Psychiatric Disorders, SUDs Diminish Venetoclax Outcomes in Veterans With AML

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Research results demonstrate that substance use and psychiatric disorders have a negative effect on mortality among veterans with AML receiving venetoclax.

Psychiatric and substance use disorders (SUDs) hinder remission and survival rates among military veterans taking frontline venetoclax-based combinations for acute myeloid leukemia (AML), according to a retrospective cohort study of Veterans Affairs data presented at the ASH Annual Meeting 2023.

“Psychiatric and substance use disorders are prevalent among veterans with AML and associated with lower likelihood of remission, higher incidence of ICU admissions after initiating venetoclax therapy, and higher hazards of early and overall mortality,” reported lead study author Michelle Hyunju Lee, MD, of Massachusetts General Hospital, Harvard medical School, and the VA Boston Healthcare System, in Boston, Massachusetts. 

“Potential mechanisms for the worse outcomes in our patients with these comorbidities include difficulty adhering to treatment or greater delays between standard treatment cycles, reemergence of their psychiatric disorders or substance dependence with a new cancer diagnosis, or distinct biologic mechanisms associated with these comorbidities,” she explained.

The median age for people with newly diagnosed AML is 69 years. Since 2018, venetoclax combinations have become the standard-of-care frontline treatment for patients aged 75 years or older, or who are younger than 75 but deemed unfit for intensive chemotherapy, Dr Lee said.

But Venetoclax remains a relatively novel treatment in clinical practice, and clinicians are still learning which patients benefit most from these combinations. 

Outcomes in the real-world setting have been inferior to those in clinical trials, Lee noted. Older adults have comorbidities, and it is not yet clear how many of them affect treatment outcomes.

Veterans represent an aging population with distinct health issues, Dr Lee said. Her team previously identified disparities in outcomes between veterans with AML and clinical trial populations. The team undertook the new study to determine the prevalence and impact of psychiatric disorders and SUDs on outcomes for AML treated upfront with venetoclax. 

In a cohort of 452 veterans with AML treated at Veterans Administration hospitals, 157 (35%) had a psychiatric disorder diagnosis, 34 (7.5%) had SUD, and 49 (11%) had both. One-third had anxiety diagnoses and 20.1% had posttraumatic stress disorder (PTSD). One hundred and forty-four (31.9%) had depression. Fourteen (3.1%) had schizophrenia or related psychotic disorders. Approximately 11% each had alcohol use or drug use disorders. The median age of the cohort was 74 years, “with age skewing younger for veterans with substance abuse.” Nearly all patients (98.5%) were male and 75.9% were white. 

No significant differences in AML progression were observed between subgroups, but SUD was associated with lower composite complete remission (CCR) rates (P =.003) and higher ICU hospitalization after induction (relative risk, 2.26; 95% CI, 1.56-3.2; P <.001). Within 60 days of venetoclax initiation, 87 (19%) of the cohort died. Veterans with SUD had the highest early mortality rates (35% vs 13% for patients with neither SUDs nor psychiatric diagnoses; P =.006).

In multivariate analyses, venetoclax response rates were lower for patients with both SUDs and psychiatric disorder diagnoses, and early mortality and overall mortality were higher. 

“The median overall survival [for the entire cohort] was 216 days, which is roughly 7 months,” Dr Lee said. “Psychiatric and substance use disorders were independently associated with lower odds of achieving a response, and veterans with psychiatric diagnoses were 2 times more likely to die within 60 days of starting venetoclax and had a 28% higher hazard of death compared to those without a psychiatric disorder.”

Additional research to better understand the mechanisms underlying these associations are underway, she said.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Lee MH, La J, Brophy MT, et al. Psychiatric and substance use disorders are independent predictors of treatment response and outcomes in United States veterans with newly diagnosed acute myeloid leukemia treated with venetoclax combinations. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 388.