Psychiatric and substance use disorders predict poor outcomes in older Veterans with acute myeloid leukemia

Abstract: Venetoclax-based therapies combined with either a DNA methyltransferase inhibitor or low-dose cytarabine have become the standard frontline treatment for older or unfit adults with acute myeloid leukemia (AML). However, real-world outcomes often fall short of those reported in clinical trials, with limited investigation into the role of psychiatric and substance use disorders (SUDs), especially in vulnerable populations such as veterans. Leveraging the Veterans Affairs (VA) Corporate Data Warehouse, a nationally integrated electronic health record (EHR) system, we conducted a retrospective cohort study of 452 veterans diagnosed with AML and treated with venetoclax-based regimens between 2018 and April 2022. Veterans, a frail population with unique wartime exposures, showed high prevalence of psychiatric disorders (46%) and SUDs (19%), with younger veterans disproportionately affected. These comorbidities were associated with significantly worse outcomes, including lower remission rates (38% for SUDs vs 57% overall), higher early mortality (35% for SUDs vs 13% for neither condition), and inferior overall survival. Multivariable analyses confirmed psychiatric disorders and SUDs as independent predictors of poor outcomes, even after adjusting for age, frailty, and AML-specific risk factors. The VA EHR system enabled detailed tracking of comorbidities, treatment patterns, and outcomes, highlighting the underrepresentation of veterans with psychiatric disorders and SUDs in clinical trials and the need for tailored interventions in this population. These findings underscore the importance of leveraging comprehensive EHR data to bridge gaps between clinical trial expectations and real-world outcomes while addressing the unique vulnerabilities of veterans with AML. Prospective studies are needed to explore mechanisms and interventions to improve care for this underrepresented group.