A multicenter trial led by investigators at The University of Texas MD Anderson Cancer Center demonstrated that a 5-day regimen of azacitidine provides the best balance of efficacy and safety for patients with lower-risk myelodysplastic syndromes (MDS). The researchers compared three abbreviated hypomethylating agent schedules—3 days of azacitidine, 3 days of decitabine, and 5 days of azacitidine—and found that the 5-day regimen resulted in improved event-free and overall survival without increasing toxicity. Final results were presented by Ian Bouligny, MD, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 487).
Study Details
A total of 247 patients were enrolled in the trial, divided into transfusion-dependent (n = 151) and transfusion-independent (n = 96) cohorts. Transfusion dependence was defined as a need for red blood cell or platelet transfusion before treatment. The median age was 70.8 years (range = 24–88 years), and 25% were female.
Across both cohorts, the 5-day azacitidine regimen produced consistently superior outcomes. In transfusion-dependent patients, event-free survival—the study’s primary endpoint—was significantly better with the 5-day schedule than with 3-day azacitidine. Overall survival was also improved when compared with either 3-day regimen. After adjustment for baseline characteristics, the 5-day regimen remained associated with favorable outcomes across endpoints.
According to Dr. Bouligny, “For patients with lower-risk MDS, a 5-day duration of azacitidine was safe and effective, showing improved event-free survival and overall survival compared to 3-day durations of azacitidine or decitabine.” He added that the regimen “improves outcomes and enhances the overall treatment experience” for patients managing chronic therapy.
Standard hypomethylating agent therapy for higher-risk MDS traditionally involves longer treatment courses—7 days for azacitidine and 5 days for decitabine—but these schedules may cause excessive myelosuppression. To determine whether shorter regimens could reduce toxicity while maintaining benefit in lower-risk disease, investigators evaluated the three approaches. The 5-day azacitidine regimen achieved overall response rates of 48% in transfusion-dependent patients and 70% in transfusion-independent patients, with many participants able to avoid subsequent blood or platelet transfusions. In addition, no increase in toxicity was observed compared with the shorter, 3-day regimens.
These findings highlight the value of using event-free survival rather than transfusion independence alone to understand how therapy alters the natural history of lower-risk MDS. The results indicate that a 5-day hypomethylating course not only improves survival but may have a meaningful influence on long-term disease trajectory.
Future Directions
Investigators are now studying oral formulations of azacitidine plus cedazuridine, which may offer even more convenience while maintaining efficacy. “We are excited to identify the optimal azacitidine dosing schedule in lower-risk MDS,” noted Dr. Bouligny, adding that researchers are “eager to see how these results translate to improved outcomes with a convenient oral formulation for our patients with lower-risk MDS in the near future.”
Disclosure: The study was supported by the Edward P. Evans Foundation, the National Institutes of Health/National Cancer Institute, and MD Anderson. For full disclosures of all study authors, visit hematology.org.
