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

Autores de IIS La Fe

• Rebeca Rodríguez Veiga

  Autor

• Antonio Solana Altabella

  Autor

• Pau Montesinos Fernández

  Autor

Participantes ajenos a IIS La Fe

• Sanz-Solas A.
• Saiz-Rodríguez M.
• Simal S.C.
• Labrador J.

Grupos

• Grupo de Investigación de Farmacia

• Hematología y Hemoterapia

Abstract

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. © The Author(s) 2025.

Keywords

• Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Clinical Trials as Topic; Decitabine; Humans; Leukemia, Myeloid, Acute; Sulfonamides; Treatment Outcome; azacitidine; cytidine; decitabine; hypomethylating agent; unclassified drug; venetoclax; antineoplastic agent; azacitidine; decitabine; fused heterocyclic rings; sulfonamide; venetoclax; acute myeloid leukemia; adult; Article; cohort analysis; controlled study; cytogenetics; drug efficacy; ECOG Performance Status; human; major clinical study; meta analysis; minimal residual disease; monotherapy; neutropenia; neutrophil count; observational study; outcome assessment; overall survival; randomized controlled trial; thrombocytopenia; treatment duration; acute myeloid leukemia; clinical trial (topic); comparative study; drug therapy; mortality; treatment outcome