%) and presented at diagnosis with a good performance status (0-1: 81.8%), stage I-II (57.5%), elevated LDH (85%), Bulk&gt;10cm (58.5%) and low/low-intermediate aaIPI 0-1 (56.7%). Pts in the CHOP21 (n=57) group were older (median 40 yrs, vs 33 vs 29.5, p&lt;0.001), had more frequent low/low-intermediate risk aaIPI (71.4%, vs 55.6% vs 52.5%, p=0.044) and displayed a lower proportion of elevated LDH (66.7%, vs 88.2% vs 83.9%, p=0.014) as compared to CHOP14 (n=76) and ACVBP (n=180), plus anti CD20 Ab (Rituximab: n=296, obinutuzumab: n=17). 229 pts (73.2%) received intrathecal prophylaxis. Median number of chemotherapy cycles for CHOP21, CHOP14 and ACVBP groups were: 6 (1-8), 7.5 (1-8) and 4 (1-4), respectively. Consolidation ASCT was performed for 1 (1.8%), 24 (31.6%) and 46 (25.6%) pts, (p&lt;0.001) and mediastinal RT was delivered to 2 (3.5%), 11 (14.5%) and 4 (2.2%) pts, respectively (p&lt;0.001). ASCT + RT was done for 0, 5 (6.6%) and 3 (1.7%) pts, respectively (p=0.043). Baseline TMTV assessment was available for 233 pts (74.4%). Complete metabolic response rates at end of TRT were comparable between CHOP21, CHOP14 and ACVBP groups: 81.1%, 90.9%, and 85.5%, respectively (p=0.46). 37 (11.8%) pts progressed including 32 (10.2%) who displayed primary refractory disease and 6 (16.2%) pts who relapsed after consolidation ASCT. CNS relapse occurred in 9 (2.9%) pts. Median time between ASCT and relapse was 3 (2-58) months. Patients received the following salvage TRTs: high dose chemotherapy (HDC: R-ICE/R-DHAOX-like) (n=30) followed by second-line consolidation ASCT (n=11/30) and post-ASCT mediastinal RT (n=5/11); salvage RT without chemotherapy (n=1); other regimens (R-CHOP, R-GEMOX) (n=3); none (n=3). 2-yrs second PFS (PFS2) rates in pts who had previously received CHOP21, CHOP14 and ACVBP were: 20.5% vs 62.5% vs 18.8% (p=0.43). Only HDC + ASCT strategy granted disease control (2-yrs PFS2: 32.3%). Median follow up was 44 (1-153) months and the CHOP21, CHOP14, ACVBP 5-yrs PFS and 5-yrs OS were: 74.7% (95%CI: 64-97.1%), 89.4% (82.7-96.6%), 89.4% (84.8-94.2%) (p=0.018, Figure A); and 81% (70-94.4%), 100% (100-100%), 92.4% (88.4-96.7%) (p=0.0036, Figure B), respectively. In a multivariate model including TRT group, consolidation ASCT and/or RT, aaIPI, Bulk&gt;10cm and TMTV≥360cm3, CHOP14 was not associated with better PFS as compared to ACVBP and CHOP21 (p=0.1548). Baseline higher TMTV (≥ 360 cm3) was associated with lower PFS in multivariate analysis, independently of TRT (HR=0.41 [0.2-0.85], p=0.02). All grades TRT-related adverse events were similar between the groups, except for an excess of febrile neutropenia (5.3% vs 5.3% vs 24.4%, p&lt;0.001) and mucositis (1.8% vs 3.9% vs 22.8%, p&lt;0.001) in the ACVBP group. Twenty-two pts died (CHOP21: n=8, ACVBP: n=14) mainly due to lymphoma progression (n=15; 68.2%). 2 toxic deaths were observed (CHOP21: n=1, ACVBP: n=1). Secondary malignancies appeared in 7 pts (CHOP21: n=2, ACVBP: n=5), including 3 cases of acute myeloid leukemia. Conclusion These results confirm the favorable outcome of PMBL pts treated with CHOP14 and ACVBP plus anti CD20 Ab. The toxicity of ACVBP was more pronounced and CHOP14 was associated with a better OS. Baseline TMTV≥360cm3 is a highly predictive factor of unfavorable outcome in PMBL pts, independently of TRT. We recommend R-CHOP14 as standard of care in PMBL. Figure Disclosures Camus: ROCHE: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); PFIZER: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); AMGEN: Honoraria; JANSSEN: Honoraria. Decazes:Bayer: Other: travel, accomodations, expenses. Bernard:Janssen: Other: Travel and accommodation . Gandhi Laurent:Abbevie, Pfizer, Takeda, Roche: Other: Travel; Roche, Takeda, Iqone, Accord: Consultancy; Roche, Takeda, Accord: Honoraria. Laribi:amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding; abbvie: Honoraria, Research Funding. Houot:Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; MSD: Honoraria. Tilly:BMS: Honoraria.

BackgroundInterstitial lung disease (ILD) is a severe complication of rheumatoid arthritis (RA). Abatacept and rituximab are the preferred disease-modifying antirheumatic drugs (DMARDs) for RA-ILD[1-4]. However, progression of ILD despite its use is not uncommon. A subgroup analysis of the INBUILD trial has shown a slower decline in forced vital capacity (FVC) in patients with progressive fibrosing autoimmune disease-related ILDs with the antifibrotic nintedanib (NINTE)[5].ObjectivesA) To assess the efficacy of antifibrotic drugs, NINTE and pirfenidone (PIRFE), in Spanish RA-ILD patients with a progressive phenotype in clinical practice.B) To compare the profile of clinical practice RA-ILD patients with the RA-ILD patients included in the INBUILD trial[5].MethodsNational multicenter study of RA-ILD patients to whom NINTE or PIRFE were added due to progressive fibrosing ILD. Demographic and clinical variables were collected from all patients. These features were compared with those of RA-ILD patients included in the INBUILD trial (n=89, 42 treated with NINTE and 47 with placebo). Forced vital capacity (FVC) evolution was the primary endpoint. Results are expressed as percentage, mean±SD or median [IQR].ResultsA total of 50 patients (19 women/31 men) from clinical practice were collected (NINTE=45, PIRFE=5), mean age 70±8 years. Median ILD duration up to antifibrotic initiation was of 45 [19-72] months. Mean FVC one year before antifibrotic start was 81±20 (% pred.), whilst mean baseline FVC was 72±23 (% pred.). Comparison of baseline characteristics of RA-ILD patients treated with NINTE in clinical practice (n=45) and RA-ILD patients of the INBUILD trial is shown inTable 1. The evolution of FVC and DLCO in our patients from the previous year of antifibrotic initiation is shown inFigure 1.After a median follow-up of 16 [5-24] months, no decline in mean FVC and DLCO values was observed. Stabilization or improvement of dyspnea was found in 83% of patients. NINTE was withdrawn in 8 patients due to: gastrointestinal adverse events (GAE) (n=6), death (n=1) or hemorrhage risk (n=1). PIRFE was withdrawn in 2 patients due to GAE.ConclusionAntifibrotics, specially NINTE, seem to slow ILD progression in patients with RA-ILD. In clinical practice, patients are treated later in the evolution of the disease, but results are satisfactory. Combination of antifibrotics and DMARDs in RA-ILD is possible and safe.References[1]Autoimmun Rev.2021 Jun;20(6):102830[2]Rheumatology.2020 Dec 1;59(12):3906-3916[3]Rheumatology.2021 Dec 24;61(1):299-308[4]J Clin Med.2020 Sep 23;9(10):3070[5]Arthritis Rheumatol.2022 Jun;74(6):1039-1047Table 1.Baseline characteristics of RA-ILD patients treated with NINTE in clinical practice and RA-ILD patients of the INBUILD trial.Clinical practice (n=45)INBUILD trial (n=89, 42 NINTE vs 47 PCB)Age, years mean±SD70±867±10Women, n (%)18 (40)35 (39.3)Smoker ever, n (%)34 (76)57 (64)Time since ILD diagnosis, years mean±SD4.6±4.43.6±3.2RF, n (%)40 (89)-ACPA, n (%)37 (82)FVC (% pred) mean±SD72±2472±16DLCO (% pred) mean±SD51±1548±16Dyspnea mMRC median [IQR]2 [2-3]-UIP-like fibrotic pattern on HRCT, n (%)31 (69)77 (86)Concomitant IS therapy, n (%)45 (100)79 (89)Glucocorticoids34 (76)-cDMARD14 (31)bDMARD19 (42)JAKi4 (9)Figure 1.Evolution of FVC and DLCO in patients with RA-ILD treated with antifibrotics in clinical practice from the previous year of initiation.Members of the Spanish Collaborative Group of Antifibrotics in RA-ILD:Juan Ramón de Dios (HU Araba), Libe Ibarrola (HU de Navarra), Carmen Gonzalez Montagut (HCU de Valladolid), Sergi Ordoñez (H. Arnau de Vilanova), Anahy Mª Brandy (HU Cabueñes), Fernando Lozano (HCD Gómez Ulla), Maria López Lasanta (HU Vall d’Hebron), Cristina Campos (CHGU de València), Marta Garijo (H. de Sagunto), Ivette Casafont (HU Germans Trias i Pujol), Mónica Calderón (H. José Molina Orosa), Carlota Iñiguez (HU Lucus Augusti), Francisco Ortiz-Sanjuán (HUP La Fe), Emilio Giner (H. Royo Villanova), Ignacio Braña (HU Central de Asturias).Acknowledgements:NIL.Disclosure of InterestsBelén Atienza-Mateo: None declared, Ana Serrano-Combarro: None declared, MARIA MARTIN LOPEZ: None declared, Santos Castañeda: None declared, Rafael Melero: None declared, Jesús Loarce-Martos: None declared, Natalia Mena-Vázquez: None declared, Maria del Carmen Carrasco Cubero: None declared, Carolina Díez: None declared, David Castro-Corredor: None declared, Tomas Vazquez Rodriguez: None declared, Andrea García-Valle: None declared, Gemma Bonilla: None declared, Marina Rodriguez Lopez: None declared, Diego Ferrer: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, lilly, Bristol-Myers, Janssen, Galapagos and MSD, Consultant of: bbvie, Pfizer, Roche, lilly, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD, novartis and Roche.

Abstract Background/Aims Filgotinib (FIL) is an oral, potent, selective Janus kinase 1 (JAK1) inhibitor. FINCH 1 (NCT02889796) assessed FIL efficacy, safety and patient reported outcome (PRO) data in patients (pts) with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX-IR). We report data through week 52 (W52) of the FINCH 1 study. Primary outcome results at week (W)12 and W24 were previously reported. Methods This global, phase 3, double-blind, active- and placebo (PBO)-controlled study randomised MTX-IR pts with active RA on a background of stable MTX 3:3:2:3 to oral FIL 200 mg or FIL 100 mg once daily, subcutaneous adalimumab (ADA) 40 mg every 2W, or PBO up to W52; pts receiving PBO at W24 were re-randomised to FIL 100 or 200 mg. Efficacy was assessed using clinical, radiographic, and pt-reported outcomes; W52 comparisons were not adjusted for multiplicity, and nominal p-values are reported. Safety endpoints included types and rates of adverse events (AEs) and laboratory abnormalities. PRO assessment included the HAQ-DI and VAS pain scale, SF-36, and FACIT-Fatigue questionnaire. Change from baseline (CFB) at various time points was assessed up to W52 for each treatment group. Results Of 1,755 treated pts, 1,417 received study drug through W52. FIL efficacy was sustained through W52 with DAS28(CRP) &lt;2.6 remission rates of 54%, 43%, and 46% of pts receiving FIL 200 and 100 mg and ADA, respectively, (nominal p for FIL 200 vs ADA = 0.024) (Table 1). FIL safety profile through W52 was consistent with W24 data. AEs of interest were infrequent and balanced among treatments. As early as W2, through W24, pts receiving either dose of FIL experienced nominally significantly greater (p &lt; 0.001) CFB in HAQ-DI and VAS pain scale than those receiving PBO. These improvements were sustained up to W52. In general, CFB for HAQ-DI, VAS pain scale, and FACIT-Fatigue observed for the FIL groups was higher or comparable to ADA through W52 (Table 1). P133 Table 1:Efficacy and PRO outcomes at Week 52Efficacy OutcomeFIL 200 mg (n = 475)FIL 100 mg (n = 480)ADA (n = 325)ACR20/50/70, %a78/62/4476/59/3874/59/39DAS28(CRP) ≤3.2, %a66+5959mTSSb,c0.18+++0.450.61HAQ-DIc,d−0.93+−0.85−0.85VAS pain scalec,d−42−40−40SF-36 PCSc,d12.011.512.4FACIT-Fc,d11.912.211.7aNon-responder imputation,bLeast squares mean change from baseline,cObserved case,dMean change from baseline.+nominal p &lt; 0.05, +++nominal p &lt; 0.001 vs ADA ADA, adalimumab; FACIT-F, Functional Assessment of Chronic Illness Therapy Fatigue; FIL, filgotinib; HAQ-DI, Health Assessment Questionnaire-Disability Index; mTSS, modified van der Heijde TSS; SF-36, 36-Item Short Form Survey. Conclusion Through W52, both FIL 200 and 100 mg showed sustained efficacy, rapid and sustained improvement in patient QoL based on clinical and pt-reported outcomes and were well tolerated in MTX-IR pts with RA. Disclosure D. Walker: Consultancies; Lilly, Pfizer, Novartis, Roche. A. Kivitz: Consultancies; AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc. Shareholder/stock ownership; Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis. Member of speakers’ bureau; Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie. Y. Tanaka: Honoraria; AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead Sciences, Inc., GlaxoSmithKline, Janssen, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sanofi and Y. Grants/research support; AbbVie, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Takeda and UCB. S. Lee: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. L. Ye: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. H. Hu: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. F. Matzkies: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. B. Bartok: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. B. Bartok: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. Y. Guo: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. J.S. Sundy: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. A. Jahreis: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. R. Besuyen: Shareholder/stock ownership; Galapagos BV. Other; Employee of Galapagos BV. B. Combe: Other; Reports research support, honoraria, consulting and speaker fees from AbbVie; Bristol-Myers Squibb; Eli Lilly & Co.; Gilead Sciences, Inc.; Janssen; Novartis; Pfizer; Roche-Chugai; Sanofi; and UCB. D. van der Heijde: Consultancies; AbbVie; Amgen; Astellas; AstraZeneca; Bristol-Myers Squibb; Boehringer Ingelheim; Celgene; Cyxone; Daiichi-Sankyo; Eisai; Eli Lilly & Co.; Galapagos; Gilead Sciences, Inc.; Glaxo-Smith-Kline; Janssen;, Merck; Novartis; Pfizer; Regeneron; Roche; Sanofi; Takeda; and UCB. J. Simon-Campos: None. H.S.B. Baraf: Grants/research support; AbbVie; Horizon; Gilead Sciences, Inc.; Pfizer; Janssen; and Merck. U. Kumar: None. C. Tasset: Shareholder/stock ownership; Galapagos NV. Other; Employee of Galapagos NV. N. Mozaffarian: Shareholder/stock ownership; Gilead Sciences, Inc. Other; Employee of Gilead Sciences, Inc. R.B.M. Landewé: Consultancies; AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Gilead Sciences, Inc.; Galapagos NV; Novartis; Pfizer; and UCB. S. Bae: None. E. Keystone: Other; Reports research support, consulting, and speaker fees from AbbVie; Amgen; AstraZeneca; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen; Lilly, ; Merck; Myriad Autoimmune; Pfizer; PuraPharm; Sandoz; Sanofi-Genzyme; Samsung Bioepsis; and UCB. P. Nash: Other; Reports research support, consulting, and speaker and personal fees from AbbVie; Bristol-Myers Squibb; Celgene; Eli Lilly & Co.; Gilead Sciences, Inc; Janssen; Merck Sharp & Dohme; Novartis; Pfizer;, Roche; Sanofi; and UCB.

Introduction: Major abdominal surgery predisposes to hyperglycemia due to metabolic stress, inflammation, perioperative nutrition support and medication. The aim of the study was to assess the efficacy of fully closed-loop (FCL) versus usual care (UC) insulin delivery for glycemic management in major abdominal surgery patients. Methods: In this randomized controlled trial (NCT05392452) we compared perioperative use of the CamAPS HX FCL system (Dexcom G6, YspoPump, SC faster insulin aspart) with UC insulin treatment from admission until hospital discharge (max 20 days) at two tertiary hospitals in Switzerland. The primary endpoint was % time in sensor glucose target range (5.6-10.0mmol/L). Results: Thirty-seven patients (FCL n=18, UC n=19, 27% female, mean±SD age 66±12 years, BMI 27.8±5.7 kg/m2, HbA1C 6.9±1.0 %) were analyzed. Mean±SD % time in target glucose range (5.6-10.0mmol/L) was 80.1±10.0 % with FCL vs 53.7±19.7 % with UC (p&lt;0.001). Time in hypoglycemia (&lt;3.9mM and &lt;3.0mM) did not differ between groups. Total daily insulin dose was significantly higher in the FCL vs UC group (p&lt;0.001). Conclusions: Perioperative use of FCL insulin delivery in major abdominal surgery patients with complex medical needs results in significantly better glucose control compared to standard insulin therapy without increasing the risk of hypoglycemia. Disclosure G. Krutkyte: None. A. Goerg: None. C.A. Grob: None. G. Beldi: None. A. Wenning: None. R. Hovorka: Other Relationship; CamDiab. Research Support; Abbott, Dexcom, Inc., Ypsomed AG. Speaker's Bureau; Ypsomed AG, Abbott, Novo Nordisk, Novartis Pharmaceuticals Corporation. M.E. Wilinska: Consultant; CamDiab. D. Herzig: Speaker's Bureau; Ypsomed AG. A. Vogt: None. T. Girard: None. L. Bally: None. Funding Helmut Horten FoundationScherbarth Foundation and intramural grants of the Department of Anaesthesiology and Pain Medicine, University Hospital BernSwiss Foundation for Anaesthesiology and Intensive CareClinic for Anaesthesiology, University Hospital BaselFreiwillige Akademische Gesellschaft Basel

Abstract Background Outpatient treatment with SARS-CoV-2–neutralizing antibody combination AZD7442 (tixagevimab/cilgavimab) in adults with mild to moderate COVID-19 significantly reduced progression to severe disease or death through Day 29 and was well-tolerated in the Phase 3 TACKLE study (NCT04723394). We report a post hoc analysis of the impact of AZD7442 in reducing self-reported COVID-19 symptom severity and time to symptom resolution through Day 29 in TACKLE. Methods In TACKLE, non-hospitalized adults with mild to moderate COVID-19 were randomized 1:1 and dosed ≤7 days from symptom onset with a single 600mg AZD7442 dose (2 consecutive intramuscular (IM) injections, 300 mg of each antibody; n=452) or placebo (n=451). Symptom occurrence and severity were self-reported daily by participants through study Day 29. Participants rated each symptom as not experienced, mild, moderate, severe, or emergency room (ER) or hospital visit. Symptom progression was compared between AZD7442 and placebo using a stratified Cochran-Mantel-Haenszel test. Change from baseline in symptom severity was compared using a mixed model for repeated measures. Time to symptom resolution was compared using Kaplan-Meier and Cox proportional hazards methods. Missing symptom data for those who were hospitalized or died were imputed as either failures or as severity scores of ER or hospital visit. Results Progression of ≥1 symptoms to a worse severity score occurred in 170 (55.7%) AZD7442- versus 204 (63.4%) placebo-treated participants, translating to a nominally significant relative risk reduction of 12.5% (95% confidence interval 0.5–23.0; P=0.041). Over 29 days, the overall mean improvement from baseline in severity of body aches, chills, cough, diarrhea, fatigue, headache, muscle aches, nausea, and runny nose was significantly greater with AZD7442 versus placebo (Figure). The greatest improvements were observed with cough, fatigue, and muscle aches. Significant differences were observed for most symptoms within 1 and 2 weeks post AZD7442 dosing. Figure. Forest plot for LS difference in severity of COVID-19 symptoms between AZD7442 and placebo through Day 29 CI, confidence interval; LS, least squares. The overall P value is calculated using a mixed model for repeated measures, including terms for symptom severity baseline value, time from symptom onset (≤5 vs &gt;5 days), risk of progression to severe COVID-19 (high vs low), treatment, visit, and treatment by visit interaction. Conclusion For the treatment of mild to moderate COVID-19, a single IM 600-mg AZD7442 dose was associated with reductions in progression of COVID-19 symptom severity and may hasten symptom improvement through Day 29. Disclosures Jesus Abraham Simón Campos, MD, AstraZeneca: Board Member|AstraZeneca: Speaker|Eli Lilly: Board Member|Pfizer: Board Member|Roche: Board Member|Roche: Speaker Douglas Arbetter, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Hugh Montgomery, MD, AstraZeneca: Advisor/Consultant|Millfield Medical Ltd: Advisor/Consultant|UK National Institute for Health Research's Comprehensive Biomedical Research Centre at University College London Hospitals: Grant/Research Support F.D. Richard Hobbs, FMedSci, AstraZeneca: Grant/Research Support|AstraZeneca: Principal investigator|NIHR Applied Research Collaboration, Oxford Thames Valley: Director|Oxford BRC and NIHR MedTech: Investigator|UKRI and NIHR: Grant/Research Support Francisco Padilla, MD, Amgen: Grant/Research Support|Amgen: Personal fees|AstraZeneca: Grant/Research Support|AstraZeneca: Personal fees|Boehringer Ingelheim: Grant/Research Support|Boehringer Ingelheim: Personal fees|Ferrer: Grant/Research Support|Ferrer: Personal fees|Kowa: Grant/Research Support|Kowa: Personal fees|Medix: Grant/Research Support|Medix: Personal fees|Merck Sharp and Dohme: Grant/Research Support|Merck Sharp and Dohme: Personal fees|Novartis: Grant/Research Support|Novartis: Personal fees|Pfizer: Grant/Research Support|Pfizer: Personal fees|Sanofi: Grant/Research Support|Sanofi: Personal fees|Servier: Grant/Research Support|Servier: Personal fees|Silanes: Grant/Research Support|Silanes: Personal fees Kenneth Kim, MD, Adagio: Funding|Eli Lilly: Funding|Merck: Funding|Pfizer: Funding|Regeneron: Speaker|Regeneron: Funding Katie Streicher, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Alison Templeton, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Rolando M. Viani, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Mark T. Esser, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds.

Abstract Background Outpatient treatment with SARS-CoV-2–neutralizing antibody combination AZD7442 (tixagevimab/cilgavimab) in adults with mild to moderate COVID-19 significantly reduced progression to severe disease or death through Day 29 and was well-tolerated in the Phase 3 TACKLE study primary analysis (NCT04723394). AZD7442 administered earlier in the disease course leads to more favorable outcomes and has the potential to prevent COVID-19 hospitalizations and reduce hospital burden. We report key secondary efficacy results with longer-term safety data from TACKLE over 6 months. Methods In TACKLE, non-hospitalized adults with mild to moderate COVID-19 were randomized 1:1 and dosed ≤7 days from symptom onset with a single 600-mg AZD7442 dose (2 consecutive intramuscular injections, 300 mg of each antibody; n=452) or placebo (n=451). The key secondary endpoint was death from any cause or hospitalization for COVID-19 complications or sequelae through Day 169, analyzed using a Cochran-Mantel-Haenszel test stratified by time from symptom onset and risk of severe COVID-19 progression. Results Death from any cause or hospitalization for COVID-19 complications or sequalae occurred in 20 (5.0%) versus 40 (9.8%) participants receiving AZD7442 versus placebo, respectively, translating to a relative risk reduction (RRR) of 49.1% (95% confidence interval [CI] 14.5–69.7) versus placebo (P=0.009). A sensitivity analysis excluding participants who were unblinded prior to Day 169 for consideration of vaccination yielded a similar RRR of 50.7% (95% CI 17.5–70.5; P=0.006). For baseline seronegative participants, an RRR of 58.6% (95% CI 27.6–76.4; P=0.001) was observed. The median (range) safety follow-up was 170 (1–330) days with AZD7442 and 170 (1–326) days with placebo. Adverse events occurred in 38.5% of AZD7442 participants and 43.5% of placebo participants, and were mostly mild to moderate. Conclusion A single 600-mg AZD7442 dose demonstrated statistically significant protection against death from any cause or hospitalization for COVID-19 through 6 months, and was well-tolerated. These data provide further support of AZD7442 in the COVID-19 outpatient treatment setting, with potential to reduce hospital burden. Disclosures F.D. Richard Hobbs, FMedSci, AstraZeneca: Grant/Research Support|AstraZeneca: Principal investigator|NIHR Applied Research Collaboration, Oxford Thames Valley: Director|Oxford BRC and NIHR MedTech: Investigator|UKRI and NIHR: Grant/Research Support Hugh Montgomery, MD, AstraZeneca: Advisor/Consultant|Millfield Medical Ltd: Advisor/Consultant|UK National Institute for Health Research's Comprehensive Biomedical Research Centre at University College London Hospitals: Grant/Research Support Francisco Padilla, MD, Amgen: Grant/Research Support|Amgen: Personal fees|AstraZeneca: Grant/Research Support|AstraZeneca: Personal fees|Boehringer Ingelheim: Grant/Research Support|Boehringer Ingelheim: Personal fees|Ferrer: Grant/Research Support|Ferrer: Personal fees|Kowa: Grant/Research Support|Kowa: Personal fees|Medix: Grant/Research Support|Medix: Personal fees|Merck Sharp and Dohme: Grant/Research Support|Merck Sharp and Dohme: Personal fees|Novartis: Grant/Research Support|Novartis: Personal fees|Pfizer: Grant/Research Support|Pfizer: Personal fees|Sanofi: Grant/Research Support|Sanofi: Personal fees|Servier: Grant/Research Support|Servier: Personal fees|Silanes: Grant/Research Support|Silanes: Personal fees Kenneth Kim, MD, Adagio: Funding|Eli Lilly: Funding|Merck: Funding|Pfizer: Funding|Regeneron: Speaker|Regeneron: Funding Jesus Abraham Simón Campos, MD, AstraZeneca: Board Member|AstraZeneca: Speaker|Eli Lilly: Board Member|Pfizer: Board Member|Roche: Board Member|Roche: Speaker Douglas Arbetter, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kelly W. Padilla, PharmD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Venkatesh P. Reddy, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Seth Seegobin, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Katie Streicher, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Rolando M. Viani, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Gavin CKW Koh, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Mark T. Esser, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds.

Abstract Background In the TACKLE phase 3 outpatient treatment study, 600-mg AZD7442 (tixagevimab/cilgavimab) in adults with mild to moderate COVID-19 significantly reduced progression to severe disease or death over 29 days and was well-tolerated at primary analysis. Here, we report final safety findings from TACKLE. Methods In TACKLE (NCT04723394), non-hospitalized adults with mild to moderate COVID-19 were randomized 1:1 and dosed ≤7 days from symptom onset with 600-mg AZD7442 (N=452) or placebo (N=451). Results are reported from the January 22, 2023 final data cut-off. The primary safety endpoint was assessment of adverse events (AEs), serious adverse events (SAEs), and AEs of special interest (AESIs). A cardiovascular events adjudication committee independently evaluated 5 event types (cardiac ischemia, cardiovascular death, heart failure, stroke, and thrombotic events). Results Across both the AZD7442 and placebo groups, 797 (87.6%) participants completed the study. Median follow-up was ∼15 months or 458.5 days in the AZD7442 group and 458.0 days in the placebo group. AEs occurred in 251 (55.5%) and 252 (55.9%) of participants administered AZD7442 and placebo, respectively (Table). The most common AEs were COVID-19, post-acute COVID-19 syndrome, and COVID-19 pneumonia. Reinfection with COVID-19 within 6 months occurred in 1 (0.2%) and 2 (0.4%) participants in the AZD7442 and placebo groups, respectively (all other COVID-19 AEs were judged to be sequelae from the original event). Most AEs were mild to moderate in severity; 33 (7.3%) and 51 (11.3%) of participants in the AZD7442 and placebo groups, respectively, reported an AE of grade 3 (severe) or 4 (life-threatening). SAEs occurred in 46 (10.2%) and 65 (14.4%) AZD7442 and placebo participants, and deaths in 8 (1.8%) and 8 (1.8%), respectively. AESIs occurred 4.2% and 3.8% of AZD7442 and placebo participants, respectively, including 0.4% and 0.2% with cardiovascular disorders categorized as AESIs. Cardiovascular events occurring in 4 (0.9%) participants in both groups were evaluated by an adjudication committee, with 1 (0.2%) participant in both groups having a positively adjudicated event. Conclusion This analysis provides further evidence of the long-term safety of AZD7442 as treatment for COVID-19. Disclosures F.D. Richard Hobbs, FMedSci, AstraZeneca: Grant/Research Support|National Institute for Health and Care Research: Grant/Research Support|UK Research and Innovation: Grant/Research Support Hugh Montgomery, MD, AstraZeneca: Advisor/Consultant|Millfield Medical Electronics Ltd: Advisor/Consultant Francisco Padilla, MD, Amgen: Grant/Research Support|AstraZeneca: Grant/Research Support|Boehringer Ingelheim: Grant/Research Support|Ferrer: Grant/Research Support|Kowa: Grant/Research Support|Medix: Grant/Research Support|Merck: Grant/Research Support|Merck Sharp and Dohme: Grant/Research Support|Novartis: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support|Servier: Grant/Research Support|Silanes: Grant/Research Support Jesus Abraham Simón Campos, MD, AstraZeneca: Expert Testimony|Atea: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Pfizer: Expert Testimony|Regeneron: Expert Testimony|Roche: Expert Testimony Douglas Arbetter, MPH, AstraZeneca: Employement|AstraZeneca: Stocks/Bonds Seth Seegobin, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Alexandre Kiazand, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Katie Streicher, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Nuria Martinez-Alier, PhD, AstraZeneca: Employee|AstraZeneca: Employement|AstraZeneca: Stocks/Bonds|AstraZeneca: Stocks/Bonds Taylor Cohen, PhD, AstraZeneca: Employement|AstraZeneca: Stocks/Bonds Mark T. Esser, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds