Results from a phase 3 study evaluating the use of azacitidine in patients with high-risk acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) showed no benefit in relapse-free survival (RFS) with this treatment approach after completion of allogeneic hematopoietic stem cell transplantation. Study results were published in the journal Blood Advances.

In this open-label study ( Identifier: NCT00887068), patients with high-risk AML/MDS were randomly assigned to either azacitidine treatment (93 patients) or observation (94 patients) following transplantation. Azacitidine was administered subcutaneously at a dosage of 32 mg/m2 per day for 5 days, every 4 weeks for 12 cycles. The primary study endpoint was RFS.

The total number of patients treated in the azaciditine arm was 87, and they were given a median of 4 cycles of therapy. For surviving patients, the median study follow-up was 4.6 years with azaciditine and 4.06 years with observation.

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The median RFS was 2.07 years with azaciditine, compared with 1.28 for the observation group (P =.19). In a multivariate analysis, the hazard ratio (HR) for risk of relapse was 0.86 (95% CI, 0.59-1.3; P =.43), indicating no RFS benefit with azacitidine as a maintenance therapy compared with observation.

Overall survival (OS) also showed no significant difference between arms, with the median OS being 2.52 for the azaciditine group and 3.56 years for the observation group (P =.43). In a multivariate analysis, the HR for OS improvement was 0.84 (95% CI, 0.55-1.29; P =.43), indicating no OS improvement with the treatment.

Incidence of acute graft-vs-host disease (GVHD), from grades 2 to 4 and 3 to 4, did not significantly differ between arms. The day-100 cumulative incidence of acute GVHD of grades 2 to 4 for the azacitidine group was 25.5%, and for the observation group it was 28.7% (P =.73). For acute GVHD of grades 3 to 4 and chronic GVHD, the rates were also not significantly different between arms.

Rates of adverse events (AEs) were 87.4% for at least 1 AE among patients treated with azacitidine and 72.3% for at least 1 AE among patients in the observation group. Mean total toxicity burden was calculated to be 7.3 for patients receiving azacitidine and 4.8 for the observation arm. One patient in the azacitidine arm had a grade 5 AE associated with aspiration pneumonia.

The study investigators reported that treatment with azacitidine was safe and feasible, although the study failed to find a benefit with maintenance azacitidine in this population. However, the investigators noted that the dosing regimen of azacitidine used in this study may have been insufficient for showing an improvement in outcomes.

“This finding indicates the importance of effectively conducting randomized trials of posttransplant maintenance strategies to establish therapeutic benefit,” the study investigators concluded.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Oran B, de Lima M, Garcia-Manero G, et al. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients. Blood Adv. 2020;4(21):5580-5588. doi:10.1182/bloodadvances.2020002544