Low-Dose Decitabine versus Low-Dose Azacitidine in Lower-Risk MDS
Koji Sasaki, Elias Jabbour, Guillermo Montalban‐Bravo, Faezeh Darbaniyan, Kim‐Anh Do, Caleb A. Class, Nicholas J. Short, Rashmi Kanagal-Shamana, Tapan M. Kadia, Gautam Borthakur, Naveen Pemmaraju, Jörge E. Cortes, Farhad Ravandi, Yesid Alvarado, Kelly S. Chien, Rami S. Komrokji, Mikkael A. Sekeres, David P. Steensma, Amy E. DeZern, Gail J. Roboz, Kelly A. Soltysiak, Hui Yang, Hagop M. Kantarjian, Guillermo Garcia‐Manero
Abstract
BACKGROUND: The hypomethylating agents are part of the standard of care in the treatment of myelodysplastic syndromes (MDS), but their role in patients with lower-risk disease is unclear. METHODS: We randomly assigned patients with previously untreated MDS with low/intermediate-1 risk by the International Prognostic Scoring System with a Bayesian response-adaptive design to receive either 20 mg/m2 decitabine daily or 75 mg/m2 azacitidine daily on days 1 to 3 every 28-day cycle. RESULTS: A total of 113 patients were treated: 73 (65%) with decitabine and 40 (35%) with azacitidine. The overall response rate was 67% and 48% in the decitabine and azacitidine groups, respectively (P=0.042); among 59 patients with baseline transfusion dependency, 19 (32%) reached transfusion independence (decitabine, 16 of 39 [41%]; azacitidine, 3 of 20 [15%]; P=0.039). Of the 19 patients who reached transfusion independence, the median duration of transfusion independency was 22 months. Among 54 patients who were transfusion independent at baseline, 5 patients (9%) became transfusion dependent after therapy. No early death was observed. With a median follow-up of 68 months, the median overall event-free survival and overall survival were 17 months and 33 months, respectively. CONCLUSIONS: Attenuated dose treatment of hypomethylating agents in patients with lower-risk MDS can improve outcomes without dose-limiting side effects in a high-risk cohort as defined by the Lower-Risk Prognostic Scoring System. (Funded in part by The University of Texas MD Anderson Cancer Center and others; ClinicalTrials.gov number, NCT01720225.)