ALBERT

Description: Introduction: Rivaroxaban is a target specific oral anticoagulant approved for treatment of deep venous thromboembolism (DVT), pulmonary embolism (PE) and risk reduction in patients with DVT/PE requiring continued anticoagulation. The XALIA study showed a reduced bleeding risk compared to standard anticoagulation therapy; however, there is paucity of data regarding correlates of bleeding risk amongst patients receiving rivaroxaban in the community setting. We aimed to investigate the clinical factors associated with bleeding events (BE) in patients receiving rivaroxaban for treatment of DVT/PE. Methods: A retrospective study was conducted at John H. Stroger, Jr. Hospital of Cook County. We screened the charts of 837 patients who received rivaroxaban from January 1, 2015 to April 01, 2018. Patients with DVT/PE were included in the study (n=271). Patients with atrial fibrillation and those receiving rivaroxaban for prophylaxis were excluded. Any reported BE was recorded as either major or minor bleeding event. Major BE was defined as events requiring hospitalization, blood transfusions or significant drop in hemoglobin (〉2gm/dL). Rest of the BE were classified as minor BE. Socio-demographic and clinical factors were collected. Chi-square test and fisher exact test were used as the tests of trend. Multivariate logistic regression models were used to quantify the independent predictors. Odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. Results: The study included 271 patients, of which 68.3% were African-American, 14.4% were Caucasian, and 12.9% were Hispanic. Median age was 53 years and 60.9% patients were men. Bleeding events were reported in 11.4% (n=31) patients with 6.3% major bleeding events and 5.2% minor bleeding events. Only concurrent use of aspirin (23.8% vs. 9.2%; OR 3.10, 95% CI 1.34-7.17, P = 0.008) was significantly associated with bleeding events. None of the clinical parameters, like abnormal liver function tests (11.4%), cirrhosis (3.3%), chronic kidney disease stage 3 or worse (7.6%), prior use of warfarin (29.9%) or low molecular weight heparin (18.1%) were associated with bleeding events. In multivariate model adjusted for age, gender and race, concurrent use of aspirin (aOR 3.06, 95% CI 1.23-7.62, P = 0.017) remained independent predictor of bleeding events. Conclusion: In the community practice, aspirin (81mg or 325mg) is prescribed for cardio-protection. A recently concluded trial showed a better cardioprotective effect of combining rivaroxaban and aspirin, without increase in BE in patients with stable cardiovascular disease. However, such data is not evident in patients receiving rivaroxaban for DVT/PE. Our study shows an increased rate of bleeding events in such patients with concurrent use of aspirin. Our study population comprises of two-third African-American patients who are under-represented in the clinical trials. Based on our results we would suggest further investigation in safety of prescribing aspirin with rivaroxaban in patients with DVT/PE in prospective trials. Disclosures No relevant conflicts of interest to declare.

Description: Background: Non-Hispanic Black (NHB) and Hispanic patients with Acute Myeloid Leukemia (AML) have higher mortality rates than non-Hispanic white (NHW) patients despite a lower incidence of disease, more favorable genetics and younger age at presentation (Patel. AJCO 2015). It is unknown whether these disparities are linked to disease biology or treatment approach. Prior large database analyses have suggested that differences in AML outcomes may be impacted by socioeconomic factors such as insurance status and household income but lack data regarding treatment details including complications and molecular disease features (Bhatt. Blood Advances 2018). We postulate that increased mortality rates for NHB and Hispanic patients with AML are driven by disparities in treatment patterns when adjusted for baseline disease risk. Methods: We have analyzed data collected on consecutive adult patients diagnosed with AML between 2012 and 2018 from 5 academic cancer centers in Chicago surveying different population subsets using an IRB approved protocol. Figure 1 shows insurance status of the patient cohort by zip code. Cox proportional hazards models will be used to estimate multivariable-adjusted hazard ratios for relapse and mortality. Baseline models will be adjusted for age, gender and race/ethnicity to estimate the hazard ratios for the NHB-NHW and Hispanic-NHW disparities in time to relapse and treatment-related or disease-related mortality. Results: At the time of abstract submission 263 subjects were included in the analysis. The study is actively accruing at all 5 institutions with a database goal of 700 patients. There are significant differences in baseline characteristics by race/ethnicity (Table 1). NHB patients are younger, less likely to be married, and less likely to be privately insured than NHW (20% vs 〉51%). Hispanic patients are younger and more likely to be uninsured than NHW patients (30% vs 6%), likely reflective of County Hospital patients. In this preliminary dataset, clinical trial enrollment rates were similar by race/ethnicity. The distribution of ELN risk groups (Dohner. Blood 2017) and therapy-related AML (t-AML) cases were also similar by race/ethnicity. Eighty percent of patients received intensive induction chemotherapy (Fig 2). Receipt of intensive therapy did not differ by race but was more prevalent in younger patients and uninsured patients (Table 2), likely related to concerns about outpatient medication coverage. Elderly, adverse ELN risk and t-AML patients were less likely to receive intensive chemotherapy, likely due to poorer performance status in the elderly and potential chemo-resistance in p53mut AML. Treatment complications during induction chemotherapy, as captured by ICU admissions, were significantly lower in NHW patients, and significantly increased in morbidly obese patients. Treatment failure, by IWG criteria, did not differ by race but rather was determined by disease specific factors including ELN group, and t-AML. Relapse risk was higher in FLT3-ITD mutant cases. Allogeneic transplant rates did not differ significantly by race but were higher in adverse ELN groups and in privately insured patients. Two-year survival was affected by individual and disease specific factors including age, Medicare enrollment, t-AML and ELN risk group. Discussion: Our current dataset (n = 263) highlights disparities in treatment approaches in patients with AML. These include i) the preferential utilization of intensive induction chemotherapy in younger patients and those lacking high risk molecular features, and ii), the influence of payer status and molecular risk on utilization of allogeneic stem cell transplant in first remission. Treatment outcomes in AML were also impacted by patient age, morbid obesity, marital status, and payer source in addition to known prognostic disease-specific factors (ELN risk group and t-AML). This large multi-institutional study has advantages over population-based registries (SEER, NCDB) through incorporation of molecular characteristics, treatment responses and tolerability data not available in public datasets, which can provide insight into biologic intermediates contributing to disparities. Ongoing analyses will examine how variables such as the comorbidity index and measures of socioeconomic status interact with molecular risk factors to determine outcomes in this diverse patient population. Disclosures Stock: Research to Practice: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria. Galvin:Incyte: Consultancy. Altman:prIME Oncology: Speakers Bureau; PeerView: Speakers Bureau; Theradex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Glycomimetics: Consultancy, Honoraria, Other: Data Safety and Monitoring Committee; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cancer Expert Now: Consultancy; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; France Foundation: Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Biosight: Other: US Lead. Quigley:Alexion: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; TEVA: Research Funding. Khan:Amgen: Consultancy; Celgene: Consultancy; Incyte: Honoraria; Pfizer: Consultancy; Takeda: Research Funding.

Description: Background: Non-Hispanic Black (NHB) and Hispanic patients with Acute Myeloid Leukemia (AML) have higher mortality rates than non-Hispanic white (NHW) patients despite lower incidence, more favorable genetics, and a younger age at presentation (Darbinyan, Blood Adv. 2017). We performed a multilevel analysis of disparities in AML patients to investigate the contribution of structural violence, specifically neighborhood SES, on racial/ethnic differences in leukemia-specific survival. Methods: Adult AML (non-APL) patients diagnosed between 2012 and 2018 at six academic cancer centers in the Chicago area were included. Census tract data was collected using the FFIEC Geocoding/Mapping System and computed tract disadvantage and tract affluence scores were categorized into distribution tertiles (low, moderate, high). Time to relapse and death from leukemia were examined, adjusting for age, gender and race/ethnicity (baseline models), and for potential mediators of racial disparities including distal (Charlson Comorbidity Index (CCI), obesity, concentrated disadvantage and affluence, health insurance status), and proximal mediators (somatic mutations, and European Leukemia Network (ELN) prognostic score categories). Results Patient characteristics are shown in Table 1 (n = 822). Significant heterogeneity in age and comorbidities at diagnosis was observed, with Hispanic patients being the youngest and with the lowest CCI. Morbid obesity was more prevalent in NHB and Hispanic (23% and 20%, respectively) compared with NHW (11%) patients. Payer source also differed significantly; private insurance was twice as frequent among NHW than NHB (51% vs. 25%) patients, while the largest uninsured population was Hispanic. ELN adverse risk disease was most prevalent in NHW subjects, NPM1 mutations were least prevalent in Hispanic patients, and p53 mutations more prevalent in NHB (26%) compared to NHW (12%) and Hispanics (9%) although due to low numbers this did not reach significance (p=0.10). NHB and Hispanic patients tended to reside in more disadvantaged and less affluent areas. Treatment data was available for 764 patients (Table 2); 75% received intensive induction therapy and choice of first-line treatment did not differ by race or tract disadvantage. Allogeneic transplant rates however differed by race, age, insurance status, tract disadvantage, and ELN score. Treatment complications of induction chemotherapy, as reflected by ICU admissions during induction, were significantly lower in NHW (25%) compared to NHB (39%) and Hispanic (42%) patients. ICU admission rates were significantly higher in patients with morbid obesity and low tract affluence. Minority (vs. NHW) ethnicity was associated with a 42% increased hazard of death from leukemia (HR=1.42, 95% CI: 1.09, 1.85), and a 36% increased hazard of death from all causes (HR=1.36, 95% CI: 1.07, 1.72), each after controlling for age, gender and study site. Adjustment for continuous tract disadvantage and affluence and their interaction lowered both the hazard of leukemia and all cause death to 1.18 (95% CI: 0.88, 1.60) and 1.14 (95% CI: 0.88, 1.49), respectively. In formal mediation analysis, neighborhood SES accounted for 37% (p=0.09) and 50% (p=0.02) of the racial disparity in death from leukemia and all causes, respectively. Discussion: This study is the first to integrate data at the individual patient level with neighborhood characteristics, using census tract level variables to examine their contribution to AML patient outcomes. To date, formal mediation methods had not been employed to disentangle race/ethnic disparities in adult AML survival. Notably, our mediation analysis shows that census tract level SES explains a substantial proportion of the disparity in hazard of leukemia death. In addition, the observed disparities in treatment complications of induction chemotherapy, as reflected by ICU admissions, and the continued disparity in allogeneic transplant utilization all warrant further study. These results draw attention to the need for deeper investigation into the social and economic barriers to successful treatment outcomes for leukemia patients and represent an important first step toward designing strategies to mitigate these persistent health inequities. Disclosures Altman: Janssen: Consultancy; Syros: Consultancy; Genentech: Research Funding; Novartis: Consultancy; Amphivena: Research Funding; Amgen: Research Funding; Aprea: Research Funding; ImmunoGen: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; Fujifilm: Research Funding; Kartos: Research Funding; AbbVie: Other: advisory board, Research Funding; Kura Oncology: Other: Scientific Advisory Board - no payment accepted, Research Funding; BioSight: Other: No payment but was reimbursed for travel , Research Funding; Daiichi Sankyo: Other: Advisory Board - no payment but was reimbursed for travel; Agios: Other: advisory board, Research Funding; Glycomimetics: Other: Data safety and monitoring committee; Astellas: Other: Advisory Board, Speaker (no payment), Steering Committee (no payment), Research Funding; Theradex: Other: Advisory Board; Immune Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy; France Foundation: Consultancy; PeerView: Consultancy; PrIME Oncology: Consultancy; ASH: Consultancy; Cancer Expert Now: Consultancy. Stock:Research to Practice: Honoraria; UpToDate: Honoraria; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Society of Hematology: Honoraria; Leukemia and Lymphoma Society: Research Funding; Novartis: Research Funding; Abbvie: Honoraria, Research Funding; Morphosys: 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; Kite: 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; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Quigley:Alnylam: Speakers Bureau; Agios: Speakers Bureau; Amgen: Other: Advisory board. Khan:Celgene: Consultancy; Incyte: Honoraria; Takeda: Research Funding; Amgen: Consultancy.