TY - JOUR
T1 - Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN
AU - Jabbour, Elias
AU - Short, Nicholas J.
AU - Montalban-Bravo, Guillermo
AU - Huang, Xuelin
AU - Bueso-Ramos, Carlos
AU - Qiao, Wei
AU - Yang, Hui
AU - Zhao, Chong
AU - Kadia, Tapan
AU - Borthakur, Gautam
AU - Pemmaraju, Naveen
AU - Sasaki, Koji
AU - Estrov, Zeev
AU - Cortes, Jorge
AU - Ravandi, Farhad
AU - Alvarado, Yesid
AU - Komrokji, Rami
AU - Sekeres, Mikkael A.
AU - Steensma, David P.
AU - DeZern, Amy
AU - Roboz, Gail
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
N1 - Funding Information:
This work is supported in part by the University of Texas MD Anderson Cancer Center Support Grant CA016672, the University of Texas MD Anderson MDS/AML Moon Shot, and the MDS Clinical Research Consortium, which is funded by the Edward P. Evans Foundation.
Publisher Copyright:
© 2017 by The American Society of Hematology.
PY - 2017/9/28
Y1 - 2017/9/28
N2 - 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).
AB - 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).
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U2 - 10.1182/blood-2017-06-788497
DO - 10.1182/blood-2017-06-788497
M3 - Article
C2 - 28774880
AN - SCOPUS:85030033047
SN - 0006-4971
VL - 130
SP - 1514
EP - 1522
JO - Blood
JF - Blood
IS - 13
ER -