Dose‐Adjusted Treatment With 7‐Day Venetoclax Plus Azacitidine or Decitabine in Patients With Acute Myeloid Leukaemia

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Abstract
Acute myeloid leukaemia (AML) in older or unfit patients is commonly treated with hypomethylating agents (HMA) plus venetoclax (VEN), but prolonged VEN exposure often causes substantial haematological toxicity. We retrospectively analysed 61 elderly AML patients treated with HMA + VEN for 7 (7d), 14 (14d) or > 14 days (> 14d) per cycle. Best overall response rate was 76% and did not differ significantly between schedules ( p = 0.38). Median overall survival (OS) was numerically longer with 7d (28.4 months) than with 14d (11.4 months) or > 14d (6.7 months), although unadjusted differences were not significant ( p = 0.23). At cycle level, the 7d schedule was associated with fewer infections and more complication‐free cycles than both longer schedules, while bleeding events were similar. Grade 4 cytopenias and platelet transfusion requirements were also lower with 7d. In an adjusted Cox model, prior HMA exposure, non‐favourable ELN 2024 risk and age ≥ 75 years were associated with inferior OS, whereas the 7d schedule remained associated with improved OS versus > 14d (HR 0.33, p = 0.03). Higher recent grade 4 neutropenia burden was independently associated with inferior OS. These findings suggest that abbreviated VEN exposure may improve tolerability without clear loss of efficacy in AML patients ineligible for intensive chemotherapy.

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