Efficacy and safety of venetoclax combination therapy for relapsed/refractory acute myeloid leukemia: a systematic review and meta-analysis

Background: Venetoclax combination therapy has emerged as a potential strategy for relapsed or refractory acute myeloid leukemia (AML). This study aims to expand the current knowledge base, guide future research, inform clinical decisions, and refine therapeutic strategies to improve outcomes for patients with this challenging hematologic malignancy.
Methods: A systematic search of PubMed, Embase, and Cochrane databases was conducted for English-language studies on venetoclax combination therapy in relapsed/refractory AML, spanning inception to November 2023. Duplicate publications, incomplete studies, animal experiments, literature reviews, and systematic reviews were excluded. Meta-analysis was performed using STATA 15.1.
Results: From 58 identified studies, seven met inclusion criteria for the meta-analysis. The pooled complete remission (CR) rate was 15.4%, and the composite complete remission (CRc) rate was 35.7%. Partial remission (PR) occurred in 2.6% of patients, while the non-remission (NR) rate was 24.4%. Among CRc patients, the minimal residual disease-negative ABBV-075 CRc (MRD-CRc) rate was 39.4%, and the morphologic leukemia-free state (MLFS) rate was 10.3%. Adverse events included febrile neutropenia (39.6%), thrombocytopenia (28.4%), hypokalemia (16.4%), fatigue (9.1%), diarrhea (10.0%), and nausea (4.3%). Subgroup analysis revealed varying efficacy across combinations: venetoclax with azacitidine demonstrated the highest CR (31.3%) and CRc (62.7%) rates, while venetoclax with idasanutlin showed moderate efficacy (CR: 6.1%, CRc: 26.5%), and venetoclax with mivebresib had the lowest CR (3.3%) and CRc (8.0%) rates.
Conclusion: Venetoclax combination therapies, particularly with azacitidine, show promise in improving treatment responses for relapsed/refractory AML patients. However, the high incidence of adverse events, notably febrile neutropenia and thrombocytopenia, underscores the need for careful safety assessment in clinical application.