Racial/ethnic disparities in acute myeloid leukemia survival in the novel therapy era: an exploration of the underlying mechanisms and potential targets for intervention

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PROJECT SUMMARY The approval of venetoclax/azacitidine frontline therapy in November 2018 shifted the long-lived paradigm of “7+3”-based induction therapy and marks the new era of modern AML care. The development of novel targeted therapies substantially improves the outcomes for some patients and offers less intense treatment options to many in the outpatient and/or local setting. Along with the revolutionary changes in management strategies, the impact of racial/ethnic disparities has been increasingly recognized in AML, which may potentially be related to the differences in disease biology, but also due to disparity in socioeconomic status and the long-term impact of structural racism. New challenges on appropriate testing, response/toxicity monitoring, therapy adjustment and social support arise with the wide adoption of novel therapeutic agents, threatening to further widen the disparities in AML care. Currently, little is known about the magnitude and mechanisms of the impact of racial/ethnic disparities on AML survival in the novel therapy era. To begin to address these knowledge gaps, we will perform a retrospective cohort study using data from Flatiron Enhanced Datamart, a nationwide database uniquely featuring a diverse patient population, comprehensive pathological and molecular data, and excellent data recency. In our first Aim, we will assess the disparities in overall survival (OS) between 1) NHB and NHW patients and 2) Hispanic and NHW patients with newly diagnosed AML in the pre- and post-novel therapy era, respectively, to demonstrate the previously unknown OS disparities specifically in modern AML care. In our second Aim, we will assess the mechanisms of OS disparities in modern AML care by decomposing the total effects and exploring the causal pathway of racial/ethnic disparities in AML OS using modern causal mediation analysis. In Aim 2a, we will first perform a descriptive analysis to assess the differences of baseline AML genetic profiling across racial groups. Finding(s) in Aim 2a, along with other biological and non-biological variables, will then be evaluated as potential mediators of AML OS disparities in Aim 2b. Ultimately, the second Aim will provide important insight into the observed OS disparities in modern AML care and help identify potential targets for intervention to make more meaningful advances towards the mitigation of such disparities. These results will help understand the disparities and highlight the specific challenges racial minority groups are facing in modern AML care so that subsequent studies and interventions can be improved for this patient population. In addition, the training provided by this award will afford the applicant with skills important for her development into an independent investigator in the field of leukemia and myeloid malignancies. The proposed training plan includes advanced epidemiologic and biostatistical coursework in the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, as well as mentorship from researchers in epidemiology, biostatistics, and the Division of Hematology/Oncology.