Randomized phase 2 study of low-dose decitabine vs 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 DeZernGail Roboz, Hagop Kantarjian, Guillermo Garcia-Manero

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

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 vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m2 intravenously/subcutaneously daily or decitabine 20 mg/m2 intravenously daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between November 2012 and February 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 patients. The median number of cycles received was 9. The ORRs were 70% and 49% (P 5 .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 5 .2). Cytogenetic response rates were 61% and 25% (P 5 .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 5 .1). Treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225).

Original languageEnglish (US)
Pages (from-to)1514-1522
Number of pages9
JournalBlood
Volume130
Issue number13
DOIs
StatePublished - Sep 28 2017

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Jabbour, E., Short, N. J., Montalban-Bravo, G., Huang, X., Bueso-Ramos, C., Qiao, W., Yang, H., Zhao, C., Kadia, T., Borthakur, G., Pemmaraju, N., Sasaki, K., Estrov, Z., Cortes, J., Ravandi, F., Alvarado, Y., Komrokji, R., Sekeres, M. A., Steensma, D. P., ... Garcia-Manero, G. (2017). Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood, 130(13), 1514-1522. https://doi.org/10.1182/blood-2017-06-788497