Clinical outcomes with azole and other CYP3A4 inhibitor coadministration during venetoclax plus azacitidine or decitabine therapy in newly diagnosed acute myeloid leukemia: a systematic review and meta-analysis

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Venetoclax plus azacitidine or decitabine (VEN-HMA) is a frontline option for newly diagnosed acute myeloid leukemia (AML). Venetoclax is metabolized by CYP3A4 and in practice is frequently coadministered with CYP3A4 inhibitors, yet whether this affects outcomes is unknown. We systematically searched four databases (PROSPERO CRD420251152772) for newly diagnosed AML treated with VEN-HMA reporting composite complete remission (CRc), invasive fungal infection or survival by CYP3A4-inhibitor status, through August 2026. Nineteen studies (2021–2026) were included, twelve contributing to the quantitative syntheses. Across five comparative cohorts, the pooled odds ratio for CRc was 0.81 (95% CI 0.58–1.13; I2=0%); among six single-arm cohorts, the pooled CRc proportion was 67.1% (62.0–71.9%), matching no-inhibitor and trial benchmarks (∼66–67%). Fungal infection was pooled but uninformative; survival was not pooled. Overall certainty was very low. Concomitant CYP3A4-inhibitor exposure was not associated with compromised remission, consistent with the feasibility of reduced-dose regimens pending prospective confirmation.