Comparative efficacy of venetoclax and hypomethylating agents in acute myeloid leukemia treatment: a meta-analysis of clinical trials and Real-World outcomes

This meta-analysis, comprising 24 studies, evaluated the efficacy of venetoclax (VEN) in combination with hypomethylating agents (HMAs), including azacitidine (AZA) and decitabine (DEC), in untreated patients with acute myeloid leukemia (AML), comparing outcomes from clinical trials and real-world practice. No significant difference in composite complete response (CRc) rates was observed between clinical trials (52%, 95% CI: 39-65%) and real-world studies (67%, 95% CI: 47-87%). However, overall survival (OS) was significantly longer in clinical trials (13.98 months, 95% CI: 11.89-16.07) compared to real-world cohorts (9.35 months, 95% CI: 8.46-10.23; p < 0.005). In real-world studies, the VEN + HMA combination was associated with a significantly higher CRc rate (67%, 95% CI: 48-85%) compared to HMA monotherapy (17%, 95% CI: 13-21%; p < 0.005), although no significant difference in OS was observed between these groups (9.35 vs. 9.38 months; p = 0.964). These findings highlight the need to optimize the implementation of VEN + HMA regimens in clinical practice, as real-world outcomes remain inferior to those reported in clinical trials.