The prevention of relapse is the major therapeutic challenge in older patients with
acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive
chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or
myelodysplastic syndrome with
refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive
chemotherapy, we assessed the value of
azacitidine as postremission
therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 116 eligible patients were randomly (1:1) assigned to either observation (N = 60) or
azacitidine maintenance (N = 56; 50 mg/m2, subcutaneously, days 1-5, every 4 weeks) until relapse, for a maximum of 12 cycles. Fifty-five patients received at least 1 cycle of
azacitidine, 46 at least 4 cycles, and 35 at least 12 cycles. The maintenance treatment with
azacitidine was feasible. DFS was significantly better for the
azacitidine treatment group (logrank; P = .04), as well as after 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, 0.41-0.95; P = .026). The 12-month DFS was estimated at 64% for the
azacitidine group and 42% for the control group. OS did not differ between treatment groups, with and without censoring for allogeneic hematopoietic
cell transplantation. Rescue treatment was used more often in the observation group (n = 32) than in the
azacitidine maintenance group (n = 9). We conclude that
azacitidine maintenance after CR/CRi after intensive
chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).