Patients with acute myeloid leukemia (AML) who received maintenance therapy with oral azacitidine had longer overall survival and relapse-free survival, according to research in The New England Journal of Medicine.

About 40% to 60% of patients with AML achieve complete remission with standard chemotherapy, but about 80% to 90% eventually relapse. Patients who have a longer first remission experience better survival outcomes. Maintenance therapy is not widely used among AML patients, in part because of the disease complexity and because of adverse events related to treatments.

A phase 3, randomized, double-blind, placebo-controlled trial compared oral azacitidine (CC-486) to placebo in patients with AML in first remission after intensive chemotherapy. Oral azacitidine is a hypomethylating agent, but with different pharmacokinetic and pharmacodynamic profiles than injectable azacitidine.

Continue Reading

The trial included patients older than age 55 years in complete remission, and who were not candidates for hematopoietic stem cell transplantation (HSCT); 472 patients were randomly assigned to receive either 300 mg of oral azacitidine (n=238) or placebo (n=234).

Overall survival for patients receiving oral azacitidine was significantly longer than those receiving placebo at follow-up (24.7 months vs 14.8 months, P <.001). The median follow-up time was 41.2 months. Patients receiving oral azacitidine had a median relapse-free survival of 10.2 months compared with 4.8 months in the placebo group (P <.001). Relapse-free survival at 1 year was also higher for patients receiving oral azacitidine (44.9% vs 27.4% with placebo).

Patients receiving oral azacitidine had similar quality of life scores to patients with placebo. The most common side effects were nausea, vomiting, and diarrhea, mostly during the first 2 cycles. These side effects were mostly controlled with medications and dose modifications, and these adverse events declined in subsequent cycles. Neutropenia, thrombocytopenia, and anemia were the most common hematologic adverse events in both groups, with adverse events occurring more frequently in the oral azacitidine group.

Overall, maintenance therapy with oral azacitidine prolonged survival and time to relapse, and did not worsen quality of life compared to placebo. Future studies should examine molecular characteristics to determine which patients may benefit most from maintenance therapy.

Disclosure: 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.


Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26):2526-2537. doi:10.1056/NEJMoa2004444