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1
Noble, Kenneth. "“A More Meaningful Democracy than We Ourselves Possess”: Charles S. Johnson and the Education Mission to Japan, 1945–1952." History of Education Quarterly 54, no. 4 (November 2014): 405–28. http://dx.doi.org/10.1111/hoeq.12077.
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“Recommendations in the report,” stated Charles S. Johnson, “have implications for our own educational system, and perhaps for our own society.” Johnson, a sociologist and Fisk University's first African-American president, addressed the 1948 South Central Forum in Chicago discussing the fundamental inconsistencies existing between democracy recommended in occupied Japan's education system and the democracy practiced in America's education system. The report Johnson's speech refers to was the product of the Education Mission to Japan: a twenty-seven-member American committee selected for their expertise as educators and scholars. Charged with an advisory role to the Supreme Commander of the Allied Powers (SCAP) and the Japanese Ministry of Education (JME), the committee's primary objective extended from SCAP's overall mission: to democratize and mollify postwar Japan. Johnson, a civil rights advocate and race relations scholar, was the sole African American and only nonwhite member of this committee.
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Stein, Glenn M. "The first African-American in Antarctica: George W. Gibbs Jr." Polar Record 46, no. 3 (May 11, 2010): 281–82. http://dx.doi.org/10.1017/s0032247409990507.
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On 2 September 2009, the Advisory Committee on Antarctic Names (US Board on Geographic Names) confirmed a place name for George Washington Gibbs Jr, the first African-American expedition member to set foot on the Antarctic continent (Fig. 1). Gibbs Point forms the northwest entrance to Gaul Cove, on the northeast of Horseshoe Island, Marguerite Bay, Antarctic Peninsula (67°48′22″S, 67°09′38″W) (Fig. 2).
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Joseph, Nisha, Vikas A. Gupta, Craig C. Hofmeister, Charise Gleason, Leonard Heffner, Lawrence H. Boise, Jonathan L. Kaufman, Madhav V. Dhodapkar, Sagar Lonial, and Ajay K. Nooka. "Differences in Presentation and Survival Outcomes for African American Patients with Newly Diagnosed Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 5647. http://dx.doi.org/10.1182/blood-2018-99-119948.
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Abstract Background : Though the incidence of MM is two- to threefold higher in the African American (AA) population compared to Caucasians, reported long term outcomes are less favorable presumably due to inequities in access to healthcare. Little is known about the biology or disease presentation among AAs. We have conducted a retrospective analysis of our institutional data of 1000 patients treated with RVD induction therapy, specifically assessing differences in presentation, disease biology, and outcomes in AA patients. Methods: A total of 1000 newly diagnosed MM patients were treated with RVD induction therapy [R - 25 mg/day (days 1-14), V - 1.3 mg/m2 (days 1, 4 8, 11) and D - 40 mg once/twice weekly as tolerated every 21 days] from January 1st 2005 until August 31st 2016. Dose-adjustments were made based on the treating physician's discretion and patient tolerability. Demographic and outcomes data for the patients were obtained from our IRB approved myeloma database and responses were evaluated per IMWG Uniform Response Criteria. Results: Of the 1000 patients included in the analysis, 564 (56.4%) of patients were white (W), and 339 (33.9%) were AA, consistent with the demographic representation of the state of GA and our institutional referral population. Median age of this cohort was 61 years (range 16-83), 57 for AA patients (range, 24-83) compared to 62 (range, 16-81) in white patients, suggesting the onset is earlier among AA which has been previously reported in population based studies. Other notable characteristics include: 42.5%M/57.5% F for AA cohort and 61.7%M/38.3%F for white cohort. In regard to stage, AA: 73.9% stage I/II, 26.1% stage III; W: 77.1% stage I/II, 22.9% stage III, showing no difference in prognostic staging at presentation. There was no statistically significant difference in the presenting labs between AA and whites except for hemoglobin, with more AA patients presenting with Hgb≤9.9 g/dL (45.7% AA vs 32.5% W, p <.0001). In terms of prevalence of high-risk cytogenetics, there was no significant difference between the two cohorts in: complex karyotype 16% white/14.4% AA; t(14;16) 2.4% W/2.8% AA; t(4;14) 4.7% W/5.0% AA; t(11;14) 11.7% W/15.9% AA; or del1p 6.5%W/7.8%AA. However, there were significant differences found in the rates of: amp 1q 19.2% W/10.6% AA, (p<.0001), del13 28.3% W/19.6% AA (p=.003), and del17p 11.7% W/7.2% AA (p=.019), all three significantly less frequent in AAs. Median time to transplant for the entire cohort was 5 months (range, 1-124), and median time to best response was 3 months (range, 0-39). There was no significant difference in the number of patients who underwent ASCT (84% W vs 82% AA, p=.241), nor in ≥VGPR rates post-induction and 100 days post-ASCT: 69.9% W vs 64.5% AA (p=.056) and 88.1% W vs 86.7% in AA patients (p=.317), respectively. Median PFS for the entire cohort was 63 months, 62 months (54-69.9) for white patients versus 65 months (53-76.9) for AA patients (p=0.403). At a median follow up of 38 months, median OS has not yet been reached. Conclusions: This is the largest reported cohort of myeloma patients treated with RVD induction, with one-third of the patients representing the AA population. In our dataset, AAs are diagnosed 5 years younger, with lower hemoglobin at presentation and lower rates of amp1q, del13 and del17p when compared to whites. When offered the same induction regimen and opportunity for ASCT, AAs tend to experience the same survival benefits as their white counterparts. The lack of significant difference in PFS or OS suggests standardization and improved access to care could lead to better long-term outcomes in the AA population. Disclosures Hofmeister: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Heffner:Genentech: Research Funding; Pharmacyclics: Research Funding; ADC Therapeutics: Research Funding; Kite Pharma: Research Funding. Boise:AstraZeneca: Honoraria; Abbvie: Consultancy. Kaufman:BMS: Consultancy; Janssen: Consultancy; Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Roche: Consultancy. Lonial:Amgen: Research Funding. Nooka:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Reverby, Susan M. "“Special Treatment”: BiDil, Tuskegee, and the Logic of Race." Journal of Law, Medicine & Ethics 36, no. 3 (2008): 478–84. http://dx.doi.org/10.1111/j.1748-720x.2008.294.x.
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The presence of the Tuskegee Syphilis Study was palpable at the June 16, 2005, Food and Drug Administration’s (FDA) Advisory Committee meeting on BiDil, a heart medication from the pharmaceutical company NitroMed that sought approval as the first race-specific drug. So ubiquitous is the restless and unsettled spirit of Tuskegee that it continues to hover over the African American public and the biomedical research/health care provider communities more than three and a half decades after the actual study “died.” No one invoked the word “Tuskegee” in that dimly lit meeting room as BiDil gained the Advisory Committee’s approval. Yet its power was exerted even when it was not named. The FDA Committee’s chairman, Cleveland Clinic cardiology chief Steven Nissen, acknowledged this after the committee met: “We were putting [Tuskegee]…to rest.”
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Leger, Paul Denis, Stanley K. Frencher, Jones T. Nauseef, Brian Jones, Lansing Scriven, Che-Kai Tsao, Mehmet Asim Bilen, et al. "Assessing barriers to prostate cancer clinical trial participation among Black and African Americans: A multi-perspective qualitative study." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): e13682-e13682. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.e13682.
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e13682 Background: Prostate cancer affects non-Hispanic Black people at a higher rate than other groups, including non-Hispanic White people and Hispanic people. However, Black and African American patients are historically underrepresented in prostate cancer clinical trials. Using a multi-perspective qualitative approach (physicians, advocates, and patients), we aimed to better understand the barriers to Black and African American participation in prostate cancer clinical trials. Methods: Three advisory boards were conducted with each advisory board consisting of a unique stakeholder: (1) physicians, (2) patient advocates, and (3) patients. The physician advisory board included 5 medical oncologists, 1 radiation oncologist, and 1 urologist. The patient advocate advisory board included 7 patient advocates focused on increasing healthcare equity in prostate cancer. The patient advisory board included 7 Black and African Americans with prostate cancer. The median patient age was 65 years (range: 60-73). Each advisory board was a 2-hour virtual meeting, with a moderated discussion to deepen the understanding of enrollment obstacles and identify strategies to increase diverse enrollment in prostate cancer clinical trials. All participants were compensated for their time. Results: We identified five key themes describing barriers to diverse prostate cancer clinical trial enrollment: (1) systemic healthcare system barriers including lack of insurance or underinsurance, difficult to navigate healthcare systems, and lack of caregiver support structures; (2) the lack of trust in clinical research due to historical injustices; (3) stigma and lack of education around prostate cancer; (4) the importance of female caregivers; and (5) lack of time, incentive, and funding from trial sponsors for institutions to develop and execute strategies to enroll diverse patients. We also identified opportunities for improving diversity in prostate cancer clinical trials. These include allowing additional start-up time and sponsor funding for sites to develop unique diversity-focused enrollment strategies, sponsors encouraging diverse enrollment by considering steering committee appointments that can provide expertise in enrolling diverse patients, and building trust by engaging Black and African American community organizations, such as churches and fraternities/sororities, including female caregivers. Conclusions: Shared themes emerged from the 3 advisory boards that both validated prior knowledge and identified new areas of emphasis for reducing health inequities and low enrollment among Black and African Americans in prostate cancer clinical trials. In addition, the multiple perspectives represented by the advisory boards led to specific ideas and strategies for institutions to consider implementing for future trials.
6
Odiete, Oghenerukevwe, Olagoke Akinwande, John J. Murray, and Joseph Akamah. "Pneumococcal Tricuspid Valve Endocarditis in a Young African American: A Case for Inclusion of African Americans in Pneumococcal Vaccine Criteria." Case Reports in Medicine 2010 (2010): 1–4. http://dx.doi.org/10.1155/2010/982521.
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Following the development of penicillin, complications from streptococcus pneumonia such as endocarditis have become rare. However, certain independent risk factors such as cigarette smoking and being of African-American (AA) decent have been associated with a higher incidence of invasive pneumococcal disease, but only cigarette smoking has been targeted by current recommendations from the Advisory Committee on Immunological Practices (ACIPs). We report a case of a young AA smoker, who developed an isolated tricuspid valve pneumococcal endocarditis. This case will illustrate the high susceptibility for invasive pneumococcus sequelae in AA, thereby raising the argument for the consideration of AA in the Pneumococcal Conjugate Vaccine (PCV) criteria, regardless of smoking history.
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Heeney, Matthew M., David C. Rees, Mariane de Montalembert, Isaac Odame, R. Clark Brown, Yasser Wali, Thu Thuy Nguyen, Du Lam, Raquel Merino Herranz, and Julie Kanter. "Study Design and Initial Baseline Characteristics in Solace-Kids: Crizanlizumab in Pediatric Patients with Sickle Cell Disease." Blood 136, Supplement 1 (November 5, 2020): 22–24. http://dx.doi.org/10.1182/blood-2020-137081.
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Background: Sickle cell disease (SCD) is a group of genetic blood disorders characterized by hemolytic anemia, multi-organ damage and acutely painful events (vaso-occlusive crises [VOCs]) that can cause life-threatening complications. Vaso-occlusion is mediated, in part, by P-selectin, an adhesion molecule expressed on endothelial cells and platelets. Adults and children with SCD have similar P-selectin expression levels; however, disease severity worsens with increasing age because of cumulative endothelial damage caused by repeated vaso-occlusion events. Crizanlizumab is a humanized anti-P-selectin monoclonal antibody that binds P-selectin and blocks its interaction with its ligands. SUSTAIN, a Phase 2 study in adults with SCD, has shown that crizanlizumab, compared with placebo, is well tolerated and significantly decreases the number of VOCs requiring a healthcare visit (Ataga et al. N Engl J Med 2017). Aim: To describe the design of the first crizanlizumab study in pediatric patients (pts) with SCD and report demographics and baseline characteristics of a subset of enrolled pts (aged 6 to <18 yr) (ClinicalTrials.gov: NCT03474965). Methods: Primary objectives of this Phase 2, multicenter, open-label study are to confirm crizanlizumab dosing and assess safety. Pts aged 6 mo to <18 yr with a confirmed SCD diagnosis (any genotype) and ≥1 VOC within the preceding 12 mo are included. The study will enroll ≥100 pts in 3 age groups: Group 1 (G1; 12 to <18 yr), 2 (G2; 6 to <12 yr), and 3 (G3; 6 mo to <6 yr). Crizanlizumab is administered intravenously on weeks 1 and 3, and every 4 weeks thereafter for up to 2 years. Dose confirmation is being determined by single- and multiple-dose pharmacokinetic (PK) data and key safety data. Steady state PK, pharmacodynamic (PD) and safety data are used to validate the confirmed dose or prompt modifications, if required. Secondary objectives include assessment of crizanlizumab efficacy, measured by annualized rate of VOCs leading to a healthcare visit (clinic, emergency room [ER] or hospital), and annualized rate of VOCs managed at home. VOC subcategories (uncomplicated pain crisis, acute chest syndrome, hepatic and splenic sequestration, and priapism), overall hospitalizations and ER visits and dactylitis events are also assessed. Safety measures include frequency and severity of adverse events. Long-term PK and PD will also be characterized by measuring pre-dose concentrations and percentage of P-selectin inhibition prior to each study drug dose. Part A in each age group will confirm PK dose, beginning with ≥8 pts in G1. If unconfirmed, dose will be adjusted based on population PK model, and ≥8 additional pts enrolled. Once dose is confirmed, recruitment will be expanded for long-term safety and efficacy evaluation of the PK confirmed dose (Part B). This process will then repeat for G2 then G3 (2 to <6 yr). Subsequently, ≥6 G3 pts aged 6 mo to <2 yr will be enrolled, with only pre-dose PK/PD samples collected. Pts on hydroxyurea, L-glutamine or an erythropoietin-stimulating agent must have received the treatment for ≥6 mo prior to screening with no dosage or schedule adjustments during the study. Pts not currently on such drugs must have been off them for ≥6 mo prior to screening. Pts who have received prior crizanlizumab treatment are excluded from the trial. Results: As of January 28, 2020, 59 pts were enrolled: 46 pts in G1 (11 pts in Part A and 35 pts Part B) and 13 pts in G2 Part A. Pt demographics are available for Part A in G1 and 2 (Table), based on 2 Data Monitoring Committee analyses. The median age of G1 was 17.0 yr (range 13-17), 6 (54.5%) were male and 11 (100%) were Black/African American. 9 (81.8%) had HbSS disease, 1 (9.1%) HbSC and 1 (9.1%) HbSβ0. The median age of G2 was 9.0 yr (range 6-11), 8 (61.5%) were male, 7 (53.8%) were Black/African American, 4 (30.8%) were White, and 2 were of multiple race, specifically 'White, Asian' (n=1, 7.7%) and 'White, Black/African American' (n=1, 7.7%). 12 (92.3%) pts had HbSS disease and 1 (7.7%) had HbSC. Conclusions: This study aims to address an unmet treatment need in pediatric pts, exploring appropriate dosing and the safety of crizanlizumab. The annualized rates of VOCs, hospitalizations and ER visits will be assessed as secondary objectives. The primary analyses for Parts A and B of G1 and 2, and then G3, will occur consecutively when all pts enrolled in each group have either completed 26 weeks of treatment or discontinued the study treatment. Disclosures Heeney: UpToDate: Patents & Royalties: Author royalties; Micelle: Consultancy, Other; Keros: Consultancy; Novartis: Consultancy, Other; AstraZeneca: Consultancy, Other; Cyclerion: Consultancy, Other; Forma Therapeutics: Consultancy; Dova: Consultancy; Global Blood Therapeutics: Consultancy; Emerging Therapy Solutions (ETS): Consultancy. Rees:Alnylam Pharmaceuticals: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AstraZeneca: Other: Data monitoring committee membership; Emmanus Medical: Consultancy, Honoraria; TauRx: Other: Data And Safety Monitoring. de Montalembert:Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees. Odame:Novo Nordisk: Other: Study Advisory Board; Global Blood Therapeutics: Other: Study Data Safety Monitoring Board; Novartis: Other: Study Steering Committee. Wali:Novartis: Research Funding. Nguyen:Novartis: Current Employment. Lam:Novartis: Current Employment. Herranz:Novartis: Current Employment. Kanter:NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; bluebird bio, inc: Consultancy, Honoraria; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Guidepoint Global: Honoraria; Cowen: Honoraria; Jeffries: Honoraria; Wells Fargo: Honoraria; Medscape: Honoraria; GLG: Honoraria; Sanofi: Consultancy. OffLabel Disclosure: Crizanlizumab is a monoclonal antibody to P-selectin indicated in the USA for the prevention of vaso-occlusive crises in patients aged 16 years and over with sickle cell disease. This abstract described the new pediatric trial of crizanlizumab, which is not indicated for patients aged less than 16 years of age
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Seigel, Jonathan, David A. Weinstein, Richard Hillman, Brooke Colbert, Belinda Matthews, and Bert Bachrach. "Glycogen Storage Disease Type Ilia Presenting as Non-Ketotic Hypoglycemia: Use of a Newly Approved Commercially Available Mutation Analysis to Non-Invasively Confirm the Diagnosis." Journal of Pediatric Endocrinology and Metabolism 21, no. 6 (June 1, 2008): 587–90. http://dx.doi.org/10.1515/jpem-2008-210613.
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Abstract Glycogen storage disease type III (GSD-111) is an autosomal recessive disorder caused by the lack of amylo-1,6-glucosidase (AGL), one of the catalytic domains of the glycogen debranching enzyme. Deficiency of this enzyme classically results in hepatomegaly and ketotic hypoglycemia. The diagnosis of the disorder was previously confirmed with a liver biopsy demonstrating abnormal liver glycogen content and absent enzyme activity. We describe an 11 month-old African-American Jehovah's Witness male with non-ketotic hypoglycemia (NKH), hepatomegaly, cardiomyopathy, and a flat glucagon response confirmed to have GSD-IIIa by mutation analysis of the A GL gene. The present case represents an unusual presentation (NKH) of GSD-IIIa and emphasizes the utility of the newly approved commercially available Clinical Laboratory Improvement Advisory Committee (CLIA) mutation analysis test.
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Usmani, Saad Z., Vania T. M. Hungria, Xavier Leleu, Hans C. Lee, Faith E. Davies, Caitlin L. Costello, Robert M. Rifkin, et al. "Transplant Status Does Not Impact the Selection of Induction Regimens for Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) in the Insight MM Prospective, Observational Study." Blood 132, Supplement 1 (November 29, 2018): 3289. http://dx.doi.org/10.1182/blood-2018-99-112846.
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Abstract Background The introduction of multiple novel agents and regimens for NDMM and relapsed/refractory MM (RRMM) has improved outcomes while increasing the complexity of treatment selection and disease management. The real-world effectiveness of many novel-agent-based regimens remains to be elucidated. INSIGHT MM (NCT02761187) is the largest global, prospective, observational MM study to date. It aims to understand global NDMM/RRMM disease and pt characteristics, treatment patterns, and clinical outcomes, as well as regional variations. Here we report data for 1056 NDMM pts enrolled from July 1, 2016 to April 27, 2018. Methods INSIGHT MM is enrolling ~4200 adult pts with NDMM/RRMM (1-3 prior therapies) from 15 countries; 9 in Europe (EU), 3 in Latin America (LA), the United States (US), and 2 in Asia. Pts will be followed prospectively for ≥5 yrs. Data are collected from hospital/clinic records at baseline (MM-specific disease characteristics, prior therapies) and every 3 mos (disease management, effectiveness, safety). Results At data cut-off, 1056 NDMM pts had been enrolled from 14 countries, including 495 (47%) from EU, 361 (34%) from the US, 112 (11%) from LA, and 88 (8%) from Taiwan. Median age at enrollment was 64 (range 32-89) yrs and 139 (13%) pts were aged >75 yrs (14%/12%/11%/13% in EU/US/Taiwan/LA); 57% of pts were male (60%/58%/61%/39% in EU/US/Taiwan/LA); 72%, 13%, and 8% were White/Caucasian, Asian, and Black/African American, respectively. Overall, 62% of pts were treated at academic centers and 38% in community settings. Based on accrual at data cut-off, regional differences were observed, with more pts treated at academic centers in EU/Taiwan (88%/91%) vs the US/LA (30%/25%). 87% of pts were treated outside of clinical trials (88%/82%/95%/98% in EU/US/Taiwan/LA). Bone pain (32%, including 33%/28%/40%/37% in EU/US/Taiwan/LA), weakness/fatigue (anemia; 11%, including 12%/10%/6%/18% in EU/US/Taiwan/LA), and kidney problems (5%, including 3%/3%/17%/2% in EU/US/Taiwan/LA) were the most common reasons for pts seeking care; 32% (36%/32%/22%/24% in EU/US/Taiwan/LA) were asymptomatic at diagnosis. At diagnosis, 27%/26%/31% of pts had physician-reported ISS Stage I/II/III MM, and 88% had ECOG PS 0-1; 8% of pts had hypercalcemia, 34% creatinine clearance <60 ml/min, 56% anemia, and 30% >3 bone lesions. The most common reasons for initiating therapy were the presence of CRAB criteria, e.g. bone involvement (54%) and anemia (37%). At start of treatment, fixed-duration therapy, treat-to-best-response, and treat-to-progression approaches were planned for 38%, 29%, and 31% of pts, respectively. The most frequently administered regimens are shown in the Table; 20%/66% of pts received a doublet/triplet. V-based regimens were the most frequently used. Regional differences in regimen selection are emerging: among IMiDs, T is most commonly prescribed in EU, Taiwan, and LA; R is more common in the US. After a median follow-up of 9.3 mos, 72 (7%) pts had discontinued the study, most often due to death (57%), consent withdrawal (14%), or change of treatment provider (11%). At data cut-off, data for 236 (22%) pts who received 1st-line ASCT were available (median age 60 yrs; 12%/63%/25% of pts aged <50/50-65/>65 yrs). Of these, 64% received ASCT at academic centers; 42% of pts each in EU and the US received ASCT vs 11% in Taiwan and 4% in LA. The most frequently administered regimens in ASCT-eligible (n=429) vs ASCT-ineligible (n=571) pts were VC±d (21% vs 21%), VR±d (19% vs 17%) and VT±d (17% vs 10%). At data cut-off, 115 NDMM pts had progressed to 2nd-line therapy; 99 pts received a PI with 1st-line therapy, of whom 33 (33%) then received a PI-based regimen in 2nd line; 61 pts received an IMiD with 1st-line therapy, of whom 35 (57%) then received an IMiD-based regimen in 2nd line. Among 1st/2nd-line pts, 2%/12% received monoclonal antibody therapy. Conclusions PIs and IMiDs remain the global backbones of MM therapy, with V-based regimens most commonly used in NDMM pts, regardless of intended transplant status. These data from INSIGHT MM are beginning to elucidate regional differences in disease presentation and treatment selection, including higher numbers of pts receiving ASCT in the US/EU vs Taiwan/LA, which are likely reflective of differences in healthcare systems and access to MM treatments in the participating countries. Future studies will evaluate the impact of these regional variations on outcomes. Table. Table. Disclosures Usmani: Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy; Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding. Hungria:Celgene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Leleu:Karyopharm: Honoraria; Incyte: Honoraria, Other: steering committee membership ; Celgene: Honoraria, Other: steering committee membership ; Janssen: Honoraria, Other; BMS: Honoraria, Other: steering committee membership ; Merk: Honoraria, Other: steering committee membership ; Takeda: Honoraria, Other: steering committee membership ; Amgen: Honoraria, Other: steering committee membership ; Sanofi: Honoraria, Other: steering committee membership steering committee membership ; Novartis: Honoraria, Other: steering committee membership ; Roche: Honoraria; Gilead: Honoraria. Lee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Davies:Abbvie: Consultancy; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; TRM Oncology: Honoraria; ASH: Honoraria; MMRF: Honoraria. Costello:Poseida Therapeutics, Inc.: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Rifkin:Takeda: Consultancy; EMD Serono: Consultancy; McKesson: Equity Ownership; Celgene: Consultancy; Amgen: Consultancy; Sandoz: Consultancy; Boehringer Ingelheim: Consultancy. Weisel:Amgen, BMS, Celgene, Janssen, and Takeda: Honoraria; Amgen, BMS, Celgene, Janssen, Juno, Sanofi, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene, Janssen, and Sanofi: Research Funding. Chari:Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; The Binding Site: Consultancy; Pharmacyclics: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Puig:Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Celgene: Honoraria, Research Funding. Boccadoro:Amgen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; AbbVie: Honoraria; Mundipharma: Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding. Cook:Bristol-Myers Squibb: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Berdeja:Teva: Research Funding; Janssen: Research Funding; Takeda: Research Funding; Amgen: Research Funding; Poseida Therapeutics, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Bluebird: Research Funding; Genentech: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Sanofi: Research Funding. Zonder:Takeda: Honoraria; Coelum: Honoraria; BMS: Research Funding; Celgene: Consultancy, Honoraria; Alnylam: Honoraria; Janssen: Honoraria; Pharmacyclics: Other: DSMC. Abonour:Prothena: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Hajek:Takeda: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Spencer:Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen-Cilag: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; BMS: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria. Omel:Takeda Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees. Demers:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Romanus:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Ren:Takeda Pharmaceuticals International Co.: Employment. Skacel:Department of Hematology, Charles University General Hospital, Prague, Czech Republic: Other: Affiliation; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Terpos:Novartis: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Genesis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Patents & Royalties; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grant, Research Funding.
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Herr, Megan M., Paul K. Wallace, Yali Zhang, George L. Chen, Sophia R. Balderman, Maureen Ross, Christine Ho, et al. "Age, Sex and Self-Reported Race Differences in Immune Profiles of Hematologic Malignancy Patients." Blood 138, Supplement 1 (November 5, 2021): 4066. http://dx.doi.org/10.1182/blood-2021-150954.
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Abstract INTRO: Immune profiles and immune reconstitution are increasingly studied as important contributors to the prognosis and treatment responses of hematologic malignancy patients. Data on epidemiologic factors influencing immune profiles in hematologic malignancy patients are lacking. METHODS: We performed flow cytometric analyses of immune panels including T-cell, B-cell, NK cell and dendritic cell (DC) subsets in 1,025 consecutive adult hematologic malignancy patients (N=873) and controls/donors (N=152) between 2006-2016. Immune panels were analyzed on fresh peripheral blood samples drawn during workup before autologous or allogeneic hematopoietic cell transplant (HCT). Hematologic malignancy diagnoses were AML (N=235), MM (N=228), NHL (N=197), MDS/MPN (N=85), ALL (N=60), HL (N=33) and other leukemias (N=35). Patients were 58% male, median age 58 years (range 18-77), 91% non-Hispanic white (NHW), 6% African-American (AA), 1.3% Hispanic, 1.5% other. The HCT-comorbidity index (HCT-CI) in patients showed: 63% with > 1 co-morbidity; 26% moderate pulmonary, 22% psychologic (requiring therapy/counseling), 16% severe pulmonary, 12% cardiac (CHF/CAD/MI), 11% diabetes requiring insulin, 9% obese (BMI>35mg/kg 2), 9% prior cancer. Controls were related apheresis or marrow donors of allogeneic HCT patients: 51% male, median age 49 years (range 19-73), 92% NHW, 4% AA, 1.3% Hispanic, 2.6% other. HCT-CI scoring of controls: 45% with > 1 comorbidity, 20% obese, 20% psychologic, 10% mild liver disease, 7% diabetes. Due to inter-individual cell count variability, immune cells were normalized as percent gated of lymphocytes except DC populations which were gated on mononuclear cells, both on forward and side scatter. To control for multiple comparisons, Bonferroni corrected statistically significant P was set at <0.001. RESULTS: In controls, males had a significantly lower proportion of CD3+ cells/µl than females (68% vs 73%, P=0.001), NHW had a higher proportion of CD8+ central memory (CM) cells than other race/ethnicities (4.6 vs 2.7%, P=0.004) with no other significant differences by sex or race, although some of the race groups were low in our cohort. In contrast, among hematologic malignancy patients, males had significantly lower CD4+, CD4+ naïve, CD4+ recent thymic emigrants (RTEs), total T-regulatory cells (Treg), and CD19+ naïve cells but significantly higher CD8+ CM and effector memory (EM) cells than females. In addition, NHW had higher CD8+ CM than AA, Hispanic and Other races. Significant differences by age in patients and controls are shown in the Table. Across all age groups, patients had higher proportions of CD3+ cells, lower proportions of B-cells and no difference in NK or DCs than controls. As controls increased in age, CD4+ total significantly increased, while CD8+total, CD8+naive, T-γδ cells decreased, and myeloid DCs were highest at each end of the age spectrum. As patients increased in age, activated HLA-DR T-cells significantly increased, while T-γδ, CD8+naïve, and RTEs significantly decreased. The CD4:8 ratio increased while the CD4+ and CD8+ naïve:EM ratio decreased with age in both controls and patients, however patients had lower CD4:CD8 and naïve:EM ratios than controls. Immunophenotypes by patient disease are shown in the Figure. In general, patients with lymphoid diseases had lower CD3+CD4+ but higher CD3+CD8+, NK and DCs. In controls/donors, there were no significant differences in immune cell profiles by the presence or absence of comorbidities: obesity, diabetes, psychologic and mild liver disease. In patients, T-γδ were significantly lower in patients with diabetes, with no other significant differences for cardiac, psychologic, prior cancer, obesity or pulmonary co-morbidities. CONCLUSIONS: Additional analyses are ongoing to investigate the influence of prior therapies (chemotherapy, hypomethylating agents, monoclonal antibodies, etc.) and cytogenetic risk groups within each disease (AML, ALL, MDS/MPN, MM, NHL) on immune cell profiles. Studies of immunophenotyping in hematologic malignancies should include adjustment for confounders such as age, sex and race as biologic variables, as well as consideration of the diseases and treatments given. Interestingly, common co-morbidities did not broadly influence immune cell profiles in our cohort of hematologic malignancy patients. Figure 1 Figure 1. Disclosures Chen: Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium. Hillengass: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Beijing Medical Award Foundation: Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Beijing Life Oasis Public Service Center: Speakers Bureau; Skyline: Membership on an entity's Board of Directors or advisory committees; Curio Science: Speakers Bureau; Adaptive: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Axxess Network: Membership on an entity's Board of Directors or advisory committees. Wang: Genentech: Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Other: Advisory Board; Mana Therapeutics: Consultancy, Honoraria; Astellas: 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; Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Advisory board; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy. Griffiths: Takeda Oncology: Consultancy, Honoraria; Alexion Pharmaceuticals: Consultancy, Research Funding; Apellis Pharmaceuticals: Research Funding; Abbvie: Consultancy, Honoraria; Astex Pharmaceuticals: Honoraria, Research Funding; Genentech: Research Funding; Taiho Oncology: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Boston Biomedical: Consultancy. Torka: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees. McCarthy: Bluebird: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Juno: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Pierce, Jennifer Burek, and Erik Henderson. "“We’re So Glad You’re Here, and We’re So Glad You’re Black”: Esther Walls’s Life and Work in Libraries and Literacy Organizations." Libraries: Culture, History, and Society 6, no. 1 (March 1, 2022): 149–69. http://dx.doi.org/10.5325/libraries.6.1.0149.
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ABSTRACT Esther J. Walls (1926–2008) was a Black librarian born in Mason City, Iowa, who sought social justice in her home state before making her belief in equity and literacy the touchstone of her significant career. Walls worked at the New York Public Library and other important institutions, including appointments to prominent organizations’ committees and boards that recognized her deep knowledge and commitment to service. While earning her master’s degree in library science from Columbia University in 1951 and for years afterward, Walls brought Black culture into the Harlem Branch library and brought the library and its resources into the Harlem community, a then-radical act of information-sharing. New technologies and artifacts from her travels to Africa formed the basis for programs and community conversations. In 1963 she led an American Library Association (ALA) Young Adult Services Division (YASD, now YALSA) committee that created African Encounter: A Selected Bibliography of Books, Films, and Other Materials for Promoting an Understanding of Africa Among Young Adults. Her distinguished career included appointments as director of the US Secretariat to promote UNESCO’s International Year of the Book in 1972 and, in the early 1990s, an appointment to the advisory board for the Center for the Book at the Library of Congress.
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Lee, Shawn, Federico Antillón, Deqing Pei, Wenjian Yang, Kathryn G. Roberts, Zhenhua Li, Meenakshi Devidas, et al. "The Impact of Genetic Ancestry on the Biology and Prognosis of Childhood Acute Lymphoblastic Leukemia." Blood 138, Supplement 1 (November 5, 2021): 3476. http://dx.doi.org/10.1182/blood-2021-145655.
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Abstract INTRODUCTION Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Despite improvements in treatment over the past few decades, stark racial disparities persist in disease risk and cure rates. There is a paucity of data describing the genetic basis of these disparities, especially in relation to modern ALL molecular taxonomy and in the context of contemporary treatment regimens. To this end, we sought to determine the associations of genetic ancestry with ALL biology, and the relevance of genetic ancestry to survival outcomes of modern ALL therapy. METHODS This was a multi-national genomic study of 2,428 children with ALL on front-line trials from United States (St Jude Children's Research Hospital and Children's Oncology Group), South-East Asia (Ma-Spore trials) and Latin America (Guatemala), representing diverse populations of European (EUR), African (AFR), Native American (NA), East Asian (EAS), and South Asian (SAS) descent. We performed RNA-sequencing to characterize ALL molecular subtype, and also estimated their genetic ancestral composition by comparing allele frequencies of patient and reference genomes (1000 Genomes Project reference populations). For categorization of patients into racial groups, individuals were classified based on composition of genetic ancestry as: "white" (EUR >90%), "black" (AFR >70%), "Hispanic" (NA >10% and NA greater than AFR), "East Asian" (EAS >90%), "South Asian" (SAS >70%), with the rest defined as "Other". We then evaluated the associations of ancestry with ALL molecular subtypes and survival. RESULTS Genetic ancestral composition of the entire cohort is shown in Figure 1A. Of 21 ALL subtypes, 11 showed significant associations with ancestry. Hyperdiploid ALL was most common in white children (30.6%) and the least frequent in blacks (14.4%) (P<0.001). The frequency of ETV6-RUNX1 was highest in blacks (25.6%) and lowest in Hispanics (10.6%) (P<0.001). The DUX4 subtype was markedly more common in Asian children (14.4% of East Asians and 14.8% of South Asians) compared to black children (1.9%) (P<0.001). There was a similar trend for ZNF384 fusion, representing 6.9% of East Asians, compared to 1.7% for whites (P=0.001). TCF3-PBX1 was most prevalent in blacks at 11.9%, with the lowest at 1.7% in whites (P<0.001). PAX5 alteration frequency was highest in South Asians (11.5%) and lowest in whites (4.5%) (P=0.046). CRLF2 rearrangement occurred significantly more frequently in Hispanics (9.0%) and was least common in blacks (1.3%) (P<0.001). BCR-ABL1-like (excluding CRLF2) was also overrepresented in Hispanic children (11.4%), and occurred less frequently in East Asians (4.2%) (P<0.001). MEF2D fusion was most common in blacks (4.4%), and rare in whites (1.4%) and South Asians (0%) (P=0.013). T-ALL differed dramatically in frequency amongst races, especially between blacks and Hispanics with a 7-fold difference (26.5% vs 3.6%, P<0.001). The pattern of ALL subtype in the "Other" racial category generally mirrored that of the dominant ancestral composition, indicating a strong correlation with ancestry even within admixed populations (Figure 1B). We then examined outcomes across racial/ethnic categories. Event-free survival (EFS), overall survival (OS) and cumulative incidence of any relapse (CIR) all differed significantly across population groups (P=0.017 for EFS, P=0.05 for OS, P=0.015 for relapse). White, East Asian and South Asian children overall had more favorable outcomes compared to their black and Hispanic counterparts. Specifically, Hispanics had the poorest 5-year EFS (72.1 ± 4.2 %) and OS (82.3 ± 3.6 %), whereas South Asians had the highest EFS (94.6 ± 3.6 %) and OS (98.2 ± 2.1 %). Relapse risk trended in parallel with that of EFS and OS, with South Asians having one of the lowest CIR of 3.7 ± 2.6 %, and Hispanics having the highest at 22.8 ± 2.9 %. We repeated the analysis with genetic ancestry as a continuous variable and obtained largely similar results. Importantly, even after adjusting for biological subtypes and clinical features, Native American and African ancestries remained independently associated with poor prognosis. CONCLUSIONS ALL biology and prognosis are highly associated with genetic ancestry, pointing to a genetic basis for racial disparities in ALL. Biology-driven treatment individualization is needed to eliminate racial gaps in the cure of this cancer. Figure 1 Figure 1. Disclosures Evans: Princess Máxima Center for Pediatric Oncology, Scientific Advisory Board, Chair: Membership on an entity's Board of Directors or advisory committees; BioSkryb, Inc.: Membership on an entity's Board of Directors or advisory committees; St. Jude Children's Research Hospital, Emeritus Member (began Jan 2021): Ended employment in the past 24 months. Mullighan: Illumina: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Pfizer: Research Funding; Amgen: Current equity holder in publicly-traded company. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees. Yeoh: Amgen: Honoraria, Other: Chair, Steering Committee for ALL Academy in South East Asia. Pui: Novartis: Other: Data Monitoring Committee; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees.
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Brown, Megan C., Michael H. White, and Robert F. Sidonio. "Obtaining a Von Willebrand Evaluation at Time of Acute Heavy Menstrual Bleeding Presentation Leads to Overestimation of Von Willebrand Levels." Blood 134, Supplement_1 (November 13, 2019): 627. http://dx.doi.org/10.1182/blood-2019-127258.
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Background: Acute heavy menstrual bleeding (HMB) is common for adolescent females, with about a quarter of menstruating females seeking care for HMB over a 3-year time period (O'Brien et al, Blood 2018). Inherited bleeding disorders are common in this adolescent population, identified in 24.6% referred for hematologic evaluation (Zia et al, Blood 2016). The timing and contents of the hemostatic workup for acute HMB in adolescents is extrapolated from adults, although the causes of acute HMB varies significantly between adult women and adolescents. A consensus statement by the American College of Obstetrics and Gynecology recommends obtaining a variety of hemostatic tests including CBC, von Willebrand studies, factor VIII, prothrombin time, partial thromboplastin time, fibrinogen, and thyroid stimulating hormone at the time of presentation (Committee Opinion 557, ACOG 2011). Factor VIII and Von Willebrand studies are known to be increased in the setting of physiologic stress and supplemental estrogen use, questioning their diagnostic accuracy in the setting of acute bleeding. Repeat testing is often required for diagnosis of von Willebrand disease A von Willebrand factor antigen (VWF:Ag) or von Willebrand factor ristocetin cofactor level over 100IU/dL has been shown to have a negative predictive value (NPV) of 95%.(Doshi et al, ASH 2018). Methods: As part of a quality improvement initiative to improve the evaluation and management of adolescents with HMB at Children's Healthcare of Atlanta (CHOA), we instituted an acute HMB protocol for emergency department (ED) and inpatient use. This protocol was implemented at all CHOA emergency departments in metropolitan Atlanta. Subjects were included if they presented with acute HMB as determined by an adapted Philip Menorrhagia Screening Tool. Subjects with a previously diagnosed bleeding disorder, ITP, active rheumatologic disease, cancer, or anticoagulant use were excluded. Descriptive statistics were used to summarize demographics and clinical characteristics. Patients with a positive Philip screen underwent a uniform bleeding inventory and a standardized set of laboratory tests based on the adult consensus statement. Inpatient and outpatient treatments were standardized by hemoglobin level and symptomology. Follow up with hematology and gynecology was encouraged for all. Data was extracted using various heavy menstrual bleeding ICD-10 codes from January 1, 2017 to December 31, 2018. Individuals with von Willebrand studies at baseline and follow up were identified. T-tests and Wilcoxon rank sum tests were utilized to compare VWF:Ag, VWF:RCo and Factor VIII as baseline and follow up. Results: Over a 2-year period, 232 adolescent girls were seen in CHOA EDs for acute HMB with 88 (37.9%) requiring admission and 6 (2.6%) requiring intensive care. The population was primarily African American (63%) with a median age at presentation of 14.8 years (IQR 13.1-16.7). The majority of adolescents had the core hemostatic labs drawn (55.6%) as described per protocol. Thirty-six individuals had baseline and follow up VWD studies. Those with repeat VWD studies were younger (median 13.2 years vs 15.0 years), more commonly white (44.4% vs 21.2%), were more likely to have been admitted (83.3% vs 29.6%) and more likely to have had a hematology follow up appointment (63.4% vs 7.8%). Mean and median VWF:Ag, VWF:RCo and Factor VIII were significantly higher at presentation with HMB than at follow up. Of those with a baseline VWF:Ag and/or VWF:RCo >100, there was a 96.4% NPV for the diagnosis of VWD. For individuals whose initial VWF:Ag and VCWF:RCo were both >100, there was 100% NPV. Conclusions: Among the adolescents cared for at our institution with acute HMB who had confirmatory VWD testing, initial VWF:Ag and VWF:RCo >100 ruled out VWD based on repeat testing. However, poor adherence with hematology or gynecology follow-up may give false reassurance against a diagnosis of VWD. Further improvements of our quality improvement initiative will include a limited hemostatic workup at presentation with a focus on improved adherence to follow up and subsequent hemostatic evaluation. Disclosures White: National Hemophilia Foundation: Other: Shire Clinical Fellowship Program. Sidonio:Kedrion: Research Funding; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees; Uniqure: Membership on an entity's Board of Directors or advisory committees.
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Vij, Ravi, Nitya Nathwani, Thomas G. Martin, Mark A. Fiala, Abhinav Deol, Francis K. Buadi, Jonathan L. Kaufman, et al. "Ixazomib-Lenalidomide-Dexamethasone (IRd) Consolidation Following Autologous Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Large Multi-Center Phase II Trial." Blood 132, Supplement 1 (November 29, 2018): 123. http://dx.doi.org/10.1182/blood-2018-99-109920.
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Abstract Background: Maintenance therapy post-autologous stem cell transplantation (ASCT) has shown to improve progression-free and overall survival in multiple myeloma (MM) and has largely become the standard of care. Consolidation therapy, a brief duration of more-intensive chemotherapy administered prior to maintenance, has been shown to further deepen responses and may improve long-term outcomes. Ixazomib, lenalidomide and dexamethasone (IRd) is an all oral regimen that has been shown to be active in newly diagnosed MM as well as relapsed disease. In this study, we are analyzing the safety and efficacy of IRd as consolidation therapy after ASCT (NCT02253316). Methods: Eligible patients, age 18-70 with newly diagnosed MM undergoing ASCT during first-line treatment, are being consented prior to ASCT. Approximately 4 months following ASCT, patients receive 4 cycles of consolidation therapy with IRd [ixazomib 4 mg on days 1, 8 and 15 of a 28-day cycle, lenalidomide 15 mg on days 1 through 21, and dexamethasone 40 mg on days 1, 8 and 15]. The primary end point is minimal residual disease (MRD) status. MRD is being assessed by ClonoSEQ where possible and by multi-color flow where not. Toxicity, IMWG response rate, PFS, and OS are secondary end points. One month after the last consolidation cycle, patients are randomized (1:1) to maintenance therapy with single-agent ixazomib (4 mg on days 1, 8 and 15) or lenalidomide (15 mg daily). In total, 240 patients will be enrolled on the trial. This presentation coincides with planned interim analysis 2 which included data from the consolidation phase only. Results: As of July 2018, 172 patients with NDMM have been enrolled from 10 centers within the US. The median age was 57 (range 28-70) and 67% were male. 76% were white, 10% African-American/Black, and 13% were another race. 39% were ISS Stage I, 30% were Stage II, and 20% were Stage III. All patients received proteasome inhibitors and/or IMIDs as front-line induction and melphalan as conditioning for ASCT. IRd consolidation started at a median of 110 days post-ASCT (range 80-138). IRd has been well tolerated. Only 4% (6/154) of patients have been unable to complete the 4 cycles of consolidation to date due to toxicity. Grade 3 hematologic toxicity has been uncommon; 4% neutropenia, 3% thrombocytopenia, and 2% anemia. There has been no grade 4 hematologic toxicity. Non-hematologic grade 3-4 toxicities have included: infection (8%), nausea/vomiting/diarrhea (3%), and transaminitis (1%). No grade 3-4 peripheral neuropathy has been reported. One case of grade 5 pneumonia was reported but was not considered related to study treatment. Following ASCT, the MRD-negative rate was 26% and this improved to 37% following consolidation. In the subset of patients with Clonoseq results available, the MRD negative rate improved from 19% to 27%. Clinical response rate improved similarly; prior to consolidation the VGPR or better rate was 76% including 39% CR/sCR. Following consolidation, the VGPR or better rate was 85% including 56% CR/sCR. 137 patients went on to receive maintenance with either ixazomib (n = 71) or lenalidomide (n = 66). At time of submission, the median follow-up from start of IRd is 14 months and 28 patients have relapsed/progressed and 6 have expired. An interim analysis is planned for 2019, representing the first comparison of ixazomib and lenalidomide maintenance. Conclusion: IRd consolidation following ASCT appears to be safe and effective. The all oral regimen is convenient for patients which greatly simplifies follow-up in the peri-transplant period. Study enrollment is scheduled to complete in Q1 of 2019. Disclosures Vij: Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees. Martin:Amgen: Research Funding; Sanofi: Research Funding; Roche: Consultancy. Deol:Kite Pharmaceuticals: Consultancy; Novartis: Consultancy. Kaufman:Janssen: Consultancy; Karyopharm: Other: data monitoring committee; BMS: Consultancy; Abbvie: Consultancy; Roche: Consultancy. Hofmeister:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. Gregory:Poseida Therapeutics, Inc.: Research Funding. Berdeja:Amgen: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda: Research Funding; Poseida Therapeutics, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Bluebird: Research Funding; Genentech: Research Funding; Glenmark: Research Funding; Novartis: Research Funding; Teva: Research Funding; Sanofi: Research Funding. Chari:Pharmacyclics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Array Biopharma: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; The Binding Site: Consultancy.
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Shah, Jatin J., Rafat Abonour, Brian G. M. Durie, Jayesh Mehta, Mohit Narang, Howard Terebelo, Cristina J. Gasparetto, et al. "Connect MM®—the Multiple Myeloma (MM) Disease Registry: Interim Analysis of Overall Survival and Outcomes in Patients with High-Risk Disease." Blood 124, no. 21 (December 6, 2014): 2106. http://dx.doi.org/10.1182/blood.v124.21.2106.2106.
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Abstract Background: MM treatment (Tx) advances have greatly improved clinical outcomes for patients (pts). A recent study demonstrated improved survival in MM through the past decade attributable to the impact of initial therapy with lenalidomide, bortezomib, and thalidomide. The greatest impact was observed in older pts (Kumar, et al. Leukemia, 2014). Connect MM, the first and largest prospective, observational, US-based, multicenter registry was designed to characterize pts, Tx patterns, and outcomes in newly diagnosed MM (NDMM). Methods: This ongoing registry was initiated in September 2009. Eligible pts with NDMM (diagnosis must have occurred within 2 mos of study entry) were enrolled at 234 US sites. Data were collected at baseline and each subsequent quarter using an electronic case report form. The initial enrollment includes all pts who had provided informed consent as of November 1, 2012 (N = 1493). The data cutoff for this analysis was Dec 10, 2013. A total of 1444 pts were treated and were included in overall survival (OS) analyses. Survival was examined for all treated pts adjusting for pt and Tx characteristics including age, autologous stem cell transplant (ASCT) status, gender, race, disease risk factors (International Myeloma Working Group [IMWG] high risk vs. non-high risk), and therapy received (triplet vs. non-triplet) among others. Triplet therapy was defined as any combination of 3 or more drugs during the first Tx regimen. OS was estimated using Kaplan-Meier methods and comparisons across groups were assessed used the log-rank test. Results: At the time of data cutoff, 1493 pts were enrolled with 1444 having received Tx. Of the treated pts 253 pts (18%) had IMWG high-risk disease and 108 pts (7%) had del(17p) at baseline. Median age was 67 y (range, 24-94 y), 57.2% were male, and 81.9% were white. Median follow-up was 29 mos (0-49.4 mos). The median OS for all treated pts was 44.4 mos. When assessed by age group, OS was significantly different (log-rank P < .0001) with a median of 47.6 mos for pts aged < 65 y (n = 632), 45.0 mos for those aged 65 to < 75 y (n = 443), and 33.7 mos for those aged ≥ 75 y (n = 369). OS was significantly longer for pts with ASCT vs. no ASCT (P < .0001), but not different by gender (P = .962) or race (Caucasian vs. African American vs. other; P = .250). Three-year OS probabilities by subgroup are listed in Table 1. When considering risk factors, IMWG risk was borderline significant (high vs. non-high; P = .106), and presence of del(17p) by cytogenetics and FISH was associated with significantly shortened OS (P = .005; Figure 1A). Interestingly, use of triplet therapy vs. non-triplet therapy was associated with significantly prolonged OS regardless of IMWG risk (non-high: P < .0001; high: P = .003; Figure 1B). However, no improvement was noted for triplet vs. non-triplet therapy in pts with del(17p). By multivariate analysis, the significant (P < .05) factors impacting OS were age (in 10-yr increments), International Staging System (ISS) disease stage, ECOG performance status, history of diabetes, anemia, renal function, and platelet count. Conclusions: This interim analysis based on initially treated pts demonstrated that age, ISS stage, and co-morbidities impact OS irrespective of IMWG cytogenetic risk. Triplet Tx was associated with significantly longer OS in pts regardless of IMWG risk status. This is the largest prospective pt cohort with high-risk disease including del(17p). Pts with high-risk disease did not have significantly lower OS vs. pts without high-risk features. Pts with del(17p) (p53 deletion) continue to have shorter OS approaching 3 y and increased survival with use of triplet therapy. Table 1. Kaplan-Meier Estimated 3-Y OS Probability Patients 3-y OS Probability (%) (95% CI) All (N = 1444) 62.6 (59.5-65.8) < 65 y (n = 632) 69.8 (65.2-74.3) 65 to < 75 y (n = 443) 65.0 (59.4-70.6) ≥ 75 y (n = 369) 47.2 (40.7-53.8) Gender Male (n = 831) 62.1 (57.9-66.3) Female (n = 613) 63.4 (58.7-68.2) Race Caucasian (n = 1191) 61.8 (58.3-65.3) African American (n = 183) 64.4 (55.4-73.5) Other (n = 27) 77.6 (57.3-98.0) ASCT Yes (n = 494) 77.1 (72.5-81.7) No (n = 950) 54.2 (50.0-58.3) Triplet therapy Yes (n = 778) 69.3 (65.3-73.3) No (n = 666) 54.8 (49.9-59.6) IMWG risk High (n = 253) 59.0 (51.6-66.4) Standard (n = 566) 66.3 (61.4-71.2) Low (n = 86) 75.7 (63.6-87.8) del(17p) Present (n = 108) 52.7 (41.8-63.6) Absent (n = 1336) 63.4 (60.1-66.7) Figure 1 Figure 1. Disclosures Shah: Celgene Corp: Consultancy, Research Funding. Abonour:Celgene Corp: Honoraria, Speakers Bureau. Durie:Celgene Corp: Export Board Committee Other, Membership on an entity's Board of Directors or advisory committees; IRC Onyx: Membership on an entity's Board of Directors or advisory committees; DMC Millennium: Membership on an entity's Board of Directors or advisory committees; IRC J&J: Membership on an entity's Board of Directors or advisory committees. Mehta:Celgene Corp: Consultancy, Speakers Bureau. Narang:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Thomas:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Hardin:Celgene Corp: Research Funding. Srinivasan:Celgene Corp: Employment, Equity Ownership. Ricafort:Celgene Corp: Employment. Nagarwala:Celgene Corp: Employment. Rifkin:Celgene Corp: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy.
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Rechis, Ruth, Haley Gardiner, Katy Oestman, Stephanie Nutt, and Michael T. Walsh. "Abstract A027: Creating partnerships to deliver community-based interventions for cancer prevention in a historically African American community." Cancer Epidemiology, Biomarkers & Prevention 32, no. 12_Supplement (December 1, 2023): A027. http://dx.doi.org/10.1158/1538-7755.disp23-a027.
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Abstract Be Well Communities™ is MD Anderson’s signature place-based approach for cancer prevention and control, working with communities to promote wellness and address modifiable risk factors for cancer. In this project, the planning phase of the Be Well Communities’ model was implemented in Acres Homes, a neighborhood in northwest Houston with more than 57,000 residents. While the changing demographics show increasing numbers of residents of Hispanic descent (43% of the population), Acres Homes still experiences effects of a legacy of Blacks experiencing poverty; more than half of the population of Acres Homes resides in census tracts that are considered areas of persistent poverty. Further, it is a medically underserved area with relatively high rates of unhealthy behaviors, as compared to Healthy People 2030 goals. To work toward addressing the disparities in health outcomes experienced by community residents, a community advisory group (Steering Committee) including residents, non-profit organizations, health care partners, city and county agencies, plus other stakeholders, was convened and aligned through a structured process to develop shared goals, foster multisector collaboration (as measured by a stakeholder survey administered twice), and enhance community capacity to improve health outcomes through development of a Community Action Plan. Clear, achievable goals were developed, multisector collaboration was enhanced, and more than 400 hours of capacity building support led to a Community Action Plan focused on healthy eating and active living, including 15 evidence-based interventions led by 18 organizations. The majority (93%) of the Steering Committee reports that this plan reflects community priorities and will reach the residents most in need. In the first 2 years of implementation nearly 40% of the residents of the community have been reached by programs including more than 5,000 residents participating in physical activity opportunities, classes and over 1000 individuals receiving outreach from a Community Health Worker within the safety-net hospital system to receive access to healthy food access and nutrition education programming. By listening and developing trust, the Be Well Communities team successfully worked with Acres Homes residents and organizations to enhance community capacity to address health inequities in one of Houston’s most historic communities. Citation Format: Ruth Rechis, Haley Gardiner, Katy Oestman, Stephanie Nutt, Michael T. Walsh Jr.. Creating partnerships to deliver community-based interventions for cancer prevention in a historically African American community [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A027.
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Ip, Andrew, Michael C. Churnetski, Oscar Calzada, Andres Chang, Yuan Liu, Nassoma Bumpers, Deborah Leeson, et al. "The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a Feasibility Study." Blood 132, Supplement 1 (November 29, 2018): 5911. http://dx.doi.org/10.1182/blood-2018-99-119757.
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Abstract Background: Based on cohort studies and a limited number of prospective studies, physical activity (PA) can improve quality of life (QoL) in non-Hodgkin lymphoma (NHL), multiple myeloma (MM), and patients (pts) undergoing autologous stem cell transplant (ASCT). There are also data to suggest that survival (Pophali et al, ASH 2017) is improved with increased PA in NHL pts. After ASCT, it is known that QoL and physical function will decrease. PA has been linked to improved QoL outcomes for pts undergoing ASCT. Recently, evidence shows fitness trackers can help monitor and improve adherence to PA in cancer pts. We aim to study the feasibility of a PA intervention in NHL/MM patients undergoing ASCT and to assess the use of smart watches in this setting to monitor PA. Methods: We included MM and NHL pts undergoing ASCT. Key inclusion criteria included ECOG < 2 and ability to complete a 6 minute walk test (6MWT). Pts were asked to adhere to a PA program of 150 minutes a week on a stationary bicycle or by walking, recording data in a diary and by wearing a smart watch provided to them. Data were collected from date of hospitalization to discharge, with research staff checking on pts at least twice a week to ensure adequate data collection and adherence. Feasibility of the intervention was assessed by average weekly minutes of PA performed by self-report. Validation of moderate intensity PA was attempted by heart rate (HR) monitoring (goal 40% of HR reserve) by the smart watch. QoL was assessed from FACT-lymphoma and FACT-MM surveys prior to transplant and around day 30 post ASCT. Clinical outcomes measured include time to neutrophil engraftment (≥0.5 10E3/mcL) and physical function (6MWT). Survey scores and 6MWT distances were compared using Wilcoxson rank sum tests. Historical controls at Emory matched for age, disease status, conditioning, stem cells infused, and use of stimulating factor were used to compare median time to neutrophil engraftment. Results: Since April 2018, 10 pts have enrolled and completed the PA intervention. Median age was 62, 70% were males, 40% had NHL, 50% were African American, and 50% were Caucasian. All pts were chemotherapy sensitive at time of transplant. Conditioning regimens included BEAM (30%), Melphalan (60%) and Busulfan/cyclophosphamide/etoposide (10%). Granulocyte colony stimulating factor was used in 60% of pts. Median follow up was 22 days. Six of 9 (67%) patients were able to adhere to a PA regimen while hospitalized by self-report, with one patient having incomplete PA data. Eight of ten patients wore their watch regularly for HR analysis. Six of these eight patients (75%) consistently reached HR goal during their PA. Of the 6 patients who met PA goal by self-report, 4 (67%) consistently met HR goals during PA (sample data, figure 1). QoL scores measured by FACT-lymphoma and FACT-MM showed no significant decrease in total score from pre-intervention to post-discharge follow up (median score difference -2.5 points, p-value=0.72, table 1). Individual sections of FACT surveys showed no significant differences except emotional well-being (median score difference, -3 points, p=0.008, table 1). Physical function by 6MWT decreased by a median of 97 meters (pre-test median of 435 meters, post-test median of 333.5 meters, p-value=0.016, table 1). Compared to 20 historical controls, median time to engraftment was similar (12 days vs 12.5 days). Conclusion: Our findings support the feasibility of studying an inpatient PA intervention for ASCT pts using traditional and novel methods. Nearly 70% of pts who participated were successful in adhering to a PA regimen of 150 minutes of exercise. Ongoing assessment by research staff to encourage pts to adhere to prescribed exercise, as well as use of a smart watch to validate PA by HR data was feasible. QoL results are consistent with prior PA studies in ASCT pts, with no significant decrease in overall QoL by day +30. Additional analyses from this study, including a flow-based panel to measure the impact of PA on immune reconstitution post ASCT, will be presented at the meeting. We plan to utilize the findings from this feasibility study to construct a randomized study of PA in ASCT assessing QoL as a primary outcome. Disclosures Calzada: Seattle Genetics: Research Funding. Nooka:Janssen pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive technologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Spectrum Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hofmeister:Bristol-Myers Squibb: Research Funding; Adaptive biotechnologies: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Allen:Merck: Research Funding; Bayer: Consultancy. Kaufman:Karyopharm: Other: data monitoring committee; Abbvie: Consultancy; Janssen: Consultancy; BMS: Consultancy; Roche: Consultancy. Blum:Morphosys: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Lonial:Amgen: Research Funding. Waller:Cambium Medical Technologies: Consultancy, Equity Ownership; Pharmacyclics: Other: Travel Expenses, EHA, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celldex: Research Funding; Kalytera: Consultancy. Flowers:Celgene: Research Funding; Millennium/Takeda: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Pharmacyclics/ Janssen: Consultancy; Eastern Cooperative Oncology Group: Research Funding; V Foundation: Research Funding; Denovo Biopharma: Consultancy; Spectrum: Consultancy; Abbvie: Consultancy, Research Funding; OptumRx: Consultancy; Abbvie: Research Funding; Gilead: Research Funding; Karyopharm: Consultancy; BeiGene: Research Funding; Bayer: Consultancy; Janssen Pharmaceutical: Research Funding; Gilead: Consultancy; Genentech/Roche: Research Funding; Pharmacyclics: Research Funding; National Cancer Institute: Research Funding; Burroughs Wellcome Fund: Research Funding; Genentech/Roche: Consultancy. Cohen:Bristol-Myers Squibb: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioInvent: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Infinity Pharmaceuticals: 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; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioInvent: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding.
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Heeney, Matthew M., David C. Rees, Mariane De Montalembert, Isaac Odame, R. Clark Clark Brown, Yasser Wali, Thu Thuy Nguyen, Du Lam, Nadege Pfender, and Julie Kanter. "Initial Safety and Efficacy Results from the Phase II, Multicenter, Open-Label Solace-Kids Trial of Crizanlizumab in Adolescents with Sickle Cell Disease (SCD)." Blood 138, Supplement 1 (November 5, 2021): 12. http://dx.doi.org/10.1182/blood-2021-144730.
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Abstract Background: Vaso-occlusive crises (VOCs) are the hallmark of SCD. The cell adhesion molecule P-selectin plays a key role in the multicellular interactions that can lead to VOCs. In the SUSTAIN trial in adults, crizanlizumab 5.0 mg/kg, a humanized monoclonal antibody that blocks P-selectin, significantly reduced the median annualized rate of VOCs vs placebo and had a favorable safety profile (Ataga et al. N Engl J Med 2017). Aim: To describe initial safety and efficacy results for patients (pts) with SCD aged 12-<18 yr treated with crizanlizumab 5.0 mg/kg, with or without hydroxyurea (HU), in the SOLACE-kids trial (ClinicalTrials.gov NCT03474965). Methods: SOLACE-kids is a Phase II study to confirm and establish appropriate dosing and evaluate safety of crizanlizumab in pediatric pts with SCD (any genotype) and ≥1 VOC leading to a healthcare (HC) visit within 12 mo prior to screening. Pts (N≥100) are stratified by age: Group 1 (G1; 12-<18 yr), Group 2 (6-<12 yr) and Group 3 (6 mo-<6 yr). Part A of the trial will confirm and establish crizanlizumab dosing based on first-dose and multiple-dose pharmacokinetic (PK) results (targeting similar exposure to adults) and safety in each group; Part B will expand recruitment for pts and evaluate long-term safety and efficacy of the PK-confirmed dose. Crizanlizumab is administered on Day 1, Day 15, then every 4 wk (up to 2 yr). Primary endpoints are PK and pharmacodynamic parameters (after starting dose and multiple doses) and frequency of adverse events (AEs). Secondary endpoints include the annualized rate of VOCs leading to HC visit, annualized rate of hospitalizations/emergency room (ER) visits and additional safety measures. This analysis focuses on safety and efficacy data of G1 pts receiving crizanlizumab 5 mg/kg. Results: As of 28 August 2020, 50 pts were enrolled in G1 of SOLACE-kids. Mean (SD) age of pts was 15.0 (1.92) yr, 29 (58%) were female, 44 (88%) had the HbSS genotype, 32 (64%) were Black/African American and 42 (84%) were receiving HU. Median (range) duration of exposure to crizanlizumab was 36.6 (6-98) wk; 44 (88%) pts received treatment for ≥26 wk. The most commonly reported AEs were headache (n=14 [28%]), vomiting (n=12 [24%]) and back pain (n=9 [18%]). Grade ≥3 AEs were reported in 13 (26%) pts; most common were anemia (n=3 [6%]) and back pain (n=2 [4%]). Serious AEs were reported in 11 (22%) pts; none were deemed related to treatment. Incidence of AEs of special interest (AESI) is shown in Table 1. No AESI led to treatment discontinuation except 1 pt who died of meningitis (not related to treatment). No infusion-related reactions were serious; all had resolved at data cut-off (except for 1 case of Grade 1 dizziness). No case of anaphylactic reaction to crizanlizumab was reported. Pain events on the day of crizanlizumab infusion suspected to be related to treatment were reported in 3 (6%) pts. All pain events, regardless of relationship to treatment, were Grade 1/2, except for two Grade 3 events reported in the same pt (back pain and pain in extremity), which resolved on day of onset. All hemorrhage events were mild and not considered related to treatment. Increase from baseline (BL) in total bilirubin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was reported in 29 (58%), 17 (34%) and 20 (40%) pts, respectively. 2 (4%) pts had Grade 4 total bilirubin significantly above normal (1 pt was Grade 4 and 1 pt was Grade 3 at BL); 21 (42%) pts had Grade 3 total bilirubin significantly above normal (5 pts were Grade 3 at BL). Grade 3 increase in ALT and AST was reported in 2 (4%) pts each. All reported liver function parameters did not meet study criteria for severe drug-induced liver injury. The median (range) number of VOCs leading to a HC visit was 3.0 (1.0-26.0) at BL and 1.6 (0.0-12.7) on treatment (median absolute reduction: 1.0 [range: -13.3 to 5.8]). 18 (36%) pts did not experience a VOC leading to a HC visit while on treatment. The median (range) annualized rate of hospitalizations/ER visits at BL was 4.0 (1.0-36.0) vs 1.54 (0.0-14.3) on treatment (median reduction: 2.35 [range: -21.7 to 5.3]) (Table 2). Conclusion: This initial analysis of SOLACE-kids shows crizanlizumab 5.0 mg/kg is safe and well tolerated in pts aged 12-<18 yr, consistent with the established profile of crizanlizumab in adult pts. No new safety signals were identified. Compared with BL, crizanlizumab 5.0 mg/kg treatment led to a median reduction of 1 VOC leading to a HC visit/year in this pt population. Figure 1 Figure 1. Disclosures Heeney: FORMA: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Vertex / Crispr Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; bluebird bio: Consultancy; Keros: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Cyclerion: 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, Research Funding. Rees: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Addmedica: Honoraria; TauRx: Membership on an entity's Board of Directors or advisory committees. De Montalembert: Vertex: Membership on an entity's Board of Directors or advisory committees; bluebird bio: Membership on an entity's Board of Directors or advisory committees; Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Odame: Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Steering Committee; Global Blood Therapeutics: Other: DSMB. Brown: Imara: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Novo Nordisk: Consultancy; Forma Therapeutics: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Wali: Novatis Oncology: Research Funding. Nguyen: Novartis: Current Employment. Lam: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Pfender: Novartis: Current Employment, Current equity holder in publicly-traded company. Kanter: Fulcrum Therapeutics, Inc.: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Forma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beam: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Graphite Bio: Consultancy; GuidePoint Global: Honoraria; Fulcrum Tx: Consultancy.
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Sood, Suman L., Dunlei Cheng, Amy D. Shapiro, Craig M. Kessler, Nigel S. Key, Doris V. Quon, M. Elaine Eyster, et al. "A Cross-Sectional Analysis of Cardiovascular Disease in the Hemophilia Population." Blood 124, no. 21 (December 6, 2014): 2836. http://dx.doi.org/10.1182/blood.v124.21.2836.2836.
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Abstract Introduction: Cardiovascular disease (CVD) is a disease of aging. While men with hemophilia were initially thought to be protected from CVD, it is now clear that atherothrombotic events do occur. The objective of this study is to determine the prevalence of CVD and CV risk factors among older men with moderate and severe hemophilia. Methods: A U.S. national cross-sectional study began enrollment in 10/2012. Inclusion criteria are men with moderate or severe congenital hemophilia A or B (FVIII or IX level ≤ 5%), age 54-73. Men with an additional bleeding disorder (besides liver dysfunction) were excluded. After obtaining informed consent, CV risk factors, medications, and history of thrombotic events were obtained from patient interview and chart review. A fasting blood sample was assayed centrally. Results: As of 8/1/2014, 160/200 planned subjects were recruited and interim analysis on 126 subjects from 18 U.S. Hemophilia Treatment Centers is presented here. The majority were white (109; 86.9%) or African American (15; 11.5%). Mean age was 62 years (SD: 5; range: 54-74). Most used factor on demand, with only 34.1% (43/126) on prophylaxis, defined as ≥2 doses of FVIII or ≥ 1 dose FIX/week. Five (4.0%) had a current inhibitor. Viral infection was common; 68.3% currently had hepatitis C, and 25% HIV. Hypertension (HTN) was reported in 65.6% of subjects, 37.3% dyslipidemia and 24.6% diabetes (DM); 44.5% had ever smoked, 56.3% denied engaging in at least moderate physical activity and 43.7% had a family history of CVD. Average BMI was 28 kg/m2 (29.4% obese) and waist circumference 97 cm. Fasting blood work showed an abnormally elevated: creatinine in 27.6% subjects (mean 1.09 mg/dl, SD 0.5), CRP in 6.3% (4.15 mg/L, 10.6), total cholesterol in 18.1% (169.49 mg/dl, 35.8), triglycerides in 25.2% (122.10 mg/dl, 58.2), LDL in 19.7% (102.27 mg/dl, 32.3); and low HDL in 45.7% (42.80 mg/dl, 12.2). Ten subjects (7.9%) reported prior angina; 7 (5.6%) atrial fibrillation/flutter; 3 (2.4%) leg deep venous thrombosis; 2 (1.6%) myocardial infarction (MI), transient ischemic event (TIA), or pulmonary emboli; and 1 (0.8%) coronary artery angioplasty, stent placement, CABG, or peripheral arterial angioplasty. In total, 11 subjects had CVD (defined as angina, MI, TIA, or ischemic or embolic stroke), a prevalence rate of 8.7%. This is significantly lower than the reported prevalence of 23% CVD in similar aged men without hemophilia in the longitudinal ARIC cohort (p-value <0.001). The qualifying diagnoses in our cohort included angina, MI and TIA. None of the men with CVD were on antiplatelet or anticoagulant medications. Due to the small number of events, individual CV risk factors thus far did not achieve statistical significance in predicting CVD. Compared to never smokers, ever smokers had an odds ratio (OR) of 3.7 (95% CI: 0.9-14.8) of CVD. For HTN, dyslipidemia, and DM, the OR (95% CI) of CVD were 2.5 (0.5-12.1), 2.2 (0.6-7.5), and 1.9 (0.5-6.8), respectively. Positive family history (OR 2.4 (0.7-8.8)) and low-level of physical activity (1.4 (0.4-5.0)) also suggested some association with increased CVD risk. Obese BMI and large waist circumference were not significant. Men using prophylaxis appeared less likely to have CVD (1/43, 2.3%) than men not on prophylaxis (10/83, 12.1%), OR 0.2 (0.02-1.4), although the difference was not statistically significant. HIV+ men (1/32, 3.1%) were also less likely to have CVD compared to non-HIV+ men (10/92, 10.9%), OR 0.3 (0.2-10.9), but not significantly so. Lastly we investigated the role of anti-HTN (used in 36.5% of all subjects), cholesterol lowering (16.7%), and DM medications (10.3%) in reducing CVD. Not taking anti-HTN, cholesterol or DM medications non-significantly increased CVD risk with an OR in all subjects of 1.5, 3.3, or 3.9 respectively. Conclusions: In this interim analysis of an ongoing national cross-sectional study, older men with moderate to severe hemophilia commonly report risk factors for CVD, including HTN (65.6%), dyslipidemia (37.3%) and renal insufficiency (27.6%). Despite this, the prevalence of reported CVD is low at 8.7%, suggesting that men with hemophilia may be protected from forming pathogenic thrombi. More data is needed to determine if the approach to prophylaxis or other therapies should be altered in this population. We plan to formally compare the prevalence of CVD and CV risk factors with similarly aged men in the ARIC database once enrollment is complete. Disclosures Sood: Bayer: Research Funding. Shapiro:Baxter: Consultancy, Global Steering Committee Other, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Consultancy, Global Steering Committee, Global Steering Committee Other, Research Funding; CSL Behring: Research Funding; Biogen Idec: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kempton:Baxter Healthcare, Inc: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Kedrion Biopharma: Membership on an entity's Board of Directors or advisory committees; NovoNordisk, Inc: Research Funding. Fogarty:Amgen Inc: Consultancy; Bayer HealthCare Pharmaceuticals: Consultancy; Baxter: Consultancy; Biogen Idec Inc.: Consultancy; Chugai Pharma USA: Consultancy; Pfizer Inc: Consultancy; Baxter: Research Funding; Biogen Idec Inc.: Research Funding; CSL Behring: Research Funding; Pfizer Inc: Research Funding; Medscape LLC: Honoraria; VindicoMed: Honoraria. Ragni:Biogen Idec: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Tacere Benitec: Consultancy, Drug Safety Monitoring Board, Drug Safety Monitoring Board Other; Baxter: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Merck: Research Funding; Novartis: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Spark Therapeutics: Research Funding; Vascular Medicine Institute, PIttsburgh, PA: Research Funding. Neff:Baxter: Membership on an entity's Board of Directors or advisory committees. Konkle:CDC: Research Funding, This work was supported by CDC grant 1U01DD000761-01 Other.
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McSweeney, Jean, David Robinson, Anthony McGuire, Pamela Christie, Sandra Hatley, Martha Rojo, and Laura James. "2025." Journal of Clinical and Translational Science 1, S1 (September 2017): 67–68. http://dx.doi.org/10.1017/cts.2017.240.
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OBJECTIVES/SPECIFIC AIMS: To establish a state-wide research registry of diverse participants. METHODS/STUDY POPULATION: We garnered broad institutional and community support by involving TRI’s Community Engagement team, its Community Advisory Board (CAB), and 3 UAMS patient CABs in selecting Web site content, images, and colors. Using this feedback, the TRI Recruitment Unit (RU), in conjunction with UAMS Communications and the Center for Health Literacy, developed the materials and crafted comprehensive communication and recruitment strategies. The UAMS Center for Pacific Islander Health, Hispanic faculty, and CAB members translated materials. UAMS IT programmed the user-friendly site to allow registration from smartphones and i-Pads and linked to UAMS patient electronic health messages. RESULTS/ANTICIPATED RESULTS: The RU committee implemented successful innovative strategies, including recruiting at the Arkansas State Fair and ballgames, attended by people of all races, ages, and socio-economic levels. Using i-Pads at the sites, recruitment took <5 minutes/registrant. Within 8 months, >2400 participants from across Arkansas had joined the registry: 14% African-Americans, 8% Pacific Islanders, 5% Hispanic, and 3% Native American. DISCUSSION/SIGNIFICANCE OF IMPACT: Involving CAB multidisciplinary input to design and implement recruitment materials was highly successful. Despite challenges of recruiting under-represented groups, the registry includes 30% minorities. By tracking registrants’ demographics with Lime Survey software, the RU will prioritize future recruitment events to maximize diversity of registrants.
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Hood, Anna M., Heather Strong, Cara Nwankwo, Yolanda Johnson, Constance A. Mara, Lisa M. Shook, William Brinkman, et al. "Addressing Recruitment Challenges in the Engage-HU Trial in Young Children with Sickle Cell Disease." Blood 136, Supplement 1 (November 5, 2020): 26–27. http://dx.doi.org/10.1182/blood-2020-141471.
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Background: Sickle cell disease (SCD) is a genetic disorder that causes significant medical and neurologic morbidity in children. Hydroxyurea (HU) is the primary medication used to prevent these complications. National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend offering HU to children as young as 9 months of age with SCD (HbSS or HbSB0 thalassemia) using a shared decision-making approach. Although HU has proven efficacious it remains underutilized and caregivers report that they are not always actively involved in the decision to initiate this therapy. Reasons for limited HU uptake likely include lack of clinician knowledge and training and negative caregiver perceptions. Thus, we developed the Engage-HU trial as a novel approach to address HU utilization barriers. A critical consideration for this trial was that SCD primarily affects individuals of African and Hispanic/Latino descent. In these minority populations, intervention trials are sometimes terminated early because of recruitment difficulties related to mistrust of research, caregiver burden, and transportation issues. As such, the Engage-HU trial design included best-practice strategies for recruiting people of color in research. This study describes these strategies, the initial recruitment plan, preliminary recruitment outcomes and strategies, and our procedural adaptations. Study Design and Methods: Engage-HU is a randomized control trial (NCT03442114) to assess how clinicians can engage caregivers in a shared discussion that considers their values and preferences and includes evidence that supports HU. Engage-HU compares two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD: 1) the American Society of Hematology Pocket Guide, and 2) the HU Shared-Decision Making (H-SDM) Toolkit. The study aims to recruit 174 caregivers and evaluate the effectiveness of the dissemination methods on patient-centered outcomes (caregiver confidence in decision-making and perceptions of experiencing shared decision-making) as well as HU uptake and child health outcomes. Eligible children are aged 0 to 5 years, candidates for HU, and their caregiver has not made a decision about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a stepped-wedge design. Data will be analyzed based on the intent-to-treat principle. All participants will remain in the arm of the study to which they were randomized, regardless of whether or not they receive the assigned dissemination method. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using a linear mixed effects regression model with a robust variance estimator and maximum likelihood estimation with observations clustered within site. The Engage-HU trial includes adaptations to increase recruitment such as tailored messaging, a relational recruitment approach, streamlined data collection, and a Stakeholder Advisory Committee. However, even with these adaptations, the first 6-months of the trial yielded lower than anticipated recruitment. Rather than terminate the trial or accept low enrollment, the research team implemented a series of recruitment strategies to address barriers including helping to improve research coordinator knowledge of the study purpose and adjusting no-show and follow-up procedures (e.g., calls to families after missed appointments and reminder calls before appointments). Site clinicians and clinic staff were provided with additional training so they could give more context about Engage-HU to caregivers and the study principal investigator led monthly "all coordinator" calls to provide support by sharing updates and experiences about successful recruitment. Implementation of these strategies resulted in triple the number of enrollments over the next 7-months compared to the previous 6-months (Table 1). Our goal in sharing this information is to provide lessons learned that can be implemented in future trials with the systematically underserved SCD population. It is also anticipated that methods described here may also inform clinical approaches to better engage caregivers of young children around critical clinical conversations, such as initiating medications like HU. Disclosures King: Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; RiverVest: Consultancy; Novimmune: Research Funding; Celgene: Consultancy; Tioma Therapuetics: Consultancy; Amphivena Therapeutics: Research Funding; WUGEN: Current equity holder in private company; Cell Works: Consultancy; Incyte: Consultancy. Smith-Whitley:Prime: Other: Education material; Celgene: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Neumayr:Emmaus: Consultancy; Bayer: Consultancy; CTD Holdings: Consultancy; Pfizer: Consultancy; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Micelle: Other: Site principal investigator; GBT: Other: Site principal investigator; PCORI: Other: site principal investigator; Novartis: Other: co-investigator; Bluebird Bio: Other: co-investigator; Sangamo Therapeutics: Other; Silarus: Other; Celgene: Other; La Jolla Pharmaceuticals: Other; Forma: Other; Imara: Other; National Heart, Lung, and Blood Institute: Other; Health Resources and Services Administration: Other; Centers for Disease Control and Prevention: Other; Seattle Children's Research: Other. Yates:Novartis: Research Funding. Thompson:Novartis: Consultancy, Honoraria, Research Funding; CRISPR/Vertex: Research Funding; BMS: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; bluebird bio, Inc.: Consultancy, Research Funding.
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Vasquez, Kimberly S., Adam Qureshi, Andrea Ronning, Moufdi Naji, Cameron Coffran, Clewert Sylvester, Glenis George-Alexander, et al. "58096 A community-academic partnership to implement DASH diet and social/behavioral interventions in congregate meal settings to reduce hypertension among seniors aging in place." Journal of Clinical and Translational Science 5, s1 (March 2021): 76. http://dx.doi.org/10.1017/cts.2021.598.
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ABSTRACT IMPACT: Our implementation model translates two evidence-based nutritional and behavioral interventions to lower blood pressure, into a community-based intervention program for seniors receiving congregate meals. OBJECTIVES/GOALS: The Rockefeller University, Clinical Directors Network, and Carter Burden Network received an Administration for Community Living Nutrition Innovation grant to test whether implementation of DASH-concordant meals and health education programs together lower blood pressure among seniors aging in place. METHODS/STUDY POPULATION: n=200, >60 yr, >4 meals/week at CBN; engagement of seniors/stakeholders in planning and conduct; Advisory Committee to facilitate dissemination; menus aligned with Dietary Approaches to Stop Hypertension (DASH) and NYC Department for the Aging nutritional guidelines; interactive sessions for education in nutrition, BP management, medication adherence. Training in use of automated daily home BP monitors (Omron 20). Validated surveys at M0, M1, M3, M6. Taste preference and cost assessed through Meal Satisfaction (Likert scale) and Plate Waste measures. Primary Outcome: Change in Systolic BP (SBP) at Month 1; change in %BP controlled. Secondary: validated cognitive, behavioral, nutritional measures (SF-12, PQH-2), economics; staff/client satisfaction, trends and significant associations. RESULTS/ANTICIPATED RESULTS: n=94, x2 age =73 +/- 8 years, 65% female, 50% White, 32% Black/African American, 4% Asian, 1% American Indian, Alaskan Native, 13% Other, 32% Latino/a, 43% with income <$20,000. Mean SBP at Baseline was 137.87 +18.8 mmHg (range 98-191). Menus were adapted to provide 20% daily DASH requirements at breakfast, 50% at lunch. Participants attended classes in nutrition and medication management and were provided with and trained to use an automated home BP monitor. Meal satisfaction scores dipped briefly then met or exceed pre-DASH levels. Home BP data was downloaded every 2-4 weeks with social/behavioral support. The COVID-19 closures interfered with BP outcome data collection and meal service ceased. Primary outcome: x2 change in SBP at Month 1 = -4.41 mmHg + 18 (n=61) (p=0.713). Significant associations will be reported. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our community-academic research partnership implemented the DASH diet in congregate-meal settings to address uncontrolled hypertension in seniors. COVID-19 interrupted the study, but encouraging trends were observed that may inform refinement to this community-based health intervention for seniors.
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Visram, Alissa, Eli Muchtar, S. Vincent Rajkumar, Celine M. Vachon, Angela Dispenzieri, Prashant Kapoor, Martha Q. Lacy, et al. "Prevalence of Familial Plasma Cell Disorders in Patients with Multiple Myeloma." Blood 136, Supplement 1 (November 5, 2020): 1–2. http://dx.doi.org/10.1182/blood-2020-143098.
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Introduction: First degree relatives of patients with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM), and African Americans, have an increased risk of having MGUS and MM compared to the general population. However, current guidelines do not advocate for screening family members of MM for plasma cell disorders (PCD). Understanding the epidemiology of familial plasma cell disorders (PCDs) is essential in order to identify people at highest risk of developing PCDs who may benefit from targeted screening strategies. The aims of this study were to assess the prevalence of MM patients with a family history of PCD, and the implications of a family history of PCD on the overall survival (OS) of MM patients. Methods: We retrospectively reviewed the electronic medical records of patients with symptomatic MM followed at Mayo Clinic and diagnosed between January 1989 and June 2019. Clinical notes were reviewed for documentation pertaining to family history of PCDs. Kaplan Meier survival analysis was used to assess the OS, where OS was calculated from the date of diagnosis of symptomatic MM until death; patients were censored if they were alive at the date of last follow up. A Cox proportional hazards model was used to provide risk estimates for OS. Results: A total of 8403 patients with symptomatic MM were included in this study. Family history was documented in 1521 patients, and 291 patients (3.5% of all patients, 19% of those with any documented family history) had a documented family member with a PCD. The median age at diagnosis of symptomatic MM was significantly lower in patients with (n=291) versus without (n= 8112) a family history of PCD (60.9 versus 63.6 years, p<0.0001). The median OS of MM patients with a family history of PCD was significantly longer than MM patients without a family history of PCD (8.1 versus 4.9 years, respectively, with p<0.0001, see figure 1). Using a multivariable Cox proportional hazards model, MM patients with a family history of PCD had a significantly lower risk of death compared to those without a family history of PCD (HR 0.66, 95% CI 0.55-0.78, p<0.0001) even after adjusting for sex, age at diagnosis (above versus below age 65), self-reported race (African American versus not African American), or date of diagnosis (before versus after 2010). When restricting the analyses to the 1521 patients with clearly documented family history, the survival benefit amongst patients with versus without a family history of PCD was similar. In probands with a PCD family history, 182 (63%) had a first degree relative with PCD, whereas 109 (37%) had a second degree relative with PCD. The most common reported PCD amongst family members was MM (figure 2). Nineteen (6.5%) probands with a family history of PCD had 2 or more relatives with a PCD (6 MM patients had 2 or more first degree relatives, 5 MM patients had at least 1 first and 1 second degree relative, and 8 MM patients had 2 or more second degree relatives with a PCD history). There was no significant difference in the median OS between MM patients with a first degree versus second degree relative with PCD (HR 1.03, 95% CI 0.74-1.46, p=0.837), or MM patients with 1 versus 2 or more relatives with PCD (HR 1.01, 95% CI 0.53-1.96, p=0.962). Conclusion: We reviewed patients with symptomatic MM seen at Mayo Clinic over the last 30 years and found that the prevalence of patients with a documented family history of PCD was 3.5%. MM patients with a family history of PCD were diagnosed with MM at a younger age and survived longer than patients without a family history of PCD. Further work is needed to understand factors underlying the survival benefit in patients with a family history of PCD, and whether they present with less aggressive or less advanced disease at diagnosis. Disclosures Dispenzieri: Intellia: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Kapoor:Sanofi: Consultancy, Research Funding; Cellectar: Consultancy; Janssen: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Celgene: Honoraria. Gertz:Spectrum: Other: personal fee, Research Funding; Janssen: Other: personal fee; Abbvie: Other; Amgen: Other: personal fee; Physicians Education Resource: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Prothena: Other: personal fee; Teva: Speakers Bureau; Celgene: Other; Research to Practice: Other; Sanofi: Other; DAVA oncology: Speakers Bureau; Annexon: Other: personal fee; Appellis: Other: personal fee; Ionis/Akcea: Other: personal fee; Alnylam: Other: personal fee; Aurora Bio: Other; Proclara: Other; Johnson and Johnson: Speakers Bureau; Springer Publishing: Patents & Royalties. Kumar:Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Novartis: Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Carsgen: Other, Research Funding; Cellectar: Other; Dr. Reddy's Laboratories: Honoraria; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; BMS: Consultancy, Research Funding; Karyopharm: Consultancy; MedImmune: Research Funding; Sanofi: Research Funding; Tenebio: Other, Research Funding; Kite Pharma: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Genecentrix: Consultancy; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments.
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Fiala, Mark A., Tanya M. Wildes, Mark A. Schroeder, Armin Ghobadi, Keith E. Stockerl-Goldstein, and Ravi Vij. "Disparities in Healthcare Resource Utilization for Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 4793. http://dx.doi.org/10.1182/blood-2018-99-118392.
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Abstract Background: Nearly half of older African-Americans who develop multiple myeloma (MM) do not receive systemic treatment. Those who do are less likely to receive newer treatments, such as novel agents and stem cell transplant, than their peers. In this study, we sought to determine if disparities in resource utilization exist even among patients receiving similar treatment. Methods: All newly diagnosed MM cases from 2007-2013 in the SEER-Medicare dataset were reviewed along with their corresponding claims data through 2014. We excluded cases 1) not enrolled in Medicare Part A, B, and D; 2) HMO enrollees; 3) those diagnosed prior to age 65; 4) all patients who did not receive a proteasome inhibitor and/or an immunomodulatory drug within 6 months; 5) those who underwent stem cell mobilization or transplantation; or 6) died within 12 months of MM diagnosis. All reported medical costs including both those paid by Medicare and patient copays for the first 12 months post-diagnosis were captured and adjusted for inflation. Results: 2,841 patients were included. The median age was 74 at diagnosis (range 65-96) and 51% were male. 79% (n = 2,247) were white, 14% (n = 403) African-American/Black, and 7% (n = 191) were another race. Overall, the median expenditure was $127,054 in the 12 months post-diagnosis; $121,400 for African-Americans, $127,810 for whites, and $119,209 for other races. After controlling for age, gender, comorbidities, a proxy measure of performance status, and MM related renal impairment and bone disease, African-American patients had $10,524 less in overall expenditures on average than white patients. This can partly be attributed to lower expenditures on MM drugs. On average African-American patients had $5,520 less in MM drug expenditures (p = 0.0062). African-Americans also had 9.3 less days of interaction with outpatient services compared to their white peers (p < 0.0001), but 4.6 more days in inpatient settings (p = 0.0208). There was no statistically significant difference between white patients and patients of races other than white or African-American in overall expenditure or MM drug expenditure but members of other races had 8.2 less days of interaction with outpatient services (p = 0.0004) and 5.7 less days in inpatient settings (p = 0.0350). The estimated median overall survival for African-American patients was 44 months (95% CI 40-51) compared to 47 (45-50) for white patients and 57 (44-66) for patients of other races (p = 0.097). Race was not associated with overall survival in multivariate analysis. Conclusion: Minority patients with MM received fewer services during the 12 months post-diagnosis. It is currently unclear if this is due to inferior care, overuse among white patients, or related to the clinical needs of the patients. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Champlin, Grace, Scott Hwang, Guolian Kang, Juan Ding, Jeremie H. Estepp, Kenneth I. Ataga, Curtis L. Owens, et al. "Progression of Central Nervous System Vasculopathy in Young Adults with Sickle Cell Anemia." Blood 134, Supplement_1 (November 13, 2019): 2290. http://dx.doi.org/10.1182/blood-2019-129193.
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Introduction Silent cerebral infarcts (SCI) and cerebral vessel stenosis are common and progressive in sickle cell anemia (SCA). Most data regarding brain lesions in SCA are cross-sectional or derive from pediatric cohorts with short follow-up not spanning the transition into adulthood. While hydroxyurea and transfusions may reduce the incidence of SCI and abnormal transcranial Doppler (TCD) in children with SCA, data on the effectiveness of these therapies in young adults are lacking. We tested the hypothesis that SCI and cerebral vessel stenosis progressed in young adults with SCA, relative to their childhood years. In addition, we explored the relationship between progression of brain vasculopathy and exposure to disease-modifying therapy. Methods We obtained brain magnetic resonance imaging (MRI) and MR angiography (MRA) in adults with SCA (HbSS or HbSβ0-thalassemia) on chronic transfusions or hydroxyurea. Participants were recruited from the IRB-approved longitudinal cohort study, Sickle Cell Clinical Research and Intervention Program (Hankins et al., PBC 2018). Participants were ages 18.0 to 32.0 at adult imaging and had at least one prior MRI/MRA between 0 and 17.9 years. Pediatric MRI/MRAs were performed for clinical indications (e.g., neurologic concern). All pediatric and adult MRI/MRAs had similar imaging protocols and were centrally reviewed by a neuroradiologist. SCIs were defined as focal T2-weighted or FLAIR hyperintensity. MRIs were considered abnormal if SCI or overt strokes were present. MRI progression was defined as new SCI or new overt strokes. Vessel stenoses were graded using a validated vasculopathy scale from 0 to 6 (Helton et al., Blood 2014). Abnormal MRA was defined as a score ≥1 and progression as any increase in the vasculopathy grading. We retrospectively ascertained childhood TCDs, treatments, overt strokes, and transient ischemic attacks (TIA, <24 hours neurologic symptoms with no imaging change). The proportion of abnormal brain MRI/MRA was calculated for the participants' pediatric (0-11.9), adolescent (12.0-17.9), and young adult (18.0-32.0) years and compared using multivariate generalized linear mixed model. Multivariate logistic regression investigated the association of exposure to hydroxyurea or chronic transfusion with MRI/MRA progression from child to adulthood. Results Forty-one young adults with SCA, all African American, median age 19.0 years, (range 18.0-31.5) were included (Table 1). All received disease-modifying therapy prior to adult MRI/MRA; median duration of hydroxyurea was 10.4 years (range, 0.3 to 20.35) and chronic transfusion was 9.2 years (range, 2.5 to 14.6). Indications for chronic transfusion were: abnormal TCD (N=6), overt stroke (N=4), recurrent vaso-occlusive events (VOE) (N=1), and chronic kidney disease (N=1). Indications for hydroxyurea were: VOE (N=27), overt stroke (N=1), and abnormal TCD (N=1). The total follow-up time from pediatric to adult brain MRI/MRA was 804 person-years, during which 2 patients had new strokes and 5 had TIAs. Progression of MRI and MRA occurred in 12 (29%) and 8 (20%) young adults, respectively, in relation to their pediatric exams (p=0.04 and p=0.01), both among hydroxyurea (Figure 1a) and transfusion (Figure 1b) groups. Both MRI and MRA progression occurred more frequently among those with prior stroke or conditional or abnormal TCD velocities, p=0.015. Controlling for age at adult imaging, exposure to hydroxyurea was associated with decreased probability of MRI progression (OR=0.05, 95%CI: 0.01~0.52, p=0.01), but not MRA (OR=0.22, 95%CI: 0.02~2.34, p=0.2). When further adjusting for transfusions, exposure to hydroxyurea was still associated with decreased probability of MRI progression (OR=0.05, 95%CI: 0.4~0.64, p=0.021) but not transfusions (OR 0.94, 95%CI: 0.16~5.39, p=0.95). Conclusion Close to a quarter of young adults with SCA treated with disease-modifying therapies for approximately a decade, experienced progression of brain lesions despite treatment with disease-modifying therapies. Among patients exposed to hydroxyurea, less progression of SCIs occurred. Overt stroke or TCD elevation in childhood increased the risk of brain lesion progression. In children with SCA, the presence of SCI and vessel stenosis in childhood should prompt consideration of alternative treatments given the evidence that brain lesions progress as they emerge into adulthood. Disclosures Kang: MBIO: Other: St. Jude Children's Research Hospital has an existing exclusive license and ongoing partnership with Mustang Bio for the further clinical development and commercialization of this XSCID gene therapy. Estepp:Forma Therapeutics: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Eli Lilly and Co: Research Funding; Pfizer: Research Funding; Esperion: Consultancy. Ataga:Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Modus Therapeutics: Honoraria; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. King:Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; Cell Works: Consultancy; Bioline: Consultancy; Celgene: Consultancy; Amphivena Therapeutics: Research Funding; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; RiverVest: Consultancy; WUGEN: Equity Ownership. Wang:Agios Pharmaceuticals: Consultancy; Novartis: Consultancy. Hankins:NHLBI: Honoraria; ASPHO: Honoraria; Novartis: Research Funding; LYNKS Foundation: Research Funding; Bluebird Bio: Consultancy; NHLBI: Research Funding; Global Blood Therapeutics: Research Funding; National Committee for Quality Assurance: Consultancy.
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Marlow, Emily C., Kristen Wehling, Karla Wysocki, Jacqueline Waldrop, and Arlen (Dewayne) Brumlow. "Abstract P6-05-49: Modeling a public-private grant initiative to address breast cancer care disparities at the community level." Cancer Research 83, no. 5_Supplement (March 1, 2023): P6–05–49—P6–05–49. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-05-49.
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Abstract Background: Breast cancer disparities between Black and White women have persisted in the US, with breast cancer death rates 40% higher in Black women compared to White women (American Cancer Society Cancer Facts & Figures for African American/Black People 2022-2024). Education and interventions at the community level can potentially reduce racial gaps, particularly in curbing late-stage diagnoses that disproportionately affect Black women with breast cancer. Together, the American Cancer Society (ACS) and Pfizer Global Medical Grants (Pfizer) developed a collaborative model to support health systems in engaging communities to reduce breast cancer disparities between Black and White women. This collaboration aimed to identify novel interventions and provide foundational support for these communities to advance their work in bridging the gap in breast cancer disparities. Methods: This collaborative grant program divided project responsibilities, in which Pfizer provided funding and ACS provided project oversight and technical support. An advisory committee provided input on the areas of most need, impact and project direction. Funding applicants were required to partner with local organizations to implement evidence-based initiatives for education and/or quality improvement within the respected community. The grant award selection committee comprised of experts in the field, including breast cancer survivors and individuals from racial/ethnic minority groups. In response to a Request for Proposals, over 100 applications were systematically reviewed based on the National Cancer Institute grant selection process. The committee selected 9 grantees with innovative proposals addressing breast cancer disparities for Black women along the cancer-care continuum. Bi-annual progress reports were used to measure progress, with a final report to mark projects’ impact and reach. The COVID-19 pandemic presented numerous obstacles during the project period and the ability to convene with partners virtually through web-based sessions helped to foster opportunities for collaboration and knowledge sharing among leaders in cancer disparities research. Results: The projects occurred from January 2020 to June 2022, with no-cost extensions given to accommodate COVID-19 pandemic delays. During this period grantees successfully completed project goals in one of three areas: screening, identifying areas of need and education. Approximately 10,000 patients and 200 healthcare professions were impacted among three projects focused on increasing mammography efforts in Black women during the project period. Three projects incorporated surveys and focus groups to identify novel areas for intervention/need and interviewed over 350 patients and over 60 health care professionals. The remaining three grantee projects that focused on education successfully implemented advertisement campaigns and lecture series to target patients and healthcare professionals. The projects selected under this model independently completed their goals within the project period while also laying a foundation to continue work in reducing disparities along the cancer care continuum with their enhanced community partner relations. Additionally, the project period also provided opportunities for external collaborations and discussion among all grantees through 8 ACS-coordinated online sessions and 3 summits. Conclusions: Projects selected by the public-private grant initiative model can enhance community relationships and provide infrastructure to continue work along the cancer care continuum. We believe this collaborative competitive grant program can be used for future efforts to address breast cancer and other health disparities at the community level. Similar collaborative funding projects related to prostate and pan-tumor disparities have been launched and are currently ongoing. Citation Format: Emily C. Marlow, Kristen Wehling, Karla Wysocki, Jacqueline Waldrop, Arlen (Dewayne) Brumlow. Modeling a public-private grant initiative to address breast cancer care disparities at the community level [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 P6-05-49.
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Shallal, Anita, Amit T. Vahia, Rachel Kenney, and Allison J. Weinmann. "11. Missed Vaccine Opportunities During the COVID-19 Pandemic." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S28—S29. http://dx.doi.org/10.1093/ofid/ofaa439.056.
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Abstract Background The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for all adults over the age of 65 to reduce S. pneumoniae pneumonia. Our institution follows a standing order for nurses to vaccinate adults who meet the Advisory Committee on Immunization Practices (ACIP) criteria. During the COVID-19 pandemic surge, the pneumococcal vaccine and influenza vaccine nurse-driven protocol was determined to be non-essential on 3/23, and 4/2 respectively. Our study aims to characterize missed vaccine opportunities among patients hospitalized with COVID-19 during this surge. Methods A retrospective cross-sectional study of PCR-positive COVID-19 patients admitted to an inner-city hospital and discharged alive between the dates of 3/23 and 4/21/2020. Patients under the age of 65 were excluded. Data collected included patient age, gender, race, length of stay, co-morbidities that would indicate a vaccine opportunity, prior vaccinations, and whether there was a vaccine opportunity for PPSV23 and influenza defined by ACIP indications. Vaccine history was evaluated using the electronic medical record (EMR) and Michigan Care Improvement Registry. If there was a vaccine opportunity, we documented whether a vaccine was given before hospital discharge. Total numbers of vaccines given for time periods in 2019 and 2020 were collected from EMR for comparison. Results 100 patients over the age of 65 were included. The average age was 72.8 years, and most patients (66%) were of African American race. The mean length of stay was five days. 52 patients were identified as having an opportunity to receive PPSV23, and 0 patients received the vaccine. 67.3% had more than one indication for PPSV23. 37 patients were eligible to receive influenza vaccine, and 0 received the vaccine. Results are summarized in table 1. Figures 1 and 2 display the number of pneumococcal and influenza vaccines given per EMR, respectively. Figure 1 Figure 2 Table 1 Conclusion Due to prioritization of potential staffing shortages and clustering nursing care, an opportunity to vaccinate patients with pneumococcal and influenza vaccines was missed. It is important for health care providers to be aware of this potential opportunity for vaccination of high-risk patients in order to promote primary prevention in future waves of pandemics. Disclosures All Authors: No reported disclosures
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Gray, Heewon, Jessica Berumen, Sharonda Lovett, David Himmelgreen, Dipayan Biswas, Joe Bohn, Caitlyn Peacock, Acadia Buro, and Whitney Van Arsdale. "Understanding Access to Healthy Foods and Grocery Shopping Patterns Among Community Residents in Underserved Neighborhoods in Tampa, Florida." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 194. http://dx.doi.org/10.1093/cdn/nzaa043_045.
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Abstract Objectives It is widely accepted that low-income and racial/ethnic minority neighborhoods are disproportionately affected by diet-related adverse health outcomes. Access to healthy foods has also been shown to be a determinant of more optimal dietary intake and health. This study aimed to conduct a survey to examine grocery shopping patterns and food access among community residents in underserved neighborhoods; the study was conducted in partnership with community organizations. Methods A survey was administered cross-sectionally. Twenty-seven questions adapted from previous research regarding grocery shopping patterns and food access were included. Community residents aged ≥18 years in East Tampa, a designated Florida Community Redevelopment Area (CRA), were recruited at community events/meetings, and an online version of the survey was distributed through the email listserv of community partners. A total of 126 residents participated; the majority was African American, female, and ≥35 years of age. Descriptive statistics were used for data analysis. GIS mapping was subsequently used to examine the residents’ accessibility to grocery stores within the neighborhoods. Results The majority (58%) of the participants reported that they usually buy most of their groceries at supermarkets, followed by large chain stores (41%), farmers markets (11%), and discount stores (10%). There were 4 major stores in the neighborhoods identified as preferred grocery stores. Most participants indicated that they use cash (52%) or EBT card (30%) for grocery shopping, and 33% regularly get food from food pantries. Most residents use their own cars (76%) for transportation and indicated that it takes ≤30 minutes (87%) to get their groceries. Ninety participants (71%) indicated that a new supermarket nearby would help them get food easier, followed by a new farmers market. In an open-ended question, some reported that mobile food trucks or delivery services would make it easier to get the foods. A specific location for a new supermarket was identified by each participant. Conclusions Community residents demanded a new supermarket or farmers market with better variety of fresh produce. The results of this study have been discussed with the community partners and the CRA advisory committee. Funding Sources University of South Florida, College of Public Health Internal Faculty Awards.
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Bhatnagar, Bhavana, Qiuhong Zhao, James L. Fisher, Jessica Kohlschmidt, Krzysztof Mrózek, Deedra Nicolet, Shelley Orwick, et al. "Poor Treatment Outcomes of Young (<60 Years) African American Patients (Pts) Diagnosed with Acute Myeloid Leukemia (AML) (Alliance)." Blood 136, Supplement 1 (November 5, 2020): 5–7. http://dx.doi.org/10.1182/blood-2020-140999.
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Background: AML is a clinically and molecularly heterogeneous disease associated with poor survival. Multiple disease-related factors including cytogenetic findings and gene mutations, as well as patient-related factors, such as demographics and African American (AA) heritage, have been identified that impact on pt outcomes. However, with recent improved survival it is unknown whether racial health disparities persist. Moreover, we are not aware of a large study that assessed possible race-associated molecular differences. Thus, the goals of our study were to 1) analyze the outcomes of adult AML pts in a nationwide population study, including possible impacts of sociodemographic, financial and racial disparities and 2) characterize molecular features of AA compared with those of Caucasian AML pts. Methods: For a nationwide population analysis, the Surveillance Epidemiology End Results (SEER) Program of the National Cancer Institute was used to identify 11,190 adults aged 18-60 years (y) diagnosed with AML (excluding acute promyelocytic leukemia) between 1986 and 2015. To characterize molecular features we performed targeted sequencing of 81 genes in 1,339 AML pts treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology (Alliance) protocols based on standard intensity cytarabine/anthracycline induction followed by consolidation between 1986 and 2016. No Alliance pt received an allogeneic stem cell transplant in 1st complete remission (CR). Results: The associations between demographic parameters and risk of death among SEER registry AML pts are shown in Table 1. While there was a slightly higher risk of death for men (HR 1.09) and a lower risk of death for pts with a higher median household income (>79.6k vs <54.4k, HR 0.85), the strongest factor affecting survival of AML pts was self-reported pt race, after accounting for other variables in the model. Specifically, AA AML pts had a higher risk of death compared with that of white AML pts (HR 1.28), with 3-year (y) overall survival (OS) rates of 32% and 41%, respectively (P<.001; Figure 1A). To evaluate if this race-associated survival disparity also persists in pts treated in the setting of clinical trials, we analyzed the survival of pts similarly treated on Alliance protocols. Although there was no difference in CR rates between AA and Caucasian Alliance AML pts, AA pts had inferior disease-free survival (DFS; median, 0.8 y vs 1.4 y, P=.02) and OS (median, 1.2 y vs 1.8 y, P=.02) compared with Caucasian pts, indicating that access to similar treatments might not alleviate racial survival disparities (Figure 1B). To assess whether any race-associated pretreatment features may help explain the different outcomes, we analyzed the clinical, cytogenetic and gene mutation features of the Alliance cohort. AA pts less often had normal cytogenetics (38% vs 51%, P=.01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%, P=.04) and higher frequencies of spliceosome gene mutations (24% vs 12%; P=.009) than Caucasian pts. Multivariable analyses for outcome in AA pts did not identify any molecular features associated with achievement of CR or DFS. However, AA pts harboring FLT3-ITD or IDH2 mutations had shorter OS compared with wild-type pts (FLT3-ITD, HR=1.95, P=.03; IDH2, HR=2.17, P=.008). Notably, other well-established mutational features known to associate with outcome (e.g., NPM1 or TP53 mutations) did not impact on survival. Lastly, we performed uni- and multivariable outcome analyses for OS in our Alliance pts. Remarkably, being NPM1-mutated and not being AA were the only positive prognostic factors associated with longer OS in the final risk model (NPM1 mut vs wt, HR=0.72, P<.001; Caucasian vs AA, HR=0.72, P=.03). Conclusion: Self-reported AA race is the most important pt-associated factor associated with poor survival in AML pts < 60 y of age based on SEER. Survival analyses in Alliance pts identify AA race as independent poor survival prognosticator in AML pts besides established molecular markers. . This disparity must be urgently addressed to ensure improved outcomes for AA AML pts, and larger studies to establish molecular risk profiles are needed. Support: U10CA180821, U10CA180882 U24CA196171, https://acknowledgments.alliancefound.org; Clinicaltrials.gov Identifiers: NCT00048958, NCT00899223, NCT00900224 Disclosures Bhatnagar: KaryoPharm Therapuetics: Research Funding; Cell Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; KITE: Membership on an entity's Board of Directors or advisory committees. Blachly:AbbVie, AstraZeneca, KITE Pharma: Consultancy. Mims:Novartis: Speakers Bureau; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Agios: Consultancy. Walker:Vigeo Therapeutics: Consultancy; Karyopharm: Current Employment, Current equity holder in publicly-traded company. Powell:Genentech: Research Funding; Jazz Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Pfizer: Research Funding; Rafael Pharmaceuticals: Consultancy, Other: Advisor, Research Funding; Novartis: Research Funding. Kolitz:Magellan: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Stone:Biolinerx: Consultancy; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Other; Aztra-Zeneca: Consultancy; Jazz: Consultancy; Argenix: Other; Janssen: Consultancy; Daiichi-Sankyo: Consultancy; Pfizer: Consultancy; Gemoab: Consultancy; Syndax: Consultancy, Research Funding; Takeda: Other: DSMB; Macrogenics: Consultancy; Trovagene: Consultancy; Syntrix: Other: DSMB; Abbvie: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Actinium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Arog: Consultancy, Research Funding; Syros: Consultancy; Stemline: Consultancy. Byrd:Trillium: Research Funding; Leukemia and Lymphoma Society: Other; Acerta Pharma: Research Funding; Syndax: Research Funding; Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Gilead, TG Therapeutics: Other; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, BeiGene: Research Funding; Pharmacyclics LLC, an AbbVie Company, Gilead, TG Therapeutics, Novartis, Janssen: Speakers Bureau; Kartos Therapeutics: Research Funding; Vincera: Research Funding; Novartis: Research Funding. Eisfeld:Karyopharm: Current Employment, Current equity holder in publicly-traded company; Vigeo Therapeutics: Consultancy.
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Jagosky, Megan H., Kyle L. Madden, Myra M. Robinson, Blake B. Goodbar, Manisha Bhutani, Preeya Patel, Rupali Bose, et al. "Outcomes in Transplant Eligible Multiple Myeloma African American Patients Appear Similar to Caucasian Patients." Blood 128, no. 22 (December 2, 2016): 2352. http://dx.doi.org/10.1182/blood.v128.22.2352.2352.
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Abstract Background: SEER Data from 1975-2008 show a stark disparity in the incidence of multiple myeloma (MM) in African Americans (AA) compared to Caucasians, with a 2-3 times higher incidence in AA. Differences in the incidence appear to be genetically driven, but remain poorly understood. Although AA patients appear to have a lower incidence of high risk cytogenetics [Greenberg G et al, Blood Cancer J 2015], their outcomes have not improved in the novel era therapy compared to Caucasian patients [Ailawahdi S et al, Blood Cancer J 2016]. Access to specialized disease-specific care (including access to a transplant center) due to socioeconomic status and lack of social support have been proposed as impediments to optimal care for AA MM patients. We prospectively examined newly diagnosed transplant eligible AA and Caucasian patients with MM at our institution to assess their transplant outcomes. Methods: The MM database was interrogated from March 2014-December 2015 for all autologous stem cell transplant (ASCT) eligible patients with MM. Clinical features, induction regimens, treatment responses and ASCT outcomes were compared between AA and Caucasian patients. Continuous variables were compared using nonparametric rank tests, while incidences and proportions were compared using Fisher's exact tests. Results: A total of 73 consecutive ASCT eligible MM patients were identified (32 AA, 41 Caucasian). There was no significant difference in sex distribution between the cohorts (p > 0.999). However, AA patients were significantly younger at the time of diagnosis with a median age of 56 years compared to a median age of 61 years in the Caucasian cohort (p = 0.008). Except for lower hemoglobin levels among AA patients, there were no statistically significant differences in any other clinical variable at diagnosis (lab features, serum LDH levels, ISS staging, IMWG risk stratification, cytogenetics, etc.) between the patient cohorts. Analysis of pre- and post- ASCT data showed similar response rates to induction therapy and outcomes with no statistically significant differences observed in pre-ASCT and post-ASCT depth of response (assessed by IMWG criteria) or 1-year progression free survival between the two cohorts. Conclusions: At our institution, AA patients with MM presented at a younger age than Caucasians. However, no significant differences in disease features were observed between the two groups at the time of initial presentation. A much higher proportion of AA MM patients (44%) underwent ASCT at our institution compared to other academic centers. Although longer follow-up is required, our data suggest that when AA patients with MM are provided similar access to care as Caucasian patients with MM, similar response rates to induction therapy and ASCT can be achieved. Disclosures Bhutani: Prothena: Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda Oncology: Research Funding, Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Symanowski:Caris Life Sciences: Consultancy; Ra Pharma: Consultancy; Eli Lilly & Co: Consultancy; Endocyte: Consultancy. Avalos:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Usmani:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Skyline: 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; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Novartis: Speakers Bureau.
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Zhang, Jing, Matthew Hadfield, Helen Swede, Biree Andemariam, and George Lykotrafitis. "Increased Adhesiveness of Red Blood Cells from Sickle Cell Trait Carriers after Exposure to Daunirubicin Breast Cancer Chemotherapeutic Agent." Blood 136, Supplement 1 (November 5, 2020): 5–6. http://dx.doi.org/10.1182/blood-2020-143324.
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Introduction: African-Americans (AA) with breast cancer continue to experience worse morbidity and mortality than white patients. In addition to barriers to care, an active area of investigation has been the etiology of the increased risk adverse events (AEs) related to chemotherapy. An emerging question is if sickle cell trait (i.e., heterozygotes for hemoglobin beta gene), present in an estimated 1 in 12 of the AA population, confers increased susceptibility to chemotherapy-related complications. We posit that conditions of high physiological stress might be manifest during systemic treatment with toxic agents resulting in alterations of red blood cells (RBCs). Using an experimental biomechanical model system, we hypothesized that RBCs from SCT carriers would be prone to increased adhesiveness after exposure to a common systemic anti-cancer agent used in breast cancer. Increased adhesiveness of RBCs can be a precipitating factor of blocked vasculature and subsequent sickling crises, potentially leading to AEs during treatment. Methods: Our study testedex vivoRBCs from two groups of healthy female participants: 20 African-American sickle cell trait carriers (AA-SCT); and 15 white subjects with wild-type hemoglobin (W-WT). Isolated RBCs were treated with scaled Daunorubicin (DNR) doses. The unbinding forces between αvβ3 ligands and intercellular adhesion molecule-4 (ICAM-4) receptors are reported using the frequency distribution, which states the percentage of events whose unbinding forces are within each width of the bin. We then compared the median values of the forces measured in experiments without and with treatment for each drug. The collective frequency (CF%) is related to the population of active ICAM-4 receptors and is defined as the percentage of all unbinding events divided by the total number of measurements, which is 32 × 32 =1024 for each cell multiplied by the number of tested cells for each blood sample. Results: For AA-SCT RBCs, pre-treatment baseline CF of active ICAM-4 receptors was 4.88 ± 0.87%, which was significantly increased after administration of DNR (13.13 ± 2.30%, p<0.0001). In contrast, treatment of W-WT RBCs held the CF of active ICAM-4 receptors at a comparable level as untreated RBCs (9.54 ± 1.48%; 7.47 ± 1.07%, p=0.50, respectively). Conclusion: Our findings could support hypotheses for adhesion-related RBC clumping among AAs with SCT during systemic treatment with anti-neoplastic agents, and, putatively, resultant AEs. Given past studies showing African-American women with breast cancer have higher rates of self-withdrawal from treatment, further exploration with additional systemic agents are warranted. Our novel study is limited by a small sample size as well lack of potential confounding factors in analyses. Future studies are planned with additional agent(s) and AAs without SCT. Should it be confirmed that SCT carrier status predicts RBC alterations during systemic treatment for breast cancer, and are linked to subsequent adverse events, it could lead to precision treatment planning. Disclosures Andemariam: Novartis:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Hemanext:Membership on an entity's Board of Directors or advisory committees;Global Blood Therapeutics:Consultancy, Membership on an entity's Board of Directors or advisory committees;Vertex:Honoraria;Imara:Research Funding;Emmaus:Membership on an entity's Board of Directors or advisory committees;bluebird bio:Consultancy, Membership on an entity's Board of Directors or advisory committees;NovoNordisk:Consultancy, Membership on an entity's Board of Directors or advisory committees;CRISPR/Vertex:Consultancy, Membership on an entity's Board of Directors or advisory committees;CHNCT:Consultancy;Accordant:Membership on an entity's Board of Directors or advisory committees;Guidepoint:Honoraria;Sanofi Genzyme:Consultancy, Membership on an entity's Board of Directors or advisory committees;Terumo BCT:Consultancy, Membership on an entity's Board of Directors or advisory committees;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Cyclerion:Consultancy, Membership on an entity's Board of Directors or advisory committees;Pfizer:Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Hwang, Amie E., Sikander Ailawadhi, Leon Bernal-Mizrachi, Todd M. Zimmerman, Christopher Haiman, David J. Van Den Berg, Karen Pawlish, et al. "Obesity In Young Adulthood Is Associated With Early Onset Multiple Myeloma In African Americans." Blood 122, no. 21 (November 15, 2013): 1872. http://dx.doi.org/10.1182/blood.v122.21.1872.1872.
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Abstract Introduction African-American ethnicity, male sex, older age and obesity are accepted risk factors for multiple myeloma (MM). Obesity early in life is a risk factor for many cancers, including MM; most studies have focused on populations of European origin. African-Americans have a higher prevalence of obesity than other populations, and may have a distinct genetic contribution to this condition. We established a multi-center collaborative study to investigate possible explanations for the excess risk of MM among African-Americans. The aim of the present case-case analysis was to determine whether body mass index (BMI) was associated with risk factors and clinical characteristics at presentation in African-American MM patients. Methods Patients diagnosed with active MM since January 1, 2009 were recruited from nine outpatient centers and three Surveillance, Epidemiology, End-Results Program (SEER) population-based cancer registries. Information on weight and height at 20 years of age and at 5 years prior to diagnosis was obtained from questionnaires. Clinical information collected included age at diagnosis, stage, percent plasmacytosis on bone marrow biopsy, β2 microglobulin level, Ig serotype, light vs. heavy chain disease, and presence of lytic bone lesions. BMI (ht/wt2) was categorized into 3 levels (normal <25, overweight 25-29, obese >30) according to World Health Organization standard. The Pearson chi-square test was used to test the association between BMI category, and risk factors and clinical characteristics. Mean ages at diagnosis across BMI categories were compared using linear regression and a t-test for trend calculated. Results To date, 1,044 African-American MM patients have been enrolled and of those, 1,014 provided a DNA sample. At present, 970 patients have completed a questionnaire, clinical records have been abstracted for 823 patients, and 509 patients have some information on gender, age at diagnosis, weight, height and clinical characteristics.The mean age at diagnosis was 59. Increasing BMI at age 20 was associated with younger age at diagnosis (p= 0.0004), whereas BMI at 5 years prior to diagnosis was not associated with age at diagnosis (p=0.9477). Among men, mean age at diagnosis decreased with increasing BMI at age 20 (p= 0.0125) (Table 1a) and at 5 years prior to diagnosis (p=0.0252) (Table 1b). Among women, the trend was signficant at age 20 (p=0.0018) (Table 1a) but not at 5 years prior to diagnosis (p= 0.7094) (Table 1b). Increasing BMI was not significantly associated with any other clinical characteristics. Conclusion/Discussion In a large collection of African-American MM patients, we observed a strong association between increasing BMI at age 20 and younger age at diagnosis. A similar trend was observed in men only at 5 years prior to diagnosis, consistent with previous reports. Obesity is one of the few known potentially modifiable risk factors for MM. Younger age at diagnosis reflects an earlier accumulation of either or both genetic and environmental risk factors. Obesity at an early age may influence MM risk through shared biological pathways such as interleukin-6 and insulin-like growth factor, by contributing to chronic B-cell activation, thereby increasing susceptibilty for MM later in life. The significance of the gender difference for the association closer to diagnosis is unclear and requires additional study. Disclosures: Terebelo: Amgen: Honoraria; Millennium: Honoraria. Mehta:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Zonder:Skyline: Consultancy. Orlowski:Bristol-Myers Squibb: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millennium: The Takeda Oncology Company: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Resverlogix: Research Funding; Array Biopharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Membership on an entity’s Board of Directors or advisory committees. Lonial:Celgene Corporation: Consultancy; Millennium: Consultancy; Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.
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Jagosky, Megan H., Kyle L. Madden, Blake B. Goodbar, Virginia Thurston, Manisha Bhutani, Preeya Patel, Myra M. Robinson, et al. "Fluorescence in Situ Hybridization (FISH) abnormalities and Baseline Clinical Features at Diagnosis in African American Multiple Myeloma Patients." Blood 128, no. 22 (December 2, 2016): 2351. http://dx.doi.org/10.1182/blood.v128.22.2351.2351.
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Abstract BACKGROUND: Multiple myeloma (MM) is the most common hematologic malignancy in the African American (AA) population with an incidence more than 2-3 times higher than Caucasians [Landgren O et al Blood 2006]. In the pre-novel therapy era, SEER data [1975-2008] indicated better survival outcomes for AA patients with MM. However, with the recent advent of novel drugs for treatment of MM, the survival gap for Caucasian patients with MM has closed [Ailawadhi S et al Br J Haematol 2012]. A recent pooled analysis of diagnostic cytogenetics in 292 AA MM patients [Greenberg et al Blood Cancer J 2015] reported on differences in commonly observed baseline cytogenetic abnormalities (CA) between AA and Caucasian MM patients. The large and diverse population of patients with MM at our institution prompted us to examine diagnostic cytogenetics in our MM patients along with other clinical features. PATIENTS & METHODS: The MM database was interrogated for all patients presenting with MM between January 2012 and February 2016. Baseline clinical and pathology variables were compared between the AA and Caucasian cohorts. Continuous variables were compared using nonparametric rank tests, while incidences and proportions (e.g. CAs including t(11;14), t(4;14), t(14;16), t(14:20), amplification 1q21, monosomy13/del13q and del17p) were compared using Fisher's exact tests. RESULTS: A total of 398 patients were identified for the analysis (African Americans n = 168, Caucasian n = 230). The median age of AA MM patients was significantly younger than Caucasian MM patients (median age 63 years vs. 68 years, p<0.0001), with a similar sex distribution. There was no significant difference in the degree of anemia, renal insufficiency, serum LDH levels, bone marrow flow cytometry, bone marrow cellularity or plasmacytosis in the two cohorts. Although there was a trend toward more ISS I amongst Caucasian MM patients, there was no statistical difference in ISS stages (p = 0.126) and no significant difference in R-ISS stage between the cohorts (p = 0.361). There was 72.7% agreement between the ISS and R-ISS staging (88 of 121 evaluable subjects had the same stage by ISS and R-ISS staging criteria), while 27.3% of the patients were upstaged from Stage I or II by ISS criteria to Stage III by R-ISS criteria. Of those upstaged, 19 patients were in the Caucasian cohort and 14 were in the AA cohort. The magnitude of this upstaging was significant when evaluated with a Generalized McNemar's test (p < 0.001). Additionally, there was a similar incidence of common FISH abnormalities in the AA cohort compared to the Caucasian cohort [Table 1]. CONCLUSIONS: This is the largest single institution report of FISH data in AA MM patients. Unlike previous reports, we show similar clinical, pathological, and cytogenetic features between AA and Caucasian patients with MM at presentation. It is possible that molecular abnormalities not detectable by FISH in our patient cohort could account for differences in our data and the published literature. Table 1 FISH Abnormalities Table 1. FISH Abnormalities Disclosures Bhutani: Prothena: Research Funding; Takeda Oncology: Research Funding, Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Onyx, an Amgen subsidiary: Speakers Bureau. Symanowski:Eli Lilly & Co: Consultancy; Ra Pharma: Consultancy; Caris Life Sciences: Consultancy; Endocyte: Consultancy. Avalos:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Usmani:Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Pharmacyclics: Research Funding; BioPharma: 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, Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau; Novartis: Speakers Bureau.
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Pipe, Steven W., Francesca Ferrante, Muriel Reis, Sara Wiegmann, Claudia Lange, Manuela Braun, and Lisa A. Michaels. "First-in-Human Gene Therapy Study of AAVhu37 Capsid Vector Technology in Severe Hemophilia A - BAY 2599023 has Broad Patient Eligibility and Stable and Sustained Long-Term Expression of FVIII." Blood 136, Supplement 1 (November 5, 2020): 44–45. http://dx.doi.org/10.1182/blood-2020-139803.
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Background Gene therapy for hemophilia A has the potential to reduce the treatment burden for patients and their care providers by eliminating the need for regular factor VIII (FVIII) prophylaxis through long-term expression of endogenous FVIII at levels sufficient to provide bleed protection. Host immunity to the capsid serotype limits patients' eligibility and may impact the balance between vector dose and clinical outcome. BAY 2599023 (AAVhu37FVIII) is the first clinical-stage adeno-associated virus (AAV) gene therapy vector based on the AAVhu37 serotype. BAY 2599023 is a non-replicating AAV vector and contains a single-stranded DNA genome encoding a B-domain-deleted FVIII, under the control of a liver-specific promoter/enhancer combination optimized for transgenic expression. The AAVhu37 capsid is a member of the hepatotropic clade E family, and was selected based on preclinical studies demonstrating efficient liver-directed FVIII gene transfer, favorable biodistribution and durable FVIII expression. However, pre-existing humoral immunity against AAV capsids may limit patient eligibility. Here, we evaluate the seroprevalence and titer levels of pre-existing neutralizing antibodies (Nabs) against AAVhu37, and additional AAV capsids, using cell-based transduction inhibition assays. We also report current, preliminary, long-term safety and FVIII activity following a single intravenous infusion of BAY 2599023, in a phase 1/2 open-label, first-in-human, dose-finding study (NCT03588299). Methods Seroprevalence and titer distribution of Nabs against AAVhu37, AAV5 and AAV8 have been assessed in serum samples derived from 100 US patients with hemophilia A (African American and Caucasian male donors, 19-61 years). For AAVhu37, the clinical trial Nab assay was utilized to determine Nab titer levels according to cellular transduction inhibition. Additionally, we developed and fully validated Nab assays for AAV5 and AAV8. The ongoing BAY 2599023 phase 1/2 dose-finding study included male patients aged ≥18 years with severe hemophilia A, each receiving a single intravenous infusion of BAY 2599023. Patients were enrolled sequentially into three dose cohorts (0.5 × 1013 GC/kg, 1.0 × 1013 GC/kg and 2.0 × 1013 GC/kg), each comprising two patients. Patients had no history of FVIII inhibitors, no detectable neutralizing immunity against the AAVhu37 capsid above a Nab titer of 1:5, and ≥150 exposure days to FVIII products. Primary endpoints were adverse events (AEs), serious AEs (SAEs) and AEs/SAEs of special interest (S/AESIs). The secondary endpoint was change in FVIII activity from baseline. Informed patient consent and ethics committee approval were obtained. Results In the seroprevalence study, the lowest pre-existing Nab prevalence was found for AAVhu37, with a low maximum observed titer of 1:26. Based on our results, 86% of patients would be eligible for AAVhu37-based treatment (Table 1). To date, patients in the first (0.5 × 1013 GC/kg) and second cohort (1.0 × 1013 GC/kg) have completed ≥52 weeks of observation; patients in cohort 3 (2.0 × 1013 GC/kg) have at least 33 weeks of observation. Regardless of the level achieved and the assay used, 5 out of 6 of patients show sustained FVIII levels (all ≥5%) over time and up to 16 months. Patients in cohorts 2 and 3 have all been off prophylaxis since ~6 weeks after gene transfer. No spontaneous bleeds were reported after achieving protective FVIII levels (>15 IU/dL) and discontinuation of prophylaxis in the third cohort. No SAEs have been reported to date. Mild-to-moderate elevation in alanine aminotransferase/aspartate aminotransferase were recorded for one patient in the second cohort and both patients in the third cohort. All were treated with corticosteroids (one resolved, two in resolution). The latest follow-up data for up to 22 months will be presented. Conclusions BAY 2599023 has a broad patient eligibility due to low seroprevalence and low titers of pre-existing Nabs against AAVhu37 compared with other AAVs. BAY 2599023 has a good safety profile, with the potential to achieve endogenous expression of FVIII at therapeutic levels over an extended period. Successful proof-of-concept has been achieved, with measurable and sustained expression of endogenous FVIII. Disclosures Pipe: Apcintex, Bayer, BioMarin, Catalyst Biosciences, CSL Behring, HEMA Biologics, Freeline, Novo Nordisk, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, Inc., Sangamo Therapeutics, Sanofi, Takeda, Spark Therapeutics, uniQure: Consultancy; Siemens: Research Funding; Medical and Scientific Advisory Council to the National Hemophilia Foundation; Medical Advisory Board to World Federation of Hemophilia: Membership on an entity's Board of Directors or advisory committees. Ferrante:Bayer: Current Employment. Reis:Bayer: Current Employment. Wiegmann:Bayer: Current Employment. Lange:Bayer: Current Employment, Current equity holder in private company. Braun:Bayer: Current Employment, Current equity holder in private company. Michaels:Bayer: Current Employment.
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Marshall, Mazepa A., Michael Evans, Elizabeth Davis, Andrew Johnson, Ana G. Antun, Andrew M. Farland, Ryan R. Woods, et al. "Differential Effect of Rituximab on Relapse-Free Survival in De Novo and Relapsed Immune Thrombotic Thrombocytopenic Purpura in African-American and Caucasian Populations." Blood 134, Supplement_1 (November 13, 2019): 90. http://dx.doi.org/10.1182/blood-2019-129383.
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Introduction The United States Thrombotic Microangiopathy (USTMA) Consortium consists of high-volume US referral centers that are committed to collaborative research in TMAs. The USTMA Immune Thrombotic Thrombocytopenic Purpura (iTTP) registry has compiled retrospective data on demographics, treatments and outcomes in patients with iTTP to create the world's largest database of patients with this rare disease. While there is consensus on the use of therapeutic plasma exchange (TPE) for treatment of iTTP, there are no large randomized trials on which to base use of rituximab. The drug is frequently used for refractory or relapsed iTTP, but is currently being used more frequently for de novo (first episode) iTTP. We queried the USTMA iTTP registry to determine whether relapse free survival (RFS) is superior when rituximab is added to TPE and corticosteroids for treatment of iTTP. We hypothesized that the addition of rituximab would improve RFS at 5 years in both de novo and relapsing iTTP. Methods Following IRB approval at each institution, investigators independently reviewed individual patient records to confirm diagnostic criteria and entered demographic, treatment and outcomes data into the REDCap database housed at the University of North Carolina. The diagnosis of iTTP was defined as ADAMTS13 < 10% or ADAMTS13 < 20% with an inhibitor or antibody detected at any point or a clinical diagnosis of iTTP based on presenting characteristics, response to treatment and/or relapsing phenotype before ADAMTS13 testing became available (N=173). Relapse was defined as a recurrence of iTTP after at least 30 days of remission (recurrence within 30 days was considered an exacerbation, or continuation of the prior episode). To explore the effect of rituximab added to TPE and corticosteroids, we first assessed the treatment effect in de novo iTTP patients and then separately in relapse. We constructed Kaplan-Meier curves to compare RFS for patients treated with rituximab plus corticosteroids versus corticosteroids alone in both groups, and compared RFS at specific time points using the Klein method. To better understand whether other patient variables had an effect on RFS in both de novo episodes and relapses, ordinary (time-to-event) and mixed-effects (recurrent time-to-event) Cox proportional hazards models were used to examine the relationships of treatment, race/ethnicity, sex, age, treatment year, and presenting signs/symptoms with the outcome. Analyses were conducted using R version 3.5.2 (R Foundation for Statistical Computing, Vienna, Austria). Results As of July, 2019, the USTMA database contains 775 unique study patients with a confirmed diagnosis of iTTP with 1397 unique iTTP episodes. The treatment of patients' de novo iTTP episode was available for analysis in 375 patients, 188 of whom were treated with corticosteroids alone, 131 with corticosteroids plus rituximab, and 56 with other therapies. RFS was significantly higher in patients treated with corticosteroids and rituximab compared to those treated with corticosteroids alone at 1 year (0.93 vs. 0.78, p=0.0002) and 3 years (0.82 vs. 0.66, p=0.004) but not 5 years (0.60 vs. 0.56, p=0.39). In addition, the risk of relapse decreased with later treatment year for de novo iTTP (hazard ratio (HR) 0.95, 95% CI 0.92-0.99, p=0.03), consistent with rituximab use increasing over time, and was increased in African Americans compared with Caucasians (HR 1.83, 1.10-3.06, p=0.02). We then explored the treatment effect in all iTTP relapses (743 relapses in 426 patients). Here, a significant (p=0.0007) interaction between treatment and race was found. Among African Americans, we found no difference in RFS when rituximab was added (HR 1.15, 0.81-1.62, p=0.43). However, among Caucasians, RFS was significantly improved when rituximab was added (HR 0.15, 0.06-0.35, p<0.0001). Conclusions For de novo iTTP, adding rituximab to corticosteroids for immunosuppression likely delays but does not prevent relapse. Unlike in de novo disease, in patients with relapsed iTTP, we found a novel and significant interaction between race and treatment: while Caucasians had significantly improved RFS with the addition of rituximab, there was no effect on RFS in African Americans. Further investigation is warranted to determine the mechanisms of this difference in the response to rituximab in relapsed iTTP to improve outcomes in African Americans. Figure Disclosures Marshall: Sanofi: Membership on an entity's Board of Directors or advisory committees. Farland:Sanofi: Membership on an entity's Board of Directors or advisory committees. Metjian:Sanofi: Membership on an entity's Board of Directors or advisory committees. Raval:Bayer, Inc: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Liles:Imara: Other: PI on Clinical trial- Sickle cell ; Shire: Other: PI on clinical trial Sickle cell ; Novartis: Other: PI on clinical trial Sickle cell . Baumann Kreuziger:CSL Behring: Consultancy; Vaccine Injury Compensation Program: Consultancy. McCrae:Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees. Chaturvedi:Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy. Zheng:Clotsolution: Other: Co-Founder; Shire/Takeda: Research Funding; Ablynx/Sanofi: Consultancy, Speakers Bureau; Alexion: Speakers Bureau. Cataland:Ablynx/Sanofi: Consultancy, Research Funding; Alexion: Consultancy, Research Funding. Off Label Disclosure: rituximab for immunosuppression in TTP.
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Portacolone, Elena, Nynikka Palmer, Peter Lichtenberg, Catherine Waters, Carl Hill, Sahru Keiser, and Julene K. Johnson. "Earning the Trust of African American Communities to Increase Representation in Dementia Research." Innovation in Aging 4, Supplement_1 (December 1, 2020): 878. http://dx.doi.org/10.1093/geroni/igaa057.3244.
Full textAbstract:
Abstract Black/African American populations are underrepresented as participants in dementia research. A major barrier to participation of African American older adults in dementia research is a tendency to distrust research institutions owing to a legacy of racism. Building on the Ford framework, the objective of our study was to examine factors that influence participation in dementia research among African American older adults and caregivers, with an emphasis on understanding factors related to trust. Data were collected from 10 focus groups with African American older adults (n=91), 5 focus groups with caregivers (n=44), and interviews with administrators of community-based organizations (n=11), and meetings with our Community Advisory Board. Inductive/deductive content analysis was used to identify themes. The results identified an overall tension between distrust of researchers and a compelling desire to engage in dementia research. This overarching theme was supported by six themes that provided insights about the multiple layers of distrust, as well as expectations about the appropriate conduct of researchers and academic institutions. Strong commitment to the community was identified as a priority. The findings suggest that a paradigm shift is needed to increase the representation of African Americans in dementia research. In this new paradigm, earning the trust of African American communities becomes a systemic endeavor, with academic, state and national institutions deeply committed to earning the trust of African American communities and guiding researchers in this endeavor. The findings also generated actionable recommendations to help improve representation of African American older adults in dementia research.
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Liu, Angela, Marshall Mazepa, Elizabeth Davis, Andrew Johnson, Ana G. Antun, Andrew M. Farland, Ryan R. Woods, et al. "African American Race Is Associated with Decreased Relapse-Free Survival in Immune Thrombotic Thrombocytopenic Purpura." Blood 134, Supplement_1 (November 13, 2019): 1066. http://dx.doi.org/10.1182/blood-2019-131064.
Full textAbstract:
Background: Immune thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal hematologic disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic organ impairment. The incidence of iTTP is higher among African-Americans (AA), however, differences in presentation and outcomes have not been fully investigated. In a multi-center cohort of patients with iTTP from the United States Thrombotic Microangiopathy (USTMA) Consortium, we tested the hypothesis that AA race is an independent predictor of poor outcomes including iTTP related mortality and relapse. Methods: We queried data from the USTMA iTTP registry, which currently includes data from 785 individual patients from 15 institutions across the United States. Data from at least one iTTP episode are available for 734 patients. The cohort is 35.1% (N = 272) White, 58.7% (N = 455) African American, 0.4% (N=3) Asian, 1.8% (N=14) Hispanic, and 4.0 % (N=31) other/unknown race. We restricted our analyses to AA and White participants because of small numbers in the other groups. We compared presenting features and treatments using the chi-squared test and t-test for categorical and continuous variables, respectively. A relapse was defined as a recurrent iTTP episode occurring at least 30 days after last therapeutic plasma exchange. To evaluate relapse-free survival, we included only patients enrolled in the registry at their first TTP episode (144 White and 246 AA) since patients presenting with a relapse as their index episode are already confirmed to have relapsing iTTP. Kaplan Meier analysis was used to compare relapse-free survival in White and AA patients, and a Cox regression model was developed to evaluate the independent effect of race on relapse, adjusting for potential confounders including age, sex, and the use of rituximab. Results: Demographics and presenting features of 390 individuals (144 White and 246 AA) presenting with a first episode of iTTP are shown in Table 1. Presenting symptoms including fever, confusion, seizure, memory deficits, stupor, headache, stroke, chest pain, abdominal pain, fatigue, and dark urine were similar between Whites and AA except for petechiae, which were more frequently documented in Whites (28.8% vs 17.7%, p=0.011). Presenting laboratory studies were also comparable though AA had a higher rate of elevated serum troponin (50.6% vs 32.5%, p=0.003), lower hemoglobin level (8.27 ± 0.13 vs 8.81 ± 0.19, p=0.0176) and platelet count (20.3 ± 1.2 vs 26.2 ± 3.2, p=0.0432). In addition to therapeutic plasma exchange and corticosteroids, rituximab was administered to 23.7% of White patients and 22.7% of AA during their first iTTP episode (P=0.815). Median time to platelet count recovery (days of daily plasma exchange until normal platelet count for two consecutive days) was shorter in AA compared with White patients [5 (IQR 4, 10) vs. 8 (IQR 5, 14), log rank P = 0.004]. AA race remained a significant predictor of the shorter time to platelet count recovery [HR 1.44 (95% CI 1.12, 1.85), P=0.004] after adjusting for rituximab therapy [HR 0.60 (95% CI 0.0.46, 0.80), P<0.001], female sex [HR 0.95 (95% CI 0.73, 1.22), P=0.669], age [HR 0.99 (95% CI 0.99, 1.01), P=0.682], platelet count [HR 1.00 (95% CI 0.99, 1.04), P=0.820] and LDH at presentation [HR 1.00 (95% CI 1.00, 1.00), P=0.525]. Death during the first episode occurred in 8.9% of White patients and 5.5% of AA patients (P=0.206). Relapse-free survival after the first episode of iTTP was lower in AA than White patients (Figure 1). AA race was associated with the reduced relapse free survival [HR 1.79 (95% CI 1.08, 2.98), P=0.024] in a Cox regression model adjusted for age [HR 1.00 (95% CI 0.98, 1.01), P=0.683], sex [HR 0.96 (95% CI 0.60, 1.54), P=0.867], and rituximab therapy [HR 0.93 (95% CI 0.55, 1.59), P=0.806]. Conclusion: African Americans with iTTP have a higher relapse rate and shorter relapse free survival after the first episode of the disease compared with Caucasian patients, which is independent of age, sex and rituximab therapy. Contrary to our hypothesis, acute outcomes of iTTP (time to platelet count recovery and mortality) were not worse in AA patients. The factors contributing to the higher relapse rate in AA with iTTP need to be further investigated. Our findings suggest that AA patients may also benefit from closer follow up. Disclosures Farland: Sanofi: Membership on an entity's Board of Directors or advisory committees. Metjian:Sanofi: Membership on an entity's Board of Directors or advisory committees. Raval:Bayer, Inc: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Liles:Shire: Other: PI on clinical trial Sickle cell ; Imara: Other: PI on Clinical trial- Sickle cell ; Novartis: Other: PI on clinical trial Sickle cell . Baumann Kreuziger:CSL Behring: Consultancy; Vaccine Injury Compensation Program: Consultancy. McCrae:Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Sanofi Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Zheng:Alexion: Speakers Bureau; Ablynx/Sanofi: Consultancy, Speakers Bureau; Clotsolution: Other: Co-Founder; Shire/Takeda: Research Funding. Cataland:Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding. Chaturvedi:Shire/Takeda: Research Funding; Sanofi: Consultancy; Alexion: Consultancy.
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Portacolone, Elena, Nynikka R. Palmer, Peter Lichtenberg, Catherine M. Waters, Carl V. Hill, Sahru Keiser, Leah Vest, et al. "Earning the Trust of African American Communities to Increase Representation in Dementia Research." Ethnicity & Disease 30, Suppl (November 19, 2020): 719–34. http://dx.doi.org/10.18865/ed.30.s2.719.
Full textAbstract:
Black/African American populations are underrepresented as participants in dementia research. A major barrier to participation of African American older adults in dementia research is a tendency to distrust research institutions owing to both historical and contemporary racism. Building on the Ford framework, the objective of our study was to examine factors that influence participation in dementia research among African American older adults and caregivers, with an emphasis on understanding factors related to trust. Data were collected during January 2019 and March 2020 from 10 focus groups with African American older adults (n=91), 5 focus groups with caregivers (n=44), and interviews with administrators of community-based organizations (n=11), and meetings with our Community Advisory Board. Inductive/deductive content analysis was used to identify themes. The results identified an overall tension between distrust of researchers and a compelling desire to engage in dementia research. This overarching theme was supported by six themes that provided insights about the multiple layers of distrust, as well as expectations about the appropriate conduct of researchers and academic institutions. Strong commitment to the community was identified as a priority. The findings suggest that a paradigm shift is needed to increase the representation of African Americans in dementia research. In this new paradigm, earning the trust of African American communities becomes a systemic endeavor, with academic, state, and national institutions deeply committed to earning the trust of African American communities and guiding researchers in this endeavor. The findings also generated actionable recommendations to help improve representation of African American older adults in dementia research.Ethn Dis. 2020;30(Suppl 2):719-734; doi:10.18865/ed.30.S2.719
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Kansagra, Ankit, Angela Dispenzieri, Raphael Fraser, Noel Estrada-Merly, Shaji Kumar, Muzaffar H. Qazilbash, Nina Shah, and Anita D'Souza. "Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplant (ASCT) for Patients with POEMS Syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Protein, Skin Changes): A CIBMTR Analysis." Blood 138, Supplement 1 (November 5, 2021): 120. http://dx.doi.org/10.1182/blood-2021-151325.
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Abstract Introduction POEMS syndrome is a rare disease associated with a plasma cell dyscrasia with limited information regarding the role of ASCT. Small single institution series have demonstrated deep and durable responses after ASCT along with neurological improvement. Despite these benefits, ASCT is thought to have higher treatment related morbidity and mortality, limiting its use. We describe the outcomes from an international multicenter database of patients with POEMS syndrome undergoing ASCT. Methods We performed a retrospective analysis using the Center for International Blood and Marrow Transplant Research (CIBMTR) database to evaluate the outcomes of patients undergoing ASCT for POEMS syndrome. Standard descriptive methods were used to report patient characteristics. Univariate and multivariate analysis were performed to identify predicators for non-relapse mortality (NRM), relapse, progression-free and overall survival (PFS, OS). NRM was compared between POEMS and multiple myeloma (MM) patients who underwent ASCT during the same time period. Results Between 2008-2018, 331 pts with POEMS syndrome who underwent ASCT were identified. The median age was 51 years, with 66% males. Racial distribution was 65% Caucasians, 19% African American, 5% other, and 10% missing. Pre-transplant characteristics included 70% patients had Karnofsky score <90, and 50% had HCT-CI ≥ 3, reflecting underlying disease severity and symptoms. The most common comorbidity was pulmonary (52%). Only 14% of patients were in very good partial response or better at the time of ASCT and 72 (22%) patients underwent ASCT without prior treatment. The median time from diagnosis to ASCT was 7 months and 74% underwent ASCT within 12 months of diagnosis. The most common mobilization strategy was GCSF +/- plerixafor in 50% of pts and 87% of pts received conditioning with 200mg/m2 of Melphalan. The median follow up was 48 (range 3-137) months. At day 100, NRM was 0.9 % (95% CI: 0.2-2.2%). At 4 years, NRM was 4.9% (95% CI: 2.6-7.9%), relapse 15.4% (95% CI 11.3-20.1%), PFS 79.7% (95% CI 74.5-84.3%) and OS 92% (95% CI 89.2-95.6%). Subsequent neoplasms were seen in 16 (5%) with 4 myeloid malignancy and 12 solid tumors. On multivariate analysis, age ≥ 60 years was associated with greater hazards of mortality, HR 2.6 (95% CI 1.2-5.6), p 0.01. The figure shows the comparable NRM between POEMS and MM (p 0.31). Conclusions: We report outcomes of the largest ASCT series of POEMS patients. Despite a high HCT-CI and low functional status among patients with POEMS syndrome, no difference in NRM was seen when compared to MM. Post-transplant outcomes were excellent and support single center data on the role of ASCT in this rare disease. Figure 1 Figure 1. Disclosures Kansagra: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Alynylam: Membership on an entity's Board of Directors or advisory committees; Cota Health: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Dispenzieri: Alnylam: Research Funding; Pfizer: Research Funding; Sorrento Therapeutics: Consultancy; Takeda: Research Funding; Oncopeptides: Consultancy; Janssen: Consultancy, Research Funding. Kumar: Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; BMS: Consultancy, Research Funding; Oncopeptides: Consultancy; Beigene: Consultancy; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Honoraria; Novartis: Research Funding; Bluebird Bio: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Carsgen: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Qazilbash: Bristol-Myers Squibb: Other: Advisory Board; NexImmune: Research Funding; Janssen: Research Funding; Biolline: Research Funding; Oncopeptides: Other: Advisory Board; Angiocrine: Research Funding; Amgen: Research Funding. Shah: GSK: Consultancy; Karyopharm: Consultancy; Oncopeptides: Consultancy; Indapta Therapeutics: Consultancy; Janssen: Research Funding; Nektar: Research Funding; Bluebird Bio: Research Funding; Teneobio: Research Funding; CareDx: Consultancy; BMS/Celgene: Research Funding; Sanofi: Consultancy; Sutro Biopharma: Research Funding; CSL Behring: Consultancy; Poseida: Research Funding; Precision Biosciences: Research Funding; Amgen: Consultancy; Kite: Consultancy. D'Souza: Sanofi, Takeda, Teneobio, CAELUM, Prothena: Research Funding; Imbrium, Pfizer, BMS: Membership on an entity's Board of Directors or advisory committees; Janssen, Prothena: Consultancy.
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Nakar, Charles T., Marilyn J. Manco-Johnson, Alice Lail, Sharyne M. Donfield, Jennifer Maahs, Young Chong, Taylor A. Blades, and Amy D. Shapiro. "Prompt Immune Tolerance Induction at Inhibitor Diagnosis Regardless of Titer May Increase Overall Success in Hemophilia A With Inhibitors: Experience of Two US Centers." Blood 122, no. 21 (November 15, 2013): 575. http://dx.doi.org/10.1182/blood.v122.21.575.575.
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Abstract Introduction Immune tolerance induction (ITI) for patients (pts) with hemophilia A with inhibitors is the only modality known to effectively eradicate inhibitors with an overall reported success of ∼60-80%. One debate concerns the optimal time to start ITI; recent guidelines recommend delaying ITI until inhibitor titer is <10 Bethesda units (BU). Aim We report results of an analytic project to determine the success of ITI relative to time from inhibitor detection to ITI initiation. Methods Data was collected retrospectively at 2 US hemophilia centers on pts with severe/moderate (≤5%) factor VIII (FVIII) deficiency undergoing ITI including time interval from inhibitor detection to ITI start, inhibitor titer and outcome. High-dose ITI was practiced by both centers (i.e. ≥100 IU/kg/day). Success, partial success and failure were defined practically with success as a negative inhibitor titer and ability to use FVIII concentrate routinely for treatment and prevention of bleeding; partial success was an inhibitor titer <5 BU with ability to use FVIII concentrate to treat bleeding episodes; failure as ongoing ITI >3 years without achieving success/partial success or discontinuation of ITI. IRB approvals were obtained at both centers for this data analysis. Pts were first divided into low responding inhibitor (LRI) and high responding inhibitor (HRI) based on peak inhibitor titer; the HRI subgroup was further subdivided based on time to start ITI, including within 1 month, 1-6 months and greater than 6 months. The HRI subgroup starting ITI within 1 month was analyzed based on pre-ITI inhibitor titer. Results Fifty eight male pts with adequate ITI history documentation were included; 55 (95%) were severe (<1%), 3 moderately deficient (1-3%). Forty-seven pts (48%) were Caucasian, 6 Hispanic, 2 African American, 2 Asian and 1 Native American. Outcome is summarized in Table 1. Overall, 49 of 58 pts (84%) underwent successful ITI. Low responding Inhibitors: Among 19 (33%) pts with LRI, ITI success was 100%. Most pts with LRI 15/19 (79%) started ITI within 1 month from inhibitor detection. High responding inhibitors: Among 39 (67%) pts with HRI, 30/39 (77%) achieved tolerance, 1 achieved partial success and continued ITI, 1 was ongoing, 7 pts failed. The 39 pts with HRI were further subdivided based on time to ITI start. ITI start within 1 month of detection: Twenty three pts started ITI within 1 month from detection; 21 achieved success (91%), 1 partially succeeded and 1 failed. Eight of 10 pts (80%) with a pre-ITI titer <10 BU achieved success, 1 partially succeeded and 1 failed. All 13 pts (100%) starting ITI with pre-ITI inhibitor titer ≥ 10 BU achieved success. ITI start > 6 months: Eleven pts had an interval > 6 months until ITI start; 7 (64%) achieved success and 4 (36%) failed. Conclusions These results suggest that the time interval from inhibitor detection to start of ITI may play a critical role in outcome. A titer ≥10 BU did not influence outcome in pts where ITI was utilized within 1 month, supporting this approach in contrast to the commonly accepted practice of delaying ITI start until a titer <10 BU is achieved. Pts may benefit from prompt ITI regardless of current inhibitor titer and are not subjected to wait periods where bleeding is more likely to occur. Prompt ITI should be considered a viable therapeutic option in newly identified inhibitor pts regardless of current inhibitor titer. Disclosures: Manco-Johnson: Bayer HealthCare: Membership on an entity’s Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Baxter BioScience: Membership on an entity’s Board of Directors or advisory committees; Biogen Idec: Membership on an entity’s Board of Directors or advisory committees; Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees; Eisai: Research Funding. Maahs:Baxter BioScience: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Biogen Idec: Membership on an entity’s Board of Directors or advisory committees; Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Shapiro:Baxter BioScience: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Novo Nordisck: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Bayer Healthcare: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Biogen Idec: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Chugai Pharma: Consultancy; Kedrion Biopharma: Consultancy, Research Funding; Cangene Pharmaceuticals: Research Funding; CSL Behring: Research Funding; Octopharma: Research Funding; PTC Therapeutics: Research Funding; Eli Lilly: Research Funding.
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Fukutake, Katsuyuki, Manual Carcao, Aida Inbal, Bryce A. Kerlin, Johannes Oldenburg, Anders Rosholm, May-Lill Garly, and Diane J. Nugent. "New Data on the Safety and Efficacy of Recombinant FXIII in Patients with Congenital FXIII A-Subunit Deficiency." Blood 124, no. 21 (December 6, 2014): 1520. http://dx.doi.org/10.1182/blood.v124.21.1520.1520.
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Abstract Introduction Recombinant FXIII (rFXIII) represents a new treatment opportunity for patients with congenital FXIII A-subunit deficiency. Monthly prophylaxis with 35 IU/kg rFXIII was shown to effectively control bleeding with an annualized bleeding rate (ABR) of 0.138 bleeds requiring treatment per patient per year and an excellent safety profile (Inbal A, et al. Blood 2012;119:5111-7). PK analysis revealed first-order elimination of rFXIII with a geometric mean half-life of 13.6 days. All patients had a mean FXIII trough activity level of >0.1 IU/mL (Kerlin B, et al.JTH 2013;11:235). The PK profile was independent of age, supporting that monthly dosing with a fixed 35 IU/Kg rFXIII regimen for all patients with FXIII A-subunit deficiency (regardless of age) was adequate for prophylaxis (Brand-Staufer B, et al. Blood 2013;122:3613. Williams M, et al. Haemophilia 2014;20:99–105). Due to the novel nature of this recombinant molecule, a phase 3b safety extension program was offered to bridge to product availability, the extensive interim results of which are analyzed here. Methods The mentorTM2 trial is an ongoing safety extension trial to the pivotal mentorTM1 trial (Figure). All patients were dosed with 35 IU/kg rFXIII every 4th week. Figure. The Novo Nordisk clinical trial program for recombinant Factor 13 Figure. The Novo Nordisk clinical trial program for recombinant Factor 13 A planned interim analysis for mentorTM2 trial was performed (data cut-off: 31-DEC-2013). The Berichrom® FXIII activity assay was used for measurement of FXIII activity. Results Sixty patients have been enrolled into mentorTM2; baseline patient demographics are presented in the Table. Of these 60, 34 patients were enrolled from the mentorTM1 trial, and 26 new patients were enrolled. Table. Age, median (range) 26 (7-77) Age, mean (range) 31 (7-77) Male sex, n (%) 38 (63) Race, n (%) Black or African American American Indian or Alaska Native White Asian* Other Unknown** 6 (10)1 (2)34 (57)9 (15)6 (10)4 (7) Body Mass Index, median (range) 23.7 (12.8-36.9) Height in cm, median (range) 167.0 (131.0-187.5) Weight in kg, median (range) 67.5 (22.0-119.4) * Including 5 Japanese ** French patients are marked as unknown as per the French authorities guideline In mentorTM2, 60 patients had 2,157 exposures (monthly dosing), corresponding to a total of 168 patient years. The ABR was 0.042 bleeds/patient/year overall, 0.012 bleeds/patient/year for spontaneous bleeds, and 0.030 bleeds/patient/year for traumatic bleeds. In total 6 patients experienced 7 bleeds requiring FXIII treatment (5 trauma-induced and 2 spontaneous). Of these 7 bleeds, 1 trauma-induced muscular bleed was treated with rFXIII with excellent hemostatic response. No intracranial, internal organ or severe gastrointestinal bleeds occurred during the trial period. Mean FXIII trough levels were greater than 0.10 IU/mL in all patients. No thromboembolic events, fatal adverse events or adverse events leading to withdrawal were reported. Serious adverse events were few (16 events in 10 patients) and were evaluated by the investigators as unlikely related to trial drug. No anti-rFXIII antibodies were detected. Discussion Prophylaxis of bleeding of patients with congenital FXIII A-subunit deficiency with rFXIII in the mentor™ trials program has demonstrated very effective bleed control, with an excellent safety profile. The ABR in the ongoing mentorTM2 safety extension trial was 0.042, which is lower than the rate of 0.138 seen in the mentor™1 pivotal study. A bleeding rate of 0.042 corresponds to an average patient having 1 bleed approximately every 24 years. One patient who had a traumatic breakthrough bleed was treated with rFXIII with excellent outcome. These efficacy data, combined with comprehensive PK- and safety data, represent the largest data collection in congenital FXIII A-subunit deficiency in the world, and provide extensive evidence for the safety and efficacy of monthly prophylaxis with 35 IU/kg rFXIII. Disclosures Fukutake: Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxter: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Biogen Idec: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kaketsuken: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SRL, Inc: Consultancy; LSI Medience Corporation: Consultancy, Honoraria, Speakers Bureau; Chugai Pharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; TORII PHARMACEUTICAL CO., LTD.: Honoraria; Sekisui Medical CO., LTD: Honoraria, Research Funding, Speakers Bureau. Carcao:Baxter, Bayer, Biogen, Novo Nordisk, Pfizer, CSL Behring, Octapaharma : Honoraria, Research Funding, Speakers Bureau. Kerlin:Bayer HealthCare US: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Oldenburg:Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Rosholm:Novo Nordisk: Employment, Equity Ownership. Garly:Novo Nordisk: Employment, Equity Ownership. Nugent:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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Dhodapkar, Madhav V., Rachael Sexton, Antje Hoering, Bart Barlogie, and Robert Z. Orlowski. "African-American Patients with Monoclonal Gammopathy Have a Reduced Risk of Transformation to Clinical Myeloma: Results of a Prospective Study SWOG S0120." Blood 132, Supplement 1 (November 29, 2018): 1877. http://dx.doi.org/10.1182/blood-2018-99-119634.
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Abstract Introduction: Both multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are associated with marked racial disparities; incidence of both MM and MGUS is increased nearly 3-fold in African American (AA) compared to Caucasian/European American (EA) cohorts. Current estimates of the risk of progression to clinical malignancy in MGUS and asymptomatic myeloma (AMM) are at 1% and 10% per year respectively, based on data from EA cohorts such as from the Olmstead county in Minnesota. Risk estimates from prospective studies in AA cohorts are urgently needed to guide optimal management of these patients. Methods: Between 2003 and 2011, 331 eligible patients with IgG/A monoclonal gammopathy were enrolled in a prospective observational trial (SWOG S0120). All patients underwent uniform staging evaluation at baseline and follow up monitoring for progression to clinical myeloma (CMM). This analysis is focused on the impact of race on clinical and biologic features and risk of progression. Results: Of 331 eligible patients, 57 (17%) were of AA descent. Clinical features of the AA cohort were comparable to the non-AA counterparts, with the exception of higher proportion of females (61% versus 43%; p=0.01) and hemoglobin < 12 g/dl (37% versus 23%; p=0.04) in the AA cohort. Among 126 patients with available data on gene expression profile (GEP) of CD138-purified plasma cells, the proportion of patients with GEP-defined subsets was similar between AA and non-AA cohorts. The risk of transformation to clinical malignancy in AA patients was significantly lower than in non-AA cohort (2 year risk 5% vs 15%; 5 year risk 13% versus 24%; log rank p 0.04). Differences in risk were evident for both MGUS (2 year risk 0% versus 2 %) and AMM (2 year risk 13% versus 25%). The proportion of patients with high risk GEP signature (GEP-70 gene risk > -0.26) in purified tumor cells was markedly lower in the AA cohort (0% versus 33%, p=0.01). Unbiased analysis of which genes in the AA cohort predict risk of progression is ongoing. Conclusions: Together these data provide the first prospective evidence that AA patients with myeloma precursor states carry significantly lower risk of progression to CMM compared to non-AA counterparts. This may be explained in part by the finding that precursor lesions in AA patients have markedly lower proportion of genomic changes (such as GEP70-risk signature derived predominantly from chromosome 1) previously associated with higher risk of malignancy in EA cohorts. The mechanisms underlying the transformation to CMM may therefore differ between AA and EA cohorts, which in turn may impact optimal management of these patients. Disclosures Barlogie: Dana Farber Cancer Institute: Other: travel stipend; Celgene: Consultancy, Research Funding; ComtecMed- World Congress on Controversies in Hematology: Other: travel stipend; European School of Haematology- International Conference on Multiple Myeloma: Other: travel stipend; International Workshop on Waldenström's Macroglobulinemia: Other: travel stipend; Millenium: Consultancy, Research Funding; Myeloma Health, LLC: Patents & Royalties: : Co-inventor of patents and patent applications related to use of GEP in cancer medicine licensed to Myeloma Health, LLC; Multiple Myeloma Research Foundation: Other: travel stipend. Orlowski:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BioTheryX, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Poseida: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy; Millenium Pharmaceuticals: Consultancy, Research Funding.
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Siegel, Ariel, Eileen M. Boyle, Patrick Blaney, Yubao Wang, Hussein Ghamlouch, Jinyoung Choi, Jessica Caro, et al. "Unifying the Definition of High-Risk in Multiple Myeloma." Blood 138, Supplement 1 (November 5, 2021): 2714. http://dx.doi.org/10.1182/blood-2021-148502.
Full textAbstract:
Abstract Introduction: There is considerable heterogeneity in the clinical outcome of newly diagnosed multiple-myeloma (NDMM) with some patients having a good prognosis while others fail to respond or relapse quickly after therapy progressing rapidly to death. Using risk scores based on clinical, biochemical and genetic features it is possible to predict some of this variation giving an ability to segment the disease into risk strata. Clinical studies have suggested that patients with standard-risk disease have benefited more from the recent advances in therapy compared to those with high-risk disease. The development of clinical trials specifically recruiting patients with high-risk disease features offers the potential to improve the outcome of a subgroup of patients with a very poor clinical outcome. To perform such studies is it important to have a unifying definition of high-risk including standard parameters, group size and outcome of individual risk strata so that clinical trial rigor can be achieved (e.g., common entry criteria, statistical power). In order to understand the size and feasibility of such studies we analyzed the Myeloma Genome Project (MGP) dataset to assess multiple risk factors and scores to determine and compare how they perform as risk stratifiers with each other. Methods: The MGP dataset is a large set of molecular and clinical data from 1273 patient with NDMM. Data were available on clinical variables (Albumin (Alb), B2-microglobulin (B2M), LDH, age), cytogenetic variables [t(4;14), t(14;16), t(14;20), 17p-, TP53 mutations, 1q+ and 1p-] and gene expression analysis (GEP70). A literature search was used to identify risk models used in clinical studies. Survival analysis was performed in R. The median follow-up at the time of analysis was 54.5 (53.2-56.5) months. Results: The median patient age was 66 years, with 641 (50.4%) patients over age 65. The sex ratio (M:F) was 1:0.66. African American, White, and Asian constituted 17%, 76%, and 2%, of cases respectively. 26.7% received a stem cell transplant. We determined the size of the strata and actual risk (measure by the hazard ratios, HR) compared to standard risk cases for both PFS and OS of the various clinical models available, data are summarized in Figure 1. When looking at individual risk scores, the HR for progression for t(4;14), TP53 inactivation (deletion and mutations), gain(1q), and del(1p) were 1.4, 1.1, 1.3, and 1.1 respectively. When considering overall survival these HR were 1.4, 1.7, 1.5, and 1.4 respectively. We went on to analyze the impact of these events in combination and show that combined, there is increased specificity, especially for OS (HR 2.3-5.1) but they identify small subsets making up <10% of patients. We then analyzed the purely clinical scores (ISS) and combined clinical/genetic scores. We show again, that the more specific risk scores (double hit, Boyd IV, GEP70) identify between 7-13% of cases with HR (2-3.1) for OS. When we looked specifically at the younger patients (=< 65), similar trends were seen with GEP70 by RNA-seq offering one of the most interesting means of identifying HR cases. Conclusion: In this large NDMM dataset, we demonstrate the clear variation in risk groups that occur dependent upon the approach used resulting in heterogeneous levels of risk, strata size, and performance. With the exception of GEP70, none of the single features are sensitive or specific enough to identify all cases. Risk models based on a combination of markers improve the ability to detect true high-risk disease but there remains variability. At a molecular level the inclusion of TP53 inactivation, and 1q+ improve the performance of the ISS. This analysis provides insights into standardizing the definition of high-risk and the generation of consensus definitions for clinical trial entry. Figure 1 Figure 1 Figure 1. Disclosures Braunstein: Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Pawlyn: Celgene / BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cairns: Amgen: Research Funding; Merck Sharpe and Dohme: Research Funding; Takeda: Research Funding; Celgene / BMS: Other: travel support, Research Funding. Jackson: GSK: Consultancy, Honoraria, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; amgen: Consultancy, Honoraria, Speakers Bureau; celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; J and J: Consultancy, Honoraria, Speakers Bureau; oncopeptides: Consultancy; Sanofi: Honoraria, Speakers Bureau. Morgan: BMS: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees. Davies: Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Constellation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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Hood, Anna M., Aimee K. Hildenbrand, Joanna Rebitski, Jasmine Stallworth, Yolanda Johnson, Stacey Gomes, Catharine Whitacre, et al. "Effects of the COVID-19 Pandemic on Caregivers of Young Children with Sickle Cell Disease Enrolled in the Engage-HU Trial." Blood 138, Supplement 1 (November 5, 2021): 1891. http://dx.doi.org/10.1182/blood-2021-152722.
Full textAbstract:
Abstract Background: Hydroxyurea (HU) is the primary medication used to prevent the significant medical and neurologic morbidities of pediatric sickle cell disease (SCD; HbSS or HbSB0 thalassemia). Despite the benefits of HU, it remains under-utilized likely due to lack of clinician knowledge/training and negative caregiver perceptions. Thus, we developed the Engage-HU randomized controlled trial (NCT03442114) as a novel approach to address HU utilization barriers. Engage-HU is designed to assess how clinicians can engage caregivers in a shared discussion that considers their values, preferences, and scientific evidence about HU. The COVID-19 pandemic has resulted in significant changes to healthcare delivery for children with SCD, as they are at increased risk of severe illness from COVID-19 infection. Given their risk status, it was recommended that patients with SCD complete telehealth visits when possible. Some families also chose to delay care because they feared their child would get infected at hospitals/healthcare clinics that care for COVID-19 positive patients. Since the lives of all families enrolled in the Engage-HU trial have been affected to some extent, we incorporated measures to capture the impact of the COVID-19 pandemic and the usability of telemedicine implementation and services. Methods: Engage-HU is a randomized control trial comparing two dissemination methods for clinicians to facilitate shared decision-making with caregivers of young children with SCD. Study outcomes include caregiver confidence in decision-making and perceptions of experiencing shared decision-making as well as HU uptake and child health outcomes. Eligible children are 0 to 5 years, candidates for HU, and their caregiver has not decided about HU in the past 3 months. The trial is being conducted at 9 sites in the United States and uses a unidirectional crossover design. The primary endpoints are caregiver decisional uncertainty and caregiver perception of shared decision-making measured using validated tools. Data will be analyzed using the intent-to-treat principle, and all participants will remain in the arm to which they were randomized. A multiple group comparison analysis will be performed to assess significant response variable differences by group randomization. The Engage-HU study aims to recruit 174 caregivers who are considering initiating HU. The trial is being conducted at 9 sites in the United States. Data collection is ongoing, and 160 caregiver-participants have been enrolled to date. Since May 2020, caregiver-participants have completed the COVID-19 Exposure and Family Impact Scales (CEFIS), which contain 2 subscales (exposure to potentially traumatic aspects of the pandemic, impact on families), and the COVID-19 telemedicine use survey during a study visit. Results: Currently, 8 of the 9 sites have collected data from 48 caregivers (93.8% mothers), most of whom (93.8%) identify as African American/Black (see Figure 1). Correlations indicated that older caregivers experienced greater exposure (Mean = 7.0, SD = 4.1, range = 1-19) to potentially traumatic aspects of the pandemic (r = .31, p = .04). Distress related to COVID-19 varied widely across the sample, for both caregivers (Mean = 5.9, SD = 2.9, range = 1-10) and children (Mean = 4.1, SD = 3.4, range = 1-10). Scores on the telemedicine usability survey were generally high, indicating that caregivers are happy with the quality of care delivered via telehealth. However, caregivers (r = .30, p = .09) and children (r = .32, p = .07) experiencing more pandemic-related distress reported less satisfaction with telehealth. Conclusion: Although Engage-HU has resumed research operations, recruitment has not reached pre-pandemic targets, as fewer eligible patients are scheduled for routine care visits at SCD clinics. Our preliminary analyses suggest a significant continued impact of the pandemic on families and general satisfaction with the quality of healthcare delivered via telemedicine. These findings indicate that targeted screenings to identify and intervene for those who demonstrate more COVID-19 pandemic-related distress are needed. Figure 1 Figure 1. Disclosures Quinn: Forma Therapeutics: Consultancy; Aruvant: Research Funding; Novo Nordisk: Consultancy; Emmaus Medical: Research Funding. Yates: Agios Pharmaceuticals: Current Employment. Badawy: Sanofi Genzyme: Consultancy; Vertex Pharmaceuticals Inc: Consultancy; Bluebird Bio Inc: Consultancy. Thompson: bluebird bio, Inc.: Consultancy, Research Funding; Baxalta: Research Funding; Biomarin: Research Funding; Celgene/BMS: Consultancy, Research Funding; CRISPR Therapeutics: Research Funding; Vertex: Research Funding; Editas: Research Funding; Graphite Bio: Research Funding; Novartis: Research Funding; Agios: Consultancy; Beam: Consultancy; Global Blood Therapeutics: Current equity holder in publicly-traded company. Smith-Whitley: Global Blood Therapeutics: Current Employment. King: National Cancer Institute: Research Funding; National Heart, Lung, and Blood Institute: Research Funding; Health Resources and Services Administration: Research Funding; Global Blood Therapeutics: Research Funding. Meier: CVS Caremark: Consultancy; Forma Therapeutic: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Membership on an entity's Board of Directors or advisory committees; Novartis,: Other: Data Safety Monitoring Board membership; NHLBI: Other: Data Safety Monitoring Board membership; Global Blood Therapeutics: Other: Steering Committee membership, grant funding; CDC,: Other: grant funding; Indiana Department of Health: Other: grant funding . Tubman: Global Blood Therapeutics: Consultancy, Research Funding; Novartis Pharmaceuticals: Honoraria, Research Funding; Forma Pharmaceuticals: Consultancy; Perkin Elmer: Honoraria. Crosby: Forma Therapeutics: Honoraria; PCORI: Research Funding; HRSA: Research Funding; Global Blood Therapeutics Panel: Honoraria; Children's Hospital of Philadelphia: Honoraria; Professional Resource Exchange: Patents & Royalties: $30-$60 every other year; SCDAA: Honoraria; NHLBI: Other: Payment for review of LRP Proposals, Research Funding. OffLabel Disclosure: Hydroxyurea has been FDA approved for the treatment of sickle cell disease for patients ages 2 years and above but NHLBI and ASH Guidelines recommend it be offered to children as young as age 9 months.
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Knight, Thomas G., Myra Robinson, Michael R. Grunwald, Lauren M. Bohannon, Erin Blackwell, Jing Ai, Brittany Ragon, et al. "Patient Reported Financial Toxicity in Acute Leukemia." Blood 132, Supplement 1 (November 29, 2018): 4796. http://dx.doi.org/10.1182/blood-2018-99-119163.
Full textAbstract:
Abstract Background: Financial Toxicity (FT) is increasingly recognized as a major contributor to morbidity and mortality in a variety of cancers. Treatment of acute leukemia is associated with heavy healthcare utilization and high costs. The purpose of this study was to define rates, risk factors, and mortality implications for FT in patients with acute leukemia using patient reported data. Methods: All patients seen at the Levine Cancer Institute, a tertiary hospital-based leukemia practice, were surveyed prior to each visit over a six-month period. All patients were aged ≥18 years and were diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). The survey consisted of the PROMIS Global-10 measure and two questions from the COST measure. FT was defined as scoring 4 or less (maximum: 10) in agreement with the COST questions: "I know that I have enough money in savings, retirement, or assets to cover the costs of my treatment" and "I am satisfied with my current financial situation." Demographic data and disease characteristics were abstracted from the medical record. Model selection was carried out using logistic regression to identify factors impacting the incidence of financial toxicity. Correlation of numerical financial toxicity scores with PROMIS scores and with mortality data was assessed using linear regression. Results: Of the 106 patients, 58 (54%) met the definition of exhibiting FT. The factors associated with incidence of FT included: age, race, and insurance type. The odds of FT in those patients <65 years of age were 2.7 times the odds of FT in those ≥65, adjusting for race, insurance, and time since first treatment (95% CI: 0.884 - 8.438, p = .081). The odds of FT in African American patients were 4.3 times the odds of FT in Caucasian patients, adjusting for age, insurance, and time since first treatment (CI: 0.408 - 44.824, p = .150). The odds of FT in patients with Medicaid insurance were 14.2 times the odds of FT in patients with commercial insurance, adjusting for age, race, and time since first treatment (CI: 1.658 - 121.862, p = .106). Gender, distance from the hospital, type of acute leukemia, history of blood/marrow transplant, and history of relapsed disease were not found to be significant. There was a significant correlation for both the PROMIS global physical (p < .001) and mental (p < .001) scores with the FT score. Lower FT score (higher degree of FT) was associated with lower mental and physical scores. There was no statistically significant difference in survival between patients with FT scores >4 compared to patients with FT scores <=4; however, there was a trend toward decreased survival in those with lower FT scores (Figures 1 and 2). Conclusions: Patients with acute leukemia represent an extremely vulnerable population for financial toxicity with rates of distress even higher than other reported malignancies. Urgent interventions are indicated in this population. Disclosures Grunwald: Medtronic: Equity Ownership; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Janssen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees. Symanowski:Five Prime Therapeutics: Other: Data Safety Monitoring Board ; Boston Biomedical: Other: Data Safety Monitoring Board ; Eli Lily & Co: Other: Data Safety Monitoring Board; Immatics: Other: Data Safety Monitoring Board.
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Boothby, Aaron, Michael Evans, Radhika Gangaraju, Camila Masias, Aric D. Parnes, Meera Sridharan, and Marshall Mazepa. "Use of Preemptive Treatment for Immune Thrombotic Thrombocytopenic Purpura: A Matched Survival Analysis." Blood 138, Supplement 1 (November 5, 2021): 2084. http://dx.doi.org/10.1182/blood-2021-149984.
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Abstract Background: Immune Thrombotic thrombocytopenic purpura (iTTP) is a relapsing disorder, resulting from depletion of ADAMTS13. With the goal of preventing clinical relapse there has been considerable interest in ADAMTS13 monitoring and preemptive treatment. Indeed, preemptive treatment with rituximab has shown significant promise and is now included in the 2020 International Society on Thrombosis and Haemostasis (ISTH) treatment guidelines. Evaluation of long-term outcomes of ADAMTS13 based preemptive treatment have generally relied on limited numbers of historical controls which did not incorporate matching for known risk factors for relapse such as race, number of prior episodes, and immunosuppression. Our study aims to leverage the data in the United States Thrombotic Microangiopathy (USTMA) iTTP registry to compare the clinical relapse-free survival (RFS) intervals between iTTP patients treated preemptively based on ADAMTS13 level and those treated only for clinical relapse base on clinical and laboratory manifestations of iTTP. Methods: We carried out a retrospective study utilizing the multi-center cohort of patients with iTTP from the USTMA Consortium (spanning 1985-2019 and containing 780 participant records). We selected for patients with relapsing disease treated either preemptively based on ADAMTS13 level or for clinical relapse. Each preemptively treated episode was matched to up to five clinically relapsed episodes using covariate balancing propensity score nearest-neighbor matching by age, gender, race, prior relapse status, acute treatment, treatment center, and calendar year, with exact matching required for treatment center and prior relapse status. Time from prior episode to relapse was compared between preemptively treated episodes and matched controls using a Cox proportional hazards model weighted by the matching weights, including subclasses as a cluster, and using cluster-robust standard errors. Results: We identified 1068 episodes of iTTP. Of these. Thirteen participants accounting for a total of seventeen preemptive treatment episodes were included in the data set however, we included only the thirteen first uses of preemptive treatment to avoid selection bias. These were matched with 59 episodes treated for clinical relapse. Over 70% of the included participants in both groups were identified as black/African American. Distribution of immunosuppressive medications used in clinically relapsed cases were not significantly different than those used in preemptive treatment, and corticosteroids were the most frequently used. Demographic and treatment data before and after matching are included in Table 1. There was no significant difference in RFS between the groups, hazard ratio 0.63 (95% confidence interval 0.26-1.54), p=0.31. Conclusion: To our knowledge this is the first study to use matching controls to obtain a causal estimate of the effect of ADAMTS13 monitoring based preemptive treatment on RFS in iTTP. In contrast to previous work, we did not observe a significant increase in RFS in the preemptively treated group. It is possible that the limited number of preemptively treated episodes herein did not provide sufficient power to detect a difference. However, given the significant effect size that has been proposed, based on prior work, we suspect other factors may have also influenced this finding. Previous analysis of the USTMA iTTP registry has shown a higher incidence of relapse in African American participants. While the precise reason for this finding is not yet clear, it is worth considering that there may also be differential response to preemptive treatment. Our study highlights the importance of continued efforts to determine the generalizability and efficacy of ADAMTS13 monitoring based preemptive treatment in iTTP. Figure 1 Figure 1. Disclosures Gangaraju: Alexion: Consultancy; Sanofi Genzyme: Consultancy. Masias: Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees. Parnes: Sigilon: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Shire/Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; I-mAb: Consultancy; Sunovion: Consultancy; Genentech/Hoffman LaRoche: Research Funding; UniQure: Membership on an entity's Board of Directors or advisory committees; Aspa: Consultancy. Mazepa: Answering TTP Foundation: Research Funding; Sanofi Aventis: Other. OffLabel Disclosure: Rituximab, an anti CD20 monoclonal antibody will be discussed in relation to treatment of thrombotic thrombocytopenic purpura.
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Bussel, James B., Michael D. Tarantino, Victor S. Blanchette, Ashok Raj, Jenny Despotovic, Donald Beam, John Roy, Xuena Wang, Bhakti Mehta, and Melissa Eisen. "Safety and Efficacy of Long-Term Open-Label Dosing of Subcutaneous (SC) Romiplostim in Children with Immune Thrombocytopenia (ITP)." Blood 128, no. 22 (December 2, 2016): 3738. http://dx.doi.org/10.1182/blood.v128.22.3738.3738.
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Abstract Background: Children with ITP for ≥6 months who completed a romiplostim phase 1/2 or phase 3 parent study could enroll in an open-label long-term extension study, data from which is presented here. Methods: Patients enrolled at 28 sites in the US, Canada, Spain, and Australia. All patients received SC romiplostim once weekly. The initial dose was the final dose from the parent study or 1 µg/kg for patients previously receiving placebo, adjusted from 1−10 µg/kg to target platelet counts of 50−200×109/L. Incidence of adverse events (AEs) was the primary endpoint. Results: As of 24 Feb 2016, 66 patients entered the extension study; 65 received romiplostim for up to 6.2 years. At baseline, median (min-max) age was 11 (3-18) years; 56% were female; 61% were white, 14% African American, 14% Hispanic/Latino, 9% Asian, and 3% other; 9.1% had prior splenectomy. Median (min-max) baseline platelet count was 27.5 (2-458)×109/L. Median (min-max) treatment duration was 100 (5-321) weeks. Median (min-max) average weekly romiplostim dose was 4.8 (0.1-10.0) µg/kg, which included escalation to a stable dose; 19 patients started on 1 μg/kg. After ~week 200 (n ≤8 patients), the median dose was observed to fluctuate. All 65 patients received their doses per protocol >90% of the time; 18 patients missed ≥1 dose due to noncompliance for a total of 41 times. Reasons for discontinuing treatment (n = 22, 33%) included consent withdrawn (n = 8), required other therapy (n = 4), noncompliance (n = 3), administrative decision (n = 3), treatment no longer needed (n = 1), per protocol (n = 1), and AE (n = 2) (asthenia, headache, dehydration, and vomiting in one patient and anxiety in the other, per investigator, none of the AEs were treatment-related); 43 (65%) patients continued in the study. Fifty-two serious AEs occurred in 17 patients, 3 deemed treatment-related (anemia, epistaxis, and thrombocytopenia). Bleeding AEs occurred in 56 patients; 5 deemed treatment-related (gingival bleeding, petechiae, injection site bruising, injection site hematoma, and epistaxis). Bleeding AEs occurring in ≥10 patients included contusion (n = 30), epistaxis (n = 29), petechiae (n = 19), and gingival bleeding (n = 12). No thrombotic events were reported. There were no peripheral blood abnormalities to warrant a bone marrow examination. After sporadic platelet responses and negative antibody (Ab) results in the parent study, a patient left the extension due to a need for other therapies and was then identified to have anti-romiplostim neutralizing Ab which were not present on retesting 3 and 6 months later. No patients had anti-TPO neutralizing Ab. From week 2 on, median platelet counts remained >50×109/L; platelet counts were >100×109/L at most timepoints, despite an observed decrease in the median dose from 4-5 μg/kg to 2-3 μg/kg around week 160 (Figure). For 15 patients (23%), the first study week was the first week receiving romiplostim (previously these patients received placebo). Nearly all (94%, 61/65) patients had a platelet response (median platelet counts for a month ≥50×109/L); the mean (SD) % of months with a platelet response was 77% (33%). Most (72%, 47/65) patients had a platelet response ≥75% of the time and over half (58%, 38/65) of patients had a platelet response ≥90% of the time. Nine (14%) patients entered remission (Table), defined here as platelet counts ≥50×109/L for 24 weeks with no ITP treatments; these patients, 5 boys and 4 girls, none with prior splenectomy, had ITP for a median (min-max) of 5 (2-10) years and had received romiplostim for a median (min-max) of 1.6 (0.7-6.2) years. Fifty-eight (89%) patients (or caregivers) self-administered romiplostim. Twenty-three (35%) patients received rescue medications. Conclusion: Over 6 years of data from this ongoing open-label extension study of romiplostim in children with ITP show that >90% of children achieved a platelet response with romiplostim, most responding ≥75% of the time. The safety profile was overall tolerable, similar to that in past studies. Some children (9/66) with longstanding ITP entered remission after receiving romiplostim. Table Table. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Bussel: Symphogen: Membership on an entity's Board of Directors or advisory committees; Physicians Education Resource: Speakers Bureau; Immunomedics: Research Funding; Cangene: Research Funding; UpToDate: Patents & Royalties; Boehringer Ingelheim: Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Protalex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prophylix Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Momenta Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; Sysmex: Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; BiologicTx: Research Funding; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Tarantino:Biogen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Blanchette:Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Data safety monitoring boards , Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Data safety monitoring boards . Wang:Amgen Inc.: Employment, Equity Ownership. Mehta:Amgen Inc.: Employment, Equity Ownership. Eisen:Amgen Inc.: Employment, Equity Ownership.
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Dunn, Joe P. "The National Model League of Arab States." Political Science Teacher 3, no. 1 (1990): 19–20. http://dx.doi.org/10.1017/s0896082800000945.
Full textAbstract:
Among the excellent national simulations available—the Harvard Model UN, Cleveland Model UN, Howard University Model Organization of African States, etc., and several regional models—the best may be the National Model League of Arab States, held annually in March at American University in Washington, DC. Sponsored by the Arab League Information Center and the National Council on U.S.-Arab Relations, the Model (in its seventh year in 1989) imitates the League of Arab States, an organization founded in 1945 for the purpose of coordinating issues related to Arab development and cooperation.College and university student delegations represent the 22 member states of the Arab nation. As they debate, lobby, and caucus, students learn about the interplay of the state system, international and regional organization, intra-Arab cooperation and conflict, issues of the region, and superpower impact upon the area. As participants gain greater understanding of the culture, concerns, achievements, and problems of the Arab world, they shed stereotypes, question prejudices, and begin to appreciate another perspective on regional issues.The Model League consists of plenary sessions, five committees (political, economic, social and cultural, legal, and Palestinian affairs), and a summit conference of the League Council. The bulk of time is spent in the committee sessions, where students introduce, debate, and build coalitions in support of resolutions. In the process, they practice parliamentary procedure and sharpen forensic and bargaining skills. Faculty advisors evaluate the delegations and nominate individuals for awards.
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Campbell, Andrew D., Raffaella Colombatti, Biree Andemariam, Crawford John Strunk, Immacolata Tartaglione, Connie M. Piccone, Deepa Manwani, et al. "An Analysis of Racial and Ethnic Backgrounds within the Casire International Cohort of Sickle Cell Disease Patients: Implications for Disease Phenotype and Clinical Research." Blood 134, Supplement_1 (November 13, 2019): 2305. http://dx.doi.org/10.1182/blood-2019-127613.
Full textAbstract:
Introduction: Millions are affected by Sickle Cell Disease (SCD) worldwide with the greatest burden in sub-saharan Africa. Its origin thought to lie within the malaria belt of the world, SCD continues to affect thousands of lives worldwide partly due to the migration patterns of the human race to different continents. We created the Consortium for the Advancement of Sickle Cell Research (CASiRe) to better understand the different phenotypes of SCD and compare the clinical profiles of patients living in different environments through a validated questionnaire and medical chart review, standardized across 4 countries (United States[U.S.] United Kingdom[U.K.], Italy and Ghana). For this report, we recorded the multi-generational ethnic and racial background of 877 SCD patients across the CASIRE cohort for our final analysis. Methods: CASiRe included 6 sites in the U.S. (Univ. of Michigan, Rainbow Babies & Children's Hospital, Promedica Toledo Children's Hospital, Children's Hospital at Montefiore, Connecticut Children's Medical Center, Univ.of Connecticut Health Center), 2 in Ghana(Ghana Institute of Clinical Genetics, Pediatric SCD Clinic at Korle Bu Teaching Hospital), 2 in Italy( Univ. of Campania Luigi Vanvitelli, Univ. of Padua, Italy), and U.K.(Guys & St. Thomas Hospital, Evelina Children's Hosp). Between 2011 and 2017, after obtaining IRB approval at each site and written informed consent, demographic, clinical and laboratory data were collected by interviewing the patient and/or parent/guardian At the 2 sites (Guys and St Thomas Hospital, UK; Univ. of Padua, Italy) with existing IRB approved SCD registries data were abstracted directly from their respective databases. Descriptive statistics were performed on a subset of demographic data that included: age, race, gender, sickle cell genotype, country of birth of patient, parents, and grandparents. The geographic region and country of origin was based on parents' country of birth and separated into 10 regions: W.Africa, C.Africa, N Africa, Caribbean, C. America, N America, Europe, S America, Asia, Middle East. Results: 877 patients were enrolled with a median age 19.3 years. 451 (51.4%) patients were children, 424 (48.3%) male. Ghanaians represented 41.6% (365) of patients, while 254 patients (29%) were from the U.S. Italy enrolled 81 patients (9.2%), and 177 patients (20.2%) were from the U.K. West Africa represented the largest geographic region of origin of(577/65.8%), followed by N. America (184/21%), Caribbean (51/5.8%), Europe (27/3.1%), and Central Africa (24/2.7%). Overall(Fig. 1), 75% of patients (658) had Hgb SS, 168 patients (19.2%) had Sickle C disease, 29 (3.3%) had Sβ+thal and 22 patients (2.5%) of patients had Sβ0 thal. Racially, 820 patients (93.5%) identified themselves as African American or Black, while 30 patients (3.4%) identified themselves as Caucasian and 21 patients (2.4%) identified themselves as Latino or Hispanic. All Ghanaians identified as Black, while in the US and UK, over 90% of patients identified themselves as Black, and about 3% reported themselves as Caucasian. In comparison, in Italy, over 76% of patients reported a Black racial background, while 21% reported Caucasian background. (Table 1 and 2)>98%Ghanaian patients and their parents were born in Ghana. In contrast, 66.7% of patients and <15% of parents in Italian sites were born in Italy with the 64% of parents emanating from West Africa (38% Nigeria).Over 85% of patients in the UK were born in the UK while only 5.1% of parents were born there (54% in Nigeria). In the US, >90% of patients were born within the US; Parents of patients were born in America 70% of the time. Caribbean (12.5%) and West African countries(9.5%) were the next highest parent countries of origin. 32 different countries of origin were reported within our cohort with the US leading with 22 different countries. Conclusion: This study is the first to describe the geographic distribution of these migrations in a very large cohort of nearly 900 patients with SCD.West Africa represented the largest geographic region of origin for SCD patients in Europe while Caribbean was the leading Non-US geographic region of origin in American patients. The diverse ethnic backgrounds observed in our cohort raises the possibility of how genetic and environmental heterogeneity within each SCD population subgroup can have implications on the clinical phenotype and clinical research outcomes. Disclosures Campbell: Novartis: Research Funding; Cyclerion: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding. Colombatti:Novartis: Consultancy; Global Blood Therapeutics: Consultancy; AddMedica: Consultancy. Andemariam:NovoNordisk: Membership on an entity's Board of Directors or advisory committees; New Health Sciences: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Other: DSMB Member; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; Cyclerion: Membership on an entity's Board of Directors or advisory committees; Imara: Research Funding; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Community Health Network of Connecticut: Consultancy; Terumo BCT: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Strunk:Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Speakers Bureau. Piccone:Hemex Health, Inc.: Patents & Royalties. Manwani:GBT: Consultancy, Research Funding; Novartis: Consultancy; Pfizer: Consultancy. Perrotta:Novartis: Honoraria, Research Funding; Acceleron Pharma: Research Funding.
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Desai, Rishi J., Mufaddal Mahesri, Raisa Levin, Denise Globe, Krista McKerracher, Alex Mutebi, Rhonda Bohn, Maureen Achebe, and Sebastian Schneeweiss. "Clinical Outcomes and Healthcare Utilization in Patients with Sickle Cell Disease: A Nationwide Cohort Study of Medicaid Beneficiaries." Blood 134, Supplement_1 (November 13, 2019): 3459. http://dx.doi.org/10.1182/blood-2019-130373.
Full textAbstract:
Introduction: There is limited contemporary evidence on clinical outcomes and healthcare use in sickle-cell disease (SCD) patients enrolled in US Medicaid. We aimed to provide contemporary estimates for rates of vaso-occlusive crises (VOC), mortality, and healthcare resource utilization (HRU) in SCD patients enrolled in US Medicaid. Methods: We conducted a cohort study using nationwide Medicaid insurance claims data (2000-2013). Patients were included based on ≥1 inpatient or ≥2 outpatient HbSS SCD diagnosis claims after 365 days continuous enrollment in Medicaid (or continuous eligibility since birth if age at diagnosis is <1 year). Patients were followed until Medicaid disenrollment, death, bone marrow transplant, or end of data availability (December 31, 2013). Outcomes included frequency of VOCs, event rates of HRU including emergency department (ED) visits, hospitalizations, outpatient visits, and blood transfusions, and all-cause mortality during the follow-up period. All outcomes were reported as annualized event rates (with 95% confidence intervals). VOCs were stratified by age-group (<1, 2-6, 7-12, 13-18, 19-35, 35+ years), VOCs at baseline (<2, 2-4, >=5), race (African American or not), and sex. The impact of VOCs on the risk of mortality was analyzed using an extended multivariable Cox model with VOCs modeled as time-varying and updated annually. Results: A total of 44,033 SCD patients were included in the analysis; 47% were female, 82% were African American, and a mean (SD) age of 15.7 (13.6). The average VOC rate was 3.71 (95% CI: 3.70-3.72) VOCs per person-year over an average follow-up period of 4.3 years. The rate of VOCs was substantially higher among patients aged 19-35 years and those with a higher VOC frequency at baseline (Table 1). Overall, the event rates (95%CI) per person year for other HRU outcomes were: 2.97 (2.97-2.98) ED visits, 2.39 (2.38-2.40) hospitalizations, 5.80 (5.79-5.81) outpatient visits, and 0.91 (95%CI: 0.90-0.91) blood transfusions. The mortality rate was 1.13 (95%CI: 1.08-1.17) events per 100 person-years overall, with the highest rate being 4.91 (95%CI: 4.58-5.25) events per 100 person-years among patients ≥ 35 years of age. Higher VOC burden in the preceding year was associated with an increased risk mortality: 2-4 VOC vs. 0 or 1 VOC: Hazard Ratio (HR)=1.36 (95%CI: 1.21-1.52); ≥ 5 VOC: HR= 1.56 (95%CI: 1.39-1.75). Conclusion: The burden of SCD in US Medicaid enrollees is substantial, especially during early adulthood, with markedly high rates of VOCs, mortality, and healthcare utilization. A higher VOC rate in the preceding year was associated with an increased risk of mortality suggesting a need for careful management of SCD patients with higher VOC burden. Table 1. Annualized rates of vaso-occlusive crises (VOC) among sickle cell disease patients enrolled in Medicaid. VOC, vaso-occlusive crises; CI, confidence interval. Table 1 Disclosures Desai: Merck: Research Funding; Bayer: Research Funding. Globe:Vertex Pharmaceuticals Incorporated: Employment. McKerracher:CRISPR Therapeutics: Employment. Mutebi:Vertex Pharmaceuticals Incorporated: Employment. Bohn:Bohn Epidemiology: Equity Ownership; Vertex Pharmaceuticals Inc: Consultancy. Achebe:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Fulcrum Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees. Schneeweiss:Genentech: Research Funding; Boehringer Ingelheim: Research Funding; Aetion, Inc.: Consultancy, Equity Ownership; Whiscon LLC: Consultancy.