Wei et al (Chevassut).pdf (637.61 kB)
Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission
journal contribution
posted on 2023-06-09, 23:11 authored by Andrew H Wei, Hartmut Dohner, Christopher Pocock, Pau Montesinos, Boris Afanasyev, Hervé Dombret, Farhad Ravandi, Hamid Sayar, Jun-Ho Jang, Kimmo Porkka, Dominik Selleslag, Irwindeep Sandhu, Mehmet Turgut, Valentina Giai, Timothy ChevassutTimothy ChevassutBackground: Although induction chemotherapy results in remission in many older patients with acute myeloid leukemia (AML), relapse is common and overall survival is poor. Methods: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of the oral formulation of azacitidine (CC-486, a hypomethylating agent that is not bioequivalent to injectable azacitidine), as maintenance therapy in patients with AML who were in first remission after intensive chemotherapy. Patients who were 55 years of age or older, were in complete remission with or without complete blood count recovery, and were not candidates for hematopoietic stem-cell transplantation were randomly assigned to receive CC-486 (300 mg) or placebo once daily for 14 days per 28-day cycle. The primary end point was overall survival. Secondary end points included relapse-free survival and health-related quality of life. Results: A total of 472 patients underwent randomization; 238 were assigned to the CC-486 group and 234 were assigned to the placebo group. The median age was 68 years (range, 55 to 86). Median overall survival from the time of randomization was significantly longer with CC-486 than with placebo (24.7 months and 14.8 months, respectively; P<0.001). Median relapse-free survival was also significantly longer with CC-486 than with placebo (10.2 months and 4.8 months, respectively; P<0.001). Benefits of CC-486 with respect to overall and relapse-free survival were shown in most subgroups defined according to baseline characteristics. The most common adverse events in both groups were grade 1 or 2 gastrointestinal events. Common grade 3 or 4 adverse events were neutropenia (in 41% of patients in the CC-486 group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during CC-486 treatment. Conclusions: CC-486 maintenance therapy was associated with significantly longer overall and relapse-free survival than placebo among older patients with AML who were in remission after chemotherapy. Side effects were mainly gastrointestinal symptoms and neutropenia. Quality-of-life measures were maintained throughout treatment.
History
Publication status
- Published
File Version
- Published version
Journal
New England Journal of MedicineISSN
0028-4793Publisher
Massachusetts Medical SocietyExternal DOI
Volume
383Page range
2526-2537Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-03-02First Open Access (FOA) Date
2021-06-25First Compliant Deposit (FCD) Date
2021-03-01Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC