A systematic review and meta - analysis of the efficacy and adverse events of azacitidine - plus - lenalidomide treatment for patients with acute myeloid leukemia, myelodysplastic syndromes and chronic myelomonocytic leukemia 1

Hematology. 2019 Dec;24(1):498-506. doi: 10.1080/16078454.2019.1631425.


Objectives: The addition of lenalidomide (LEN) to azacitidine (AZA) may further improve the outcomes of acute myeloid leukemia (AML) patients as well as patients with high-risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients although the evidence for this combination treatment is still relatively limited. This meta-analysis aimed to evaluate efficacy and adverse effects of AZA plus LEN for the treatment of patients with high-risk MDS, AML or CMML.

Methods: The current study systematically identified all cohort studies of patients with AML and/or MDS and/or CMML who received AZA in combination with LEN that reported the overall complete remission (CR) rate and/or overall response rate (ORR). A DerSimonian-d random-effects model with double arcsine transformation was used for the pooled rates and 95% confidence interval (CI) of the all outcomes.

Results: A total of 10 studies with 406 patients were identified and included into the meta-analysis. The pooled CR rate after the treatment with AZA-plus-LEN regimen was 33.0% (95% CI, 27.7%-38.7%, I2 = 18%) while the pooled ORR was 49.9% (95% CI, 38.4%-61.5%, I2 = 72%). Nonetheless, adverse events including grade 3-4 neutrophil toxicity events, platelet toxicity events and febrile neutropenia were common with AZA-plus-LEN regimen.

Conclusions: The current study may serve as a preliminary data to suggest that the addition of LEN may offer incremental benefit to patients with high-risk MDS, AML and CMML. However, randomized-controlled studies that directly compare the efficacy and adverse events of AZA-plus-LEN regimen versus AZA monotherapy are still needed.

Keywords: :Azacitidine; acute myeloid leukemia; chronic myelomonocytic leukemia; lenalidomide; myelodysplastic syndrome.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects
  • Cohort Studies
  • Female
  • Hematologic Diseases / chemically induced
  • Humans
  • Lenalidomide / administration & dosage
  • Lenalidomide / adverse effects
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myelomonocytic, Chronic / drug therapy*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Treatment Outcome


  • Lenalidomide
  • Azacitidine