Azacitidine maintenance after intensive chemotherapy improves DFS in older AML patients

Gerwin Huls, Dana A Chitu, Violaine Havelange, Mojca Jongen-Lavrencic, Arjan A van de Loosdrecht, Bart J Biemond, Harm Sinnige, Beata Hodossy, Carlos Graux, Rien van Marwijk Kooy, Okke de Weerdt, Dimitri Breems, Saskia Klein, Jürgen Kuball, Dries Deeren, Wim Terpstra, Marie-Christiane Vekemans, Gert J Ossenkoppele, Edo Vellenga, Bob Löwenberg

Research output: Contribution to journalArticleAcademicpeer-review


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/m 2, 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).

Original languageEnglish
Pages (from-to)1457-1464
Number of pages8
Issue number13
Early online date10 Jan 2019
Publication statusPublished - 28 Mar 2019


  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic/therapeutic use
  • Azacitidine/therapeutic use
  • Disease-Free Survival
  • Female
  • Humans
  • Leukemia, Myeloid, Acute/drug therapy
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Remission Induction


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