The efficacy and adverse events of venetoclax in combination with hypomethylating agents treatment for patients with acute myeloid leukemia and myelodysplastic syndrome: a systematic review and meta-analysis

Hematology. 2020 Dec;25(1):414-423. doi: 10.1080/16078454.2020.1843752.


Objectives: To evaluate the efficacy and adverse effects of venetoclax(VEN) in combination with hypomethylating agents(HMAs) in acute myeloid leukemia(AML) or myelodysplastic syndrome(MDS).

Methods: Clinical studies were identified from the Cochrane Library, PubMed, Embase, Google Scholar, and Overall complete remission (CR) and overall response rate (ORR) were used to evaluate the efficacy of VEN in combination with HMAs for AML/MDS, the incidence of the 4 most common grade 3-4 adverse events was used to evaluate safety.

Results: We identified 13 studies that included a total of 1059 patients. 7 cohort studies and 5 non-randomized controlled trials(NRCTs) were analyzed by random-effects model, and subgroup analyses showed the pooled overall CR rate of 62% (95% CI 57-67%, I2 = 3%) for the new-diagnosed(ND) AML group, 39% (95% CI 30-48%, I2 = 28%) for relapsed/refractory(R/R)-AML, and 61% (95% CI 50-71%, I2 = 25%) for MDS, respectively. There was only one randomized controlled trial(RCT) that showed a CR rate of 66.4% in the patients who received azacitidine(AZA) plus VEN. A total of 8 studies reported adverse events, with cytopenia and infection being the most common grade 3-4 adverse events.

Conclusions: The addition of VEN to HMAs may provide significant clinical benefit for AML/MDS patients, where response rates are better in MDS and ND-AML than in R/R-AML, but attention should be paid to the possible increased risk of febrile neutropenia.

Keywords: Acute myeloid leukemia; hypomethylating agent; myelodysplastic syndrome; venetoclax.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Video-Audio Media

MeSH terms

  • Azacitidine* / adverse effects
  • Azacitidine* / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Models, Biological*
  • Myelodysplastic Syndromes / drug therapy*
  • Sulfonamides* / adverse effects
  • Sulfonamides* / therapeutic use


  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • Azacitidine
  • venetoclax