Azacitidine plus low-dose venetoclax in elderly newly-diagnosed unfit AML: efficacy, safety, and implications for dose optimization

To evaluate efficacy, survival outcomes and clinical value of dose optimization with reduced-dose azacitidine (AZA)-venetoclax (VEN, VA) regimen in elderly newly diagnosed acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. This single-center retrospective analysis enrolled 32 unfit elderly AML patients treated between January 2021 and March 2025. The reduced-dose regimen comprised subcutaneous AZA 75 mg/m² daily on days 1–5 plus oral VEN 100 mg daily initially administered days 3–16, with VEN duration dynamically adjusted by day-17 bone marrow blast burden. VEN was prolonged to day 28 for blasts ≥ 10%; for blasts < 10%, VEN was discontinued in hypoplastic marrow or extended to day 28 in normocellular marrow. Median follow-up reached 7.3 months, with median overall survival (OS) of 12.3 months and median progression-free survival (PFS) of 10.1 months. The cycle-1 composite complete remission (CRc, CR + CRi) rate hit 81.3%, with MRD-negative rate of 43.8%; cycle-2 CRc and MRD negativity elevated to 84.4% and 65.6%, and the cumulative induction CRc reached 87.5%. Hematologic toxicities were controllable: grade ≥ 3 thrombocytopenia occurred in 37.5% and febrile neutropenia in 43.8%. Thirty-day mortality was 0%, while 60-day mortality stood at 6.3%. Notably, 40.6% of patients avoided platelet transfusion during induction, even with baseline platelet counts as low as 29 × 10⁹/L without prophylactic interventions. Response-adapted reduced-dose VA regimen achieves rapid, deep remission with acceptable safety, superior tolerability and lowered transfusion reliance, serving as a feasible individualized treatment strategy for this high-risk elderly AML cohort.