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A randomized phase II study of low-dose decitabine versus low-dose azacitidine in lower risk MDS and MDS/MPN

Elias Jabbour, Nicholas J. Short, Guillermo Montalban-Bravo, Xuelin Huang, Carlos Bueso-Ramos, Wei Qiao, Hui Yang, Chong Zhao, Tapan Kadia, Gautam Borthakur, Naveen Pemmaraju, Koji Sasaki, Zeev Estrov, Jorge Cortes, Farhad Ravandi, Yesid Alvarado, Rami Komrokji, Mikkael A. Sekeres, David P. Steensma, Amy DeZern, Gail Roboz, Hagop Kantarjian and Guillermo Garcia-Manero

Key points

  • Low-dose hypomethylating agents are safe and effective in patients with lower-risk MDS and MDS/MPN.

  • Decitabine was associated higher response rates compared to azacitidine, especially in patients with higher-risk features.

Abstract

Background: Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine versus low-dose azacitidine in this group of patients. Methods: Adults with low- or intermediate-1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, by the International Prognostic Scoring System were randomized using a Bayesian adaptive design to receive either azacitidine 75 mg/m2 IV/SC daily or decitabine 20 mg/m2 IV daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Results: Between 11/2012 and 2/2016, 113 patients were treated, 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate-1-risk. The median number of cycles received was 9. The overall response rate was 70% and 49% (p=0.03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine (p=0.2). Cytogenetic response rates were 61% and 25% (p=0.02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months -- 20 and 13 months for patients treated with decitabine and azacitidine, respectively (p=0.1). Treatment was well tolerated with a 6-week mortality rate of 0%. Conclusions: The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their impact on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225).

  • Submitted June 1, 2017.
  • Accepted July 24, 2017.