This article is part of the December 2022 Editor’s Pick acute myeloid leukemia, which consists of a selection of clinically relevant literature on AML from the last two years. This selection was made by the NTVH literature committee.
View the entire selection here.
A new phase III study by Wei et al. looked at the impact of azacitidine maintenance treatment when initiated in the first remission period of an elderly AML patient. Here azacitidine (CC-486) have a positive impact on both relapse-free and overall survival.
Although induction chemotherapy leads to remission in many older patients with AML, relapses are common and the overall survival prognosis is poor in these patients. A new randomised, double-blind, placebo-controlled phase III study investigated the use of oral azacitidine (the hypomethylating agent CC-486 with aberrant biological activity of injected azacitidine) as maintenance therapy in AML patients in first remission after intensive chemotherapy . To be included in the study, patients had to be older than 55, be in complete remission with or without full recovery of blood counts, and not be eligible for hematopoietic stem cell transplantation. Participants received either 300 mg of CC-486 once daily or placebo for 14 days, in 28-day cycles. The primary endpoint was overall survival and secondary endpoints were relapse-free survival and health-related quality of life.
Results
A total of 472 patients underwent randomization of which 238 were assigned to the CC-486 arm and 234 to the placebo arm. The median age of the participants was 68 years (range: 55-86). Treatment with CC-486 resulted in a median overall survival of 24.7 months versus 14.8 months with placebo (p<0.001). Median relapse-free survival was also significantly extended to 10.2 months with CC-486 compared to 4.8 months with placebo (p<0.001). These clinical benefits of CC-486 were observed in the majority of subgroups studied.
The most common adverse reactions in both groups consisted of Grade 1 or 2 gastrointestinal events. Common Grade 3 or 4 adverse reactions were neutropenia (41% in CC-468 versus 24% in placebo) and thrombocytopenia (22% in CC-468 versus 21% on placebo). Health-related quality of life was maintained during CC-468 treatment.
Conclusion
With this, the researchers conclude that maintenance treatment with CC-486 in elderly AML patients, who are in remission after chemotherapy, is associated with a significantly longer relapse-free and overall survival compared to placebo. The side effects of this treatment mainly consisted of gastrointestinal symptoms and neutropenia. Quality of life did not appear to be significantly affected by treatment.
Reference
Wei AH, Döhner H, Pocock C, et al. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. New England Journal of Medicine 2020;383:2526-37.