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

Abstract

This meta-analysis, comprising 24 studies, evaluated the efficacy of venetoclax (VEN) in combination with hypomethylat-ing 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.