Maintenance therapy with azacitidine after intensive chemotherapy resulting in complete remission (CR) in older patients with newly diagnosed acute myeloid leukemia (AML) was feasible and significantly improved disease-free survival (DFS), according to research published in Blood.
Approximately three-quarters of patients with AML are 60 years or older, with CR rates after intensive chemotherapy between 40% and 55% and a median DFS of 6 to 12 months. Preventing relapse is a major treatment challenge in patients with AML who achieve CR following intensive chemotherapy.
In a randomized phase 3 trial (HOVON-97), the Dutch-Belgian Hemato-Oncology Cooperative Group studied patients at least 60 years old with newly diagnosed AML or myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB). Patients achieved CR or CR with incomplete hematologic recovery (CRi) after at least 2 rounds of intensive chemotherapy.
Of the 116 patients eligible for the trial, 60 were randomly assigned to observation and 56 were randomly assigned to maintenance azacitidine until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of azacitidine, 46 received at least 4 cycles, and 35 received the maximum of 12 cycles. The high adherence to treatment supported maintenance azacitidine as a feasible therapeutic approach.
DFS was significantly better in the azacitidine arm (logrank; P =.04), even with adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; hazard ratio = 0.62; 95% confidence interval [CI], 0.41-0.95; P =.026).
The estimated 12-month DFS was 64% for the azacitidine arm and 42% for the observational arm. OS was similar between treatment arms, both with and without censoring for allogeneic hematopoietic stem cell transplantation.
Rescue therapy was used more frequently in the observational arm (32 patients) compared with the azacitidine arm (9 patients).
Data from this study supported the feasibility and effectiveness of azacitidine maintenance in newly diagnosed older patients with AML receiving intensive treatment, the authors concluded. Furthermore, this therapeutic approach was found to significantly improve DFS.
1. Huls G, Chitu DA, Havelange V, et al. Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients [published online January 10, 2019]. Blood. doi: 10.1182/blood-2018-10-879866