Real-world outcomes of venetoclax-based therapy vs intensive chemotherapy in older adults with newly diagnosed Acute Myeloid Leukemia

Abstract Title: Real-World Outcomes of Venetoclax-Based Therapy vs Intensive Chemotherapy in Older Adults With Newly Diagnosed Acute Myeloid Leukemia Background: Venetoclax in combination with hypomethylating agents (HMAs) has emerged as a low-intensity frontline treatment for older or unfit patients with acute myeloid leukemia (AML). However, real-world comparisons to intensive chemotherapy in this population remain limited. Understanding the trade-offs between efficacy and tolerability is essential for optimizing treatment decisions in older adults. This study aims to compare real-world clinical outcomes, including survival, infectious complications, and cytopenic events, among older AML patients treated with Venetoclax-based regimens versus intensive chemotherapy. Methods: We conducted a retrospective cohort study using the TriNetX, a US Nationwide de-identified database. Adults aged ≥60 with newly diagnosed AML who initiated either Venetoclax + HMA or intensive chemotherapy (cytarabine plus an anthracycline) within 30 days of diagnosis were included. Patients were excluded if they received both regimens, had prior AML-directed therapy, or had a diagnosis of acute promyelocytic leukemia. Propensity score matching (1:1) was performed based on demographics and comorbidities including hypertensive diseases, ischemic heart disease, chronic kidney diseases, and diabetes mellites. Outcomes included 30- and 90-day mortality, infection within 60 days, antineoplastic-induced pancytopenia, and overall survival (OS). Statistical analyses included logistic regression for binary outcomes and Cox proportional hazards modeling for OS. Results: Propensity score matching resulted in 380 matched patients per treatment arm. In the matched cohort, Venetoclax-based therapy was associated with a significantly lower incidence of infections within 60 days compared to intensive chemotherapy (36.5% vs 48.6%; p = 0.0003), as well as a reduced rate of antineoplastic-induced pancytopenia (48.4% vs 56.5%; p = 0.0166). There were no significant differences in 30-day mortality (12.2% vs 14.7%; p = 0.27) or 90-day mortality (28.7% vs 25.5%; p = 0.28) between the two groups. However, median OS was significantly longer among patients treated with intensive chemotherapy (482 vs 246 days), with a hazard ratio of 0.674 (95% CI: 0.561-0.809; p < 0.0001). Conclusion: In this large, real-world matched cohort of older AML patients, Venetoclax-based therapy was associated with reduced early infectious and cytopenic complications, but shorter overall survival compared to intensive chemotherapy. These findings highlight the therapeutic trade-offs between tolerability and efficacy in older adults with AML and underscore the importance of individualized treatment decisions.