Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients
Mené sur 116 patients âgés de plus de 60 ans et atteints d'une leucémie aiguë myéloïde, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans maladie, d'un traitement d'entretien par azacitidine, après une chimiothérapie intensive
Azacitidine maintenance is feasible in intensively treated older patients with newly diagnosed AML.Azacitidine maintenance, with adjustment for poor risk cytogenetic risk and platelet count at diagnosis, improves DFS. 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 III study (HOVON97) in older patients (≥ 60 years) with AML or MDS-RAEB, in CR/CRi after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as post remission therapy with respect to the disease free survival (DFS; primary endpoint) and overall survival (OS; secondary endpoint). In total 116 eligible patients were randomly (1:1) assigned to either observation (N=60) or azacitidine maintenance (N=56; 50 mg/m2, s.c., day 1-5, q 4 weeks) until relapse for a maximum of 12 cycles: 55 patients received at least 1 cycle of azacitidine, 46 at least 4 cycles and 35 patients at least 12 cycles. The maintenance treatment with azacitidine was feasible. DFS was significantly better for the azacitidine treatment group (logrank; P=0.04), also following adjustment for poor-risk cytogenetic abnormalities at diagnosis and platelet count at randomization (as surrogate for CR vs CRi; Cox regression; HR = 0.62; 95% CI 0.41-0.95; P=0.026). The 12 months DFS was estimated at 64% for the azacitidine group and at 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 arm (n=32) than in the azacitidine maintenance arm (n=9). We conclude that azacitidine maintenance after CR following intensive chemotherapy is feasible and significantly improves DFS. The study is registered with The Netherlands Trial Registry (NTR1810) and EudraCT (2008-001290-15).