The efficacy and safety of venetoclax and azacytidine combination treatment in patients with acute myeloid leukemia and myelodysplastic syndrome: systematic review and meta-analysis

Hematology. 2023 Dec;28(1):2198098. doi: 10.1080/16078454.2023.2198098.

Abstract

Objectives: The meta-analysis sought to evaluate the efficacy and safety of a combination of venetoclax (Ven) and azacitidine (AZA) in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Methods: We searched PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, and Web of Science for eligible studies from inception to June 2022. We used the Cochrane Risk of Bias 2.0 (RoB 2.0) and Methodological Index for Non-Randomized Studies (MINORS) to evaluate the quality of the included literature. The inverse variance method was used to calculate the pooled proportion and 95% confidence interval (CI).

Results: The meta-analysis included nineteen studies with a total of 1615 patients. The pooled overall CR/CRi (complete response (CR)/complete response with incomplete blood count recovery (CRi)) rate for AML and MDS was 57.9% (95% CI 49.5-65.9%, I2 = 83%). Subgroup analyses showed that the rate of pooled CR/CRi was 67.5% (95% CI 61.1-73.3%, I2 = 54%) for the new-diagnosed (ND) AML group, 30% (95% CI 20-44.1%, I2 = 66%) for relapsed/refractory (R/R) AML, and 67.6% (95% CI 52.6-79.8%, I2 = 65%) for MDS, respectively. One randomized controlled trial (RCT) showed that CR/CRi was 64.7% in ND-AML patients. A total of 9 studies reported adverse events, with neutropenia being the most common of grade 3-4 adverse events, with a rate of 53.7% (95% CI 61.1-73.3%, I2 = 54%).

Conclusion: The present meta-analysis demonstrated that the Ven + AZA regimen is efficacious for the treatment of AML and MDS, with it being more effective for ND-AML than R/R AML. The most common adverse effects of this regimen are grade 3-4 neutropenia and neutropenia with fever.

Keywords: Meta-analysis; acute myeloid leukemia; azacitidine; myelodysplastic syndrome; venetoclax.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Azacitidine / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / etiology
  • Myelodysplastic Syndromes* / drug therapy
  • Myelodysplastic Syndromes* / etiology
  • Neutropenia* / etiology

Substances

  • Azacitidine
  • venetoclax