Optimizing venetoclax duration with hypomethylating agents for newly diagnosed acute myeloid leukemia: impact on response and survival

The addition of venetoclax to hypomethylating agents (HMAs) is standard for older adults with newly diagnosed acute myeloid leukemia (AML). However, prolonged venetoclax (VEN) exposure can cause cytopenias and infections, raising questions about optimal duration. We conducted a single‑center retrospective study of 102 patients treated between 2018 and 2025 with azacitidine or decitabine plus VEN administered for 14 (n = 22), 21 (n = 48), or 28 (n = 32) days per 28‑day cycle. Baseline cytogenetic and molecular profiling, responses by 2022/2024 ELN criteria, measurable residual disease (MRD), cumulative incidence of relapse (CIR), disease‑free survival (DFS), and overall survival (OS) were analyzed using competing‑risks regression and Cox models. Median age was 68 years and patients received a median of 4 cycles. Composite remission (CR/CRi/CRh/MLFS) was 66.7%, with MRD negativity in 75.0% of responders. Remission and MRD negativity rates did not differ significantly across VEN‑duration cohorts. Median OS and DFS were 17.3 and 12.3 months, respectively, with no significant differences in OS, DFS, and CIR between 14‑, 21‑, and 28‑day cohorts. Grade ≥ 3 cytopenias and transfusion independence rates also did not differ significantly. In this cohort, shortening VEN exposure to 14 or 21 days did not show a significant difference in response, survival, relapse risk, and toxicity profiles relative to a 28‑day schedule in our cohort. These findings support further prospective evaluation of reduced VEN durations in this population.