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Low-Dose Decitabine versus Low-Dose Azacitidine in Lower-Risk MDS

  • Koji Sasaki, M.D., Ph.D.1,
  • Elias Jabbour, M.D.1,
  • Guillermo Montalban-Bravo, M.D.1,
  • Faezeh Darbaniyan, Ph.D.2,
  • Kim-Anh Do, Ph.D.2,
  • Caleb Class, Ph.D.2,
  • Nicholas J. Short, M.D.1,
  • Rashmi Kanagal-Shamana, M.D.3,
  • Tapan Kadia, M.D.1,
  • Gautam Borthakur, M.D.1,
  • Naveen Pemmaraju, M.D.1,
  • Jorge Cortes, M.D.4,
  • Farhad Ravandi, M.D.1,
  • Yesid Alvarado, M.D.1,
  • Kelly Chien, M.D.1,
  • Rami Komrokji, M.D.5,
  • Mikkael A. Sekeres, M.D.6,
  • David P. Steensma, M.D.7,
  • Amy DeZern, M.D., M.H.S.8,
  • Gail Roboz, M.D.9,
  • Kelly Soltysiak, Ph.D.1,
  • Hui Yang, M.D. Ph.D.1,
  • Hagop M. Kantarjian, M.D.1, and
  • Guillermo Garcia-Manero, M.D.1
Published August 9, 2022
NEJM Evid 2022; 1 (10)
DOI:https://doi.org/10.1056/EVIDoa2200034
Issue

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.)


Supported in part by The University of Texas MD Anderson Cancer Center support grant CA016672, The University of Texas MD Anderson Cancer Center MDS/AML Moon Shot, and Leukemia Texas. Dr. Do was partially supported by National Cancer Institute Cancer Center support grant P30 CA016672, National Institutes of Health grants UL1TR003167 and 5R01GM122775, the prostate cancer Specialized Program of Research Excellence (SPORE) P50 CA140388, Cancer Prevention & Research Institute of Texas grant RP160693, and the Moon Shots funding at The University of Texas MD Anderson Cancer Center. This is a study from the U.S. MDS Clinical Research Consortium and received funding from the Edward P. Evans Foundation.

Disclosure forms provided by the authors are available with the full text of this article.

A data sharing statement provided by the authors is available with the full text of this article.

Dr. Garcia-Manero can be contacted at [email protected] or at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 428, Houston, TX 77030.

Figures/Media

  • Figure 1. Survival by Therapy Event-Free Survival (Panel A) and Overall Survival (Panel B).
    Figure 1

    AZA denotes azacitidine; DEC, decitabine; EFS, event-free survival; and OS, overall survival.

  • Figure 2. Survival by the Lower-Risk Prognostic Scoring System.
    Figure 2

    AZA denotes azacitidine; DEC, decitabine; and OS, overall survival.

  • Table 1. Patient Characteristics.
  • Table 2. Response.
  • Table 3. Response by the Status of Transfusion Dependency at Baseline.