ASH 2025: Shorter azacitidine regimen safely improves outcomes in lower-risk MDS patients
MD Anderson Research News December 07, 2025
Azacitidine is a type of targeted therapy known as a hypomethylating agent, commonly used in treating myelodysplastic syndromes (MDS)
Five-day azacitidine showed superior survival outcomes and disease control in lower-risk MDS patients
All trial regimens evaluated were safe, but the five-day regimen offered the best balance of safety and efficacy
ORLANDO, DECEMBER 7, 2025 – Patients with lower-risk myelodysplastic syndromes (MDS) experienced strong responses with fewer side effects when treated with a five-day azacitidine compared to shorter durations of azacitidine or decitabine, according to researchers at The University of Texas MD Anderson Cancer Center.
Final data from the trial were presented today by Ian Bouligny, M.D., assistant professor of Leukemia, at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 487). All ASH content from MD Anderson can be found at MDAnderson.org/ASH.
“For patients with lower-risk MDS, a five-day duration of azacitidine was safe and effective, showing improved event-free survival and overall survival compared to three-day durations of azacitidine or decitabine,” Bouligny said. “We’ve seen firsthand how this approach improves outcomes and enhances the overall treatment experience for our patients in clinic.”
Why did researchers study shorter durations of azacitidine for treating MDS?
Traditionally, hypomethylating agents, such as azacitidine and decitabine, are used in longer regimens – seven days for azacitidine and five days for decitabine – for treating patients with higher-risk MDS. These treatments, though, can cause unwanted side effects, such as excessive myelosuppression. Therefore, researchers wanted to investigate if shorter durations offered the same benefits with less toxicity for those with lower-risk MDS.
What did researchers discover about shorter duration treatment using azacitidine?
Researchers compared three regimens in this study – three days of decitabine, three days of azacitidine, and five days of azacitidine – to determine which had the best outcomes. The trial enrolled a total of 247 patients across multiple centers into two groups, transfusion-dependent (151) and transfusion-independent (96) groups. Transfusion dependence was defined as requiring a red blood cell or platelet transfusion at any point before treatment.
The five-day regimen offered the best balance of safety and efficacy. This course demonstrated better event-free survival (EFS), the study’s primary endpoint, in transfusion-dependent patients over three-day azacitidine, and improved overall survival (OS) over both alternatives. After controlling baseline characteristics, the five-day regimen was associated with consistently better EFS and OS than the other courses.
The overall response rate was 48% and 70% for transfusion-dependent patients and transfusion independent patients, respectively, when treated with the five-day regimen. In addition, many patients were able to avoid blood or platelet transfusions after treatment without excess toxicity.
How can this study change the way low-risk MDS is treated?
The findings suggest that a shorter course of hypomethylating agents is a viable option for patients with lower-risk MDS, with the five-day azacitidine regimen being the most effective treatment. These results are important because many clinical trials for lower-risk MDS have used transfusion independence as the primary endpoint.
This study investigated how these drugs change the natural history of the disease by using EFS as the primary endpoint. The investigators showed that five-day azacitidine significantly improves survival and alters the natural course of lower-risk MDS. Investigators did not observe any increased toxicity with five-day compared to three-day azacitidine or three-day decitabine. Researchers are currently investigating an oral formulation of azacitidine-cedazuridine.
“We are excited to identify the optimal azacitidine dosing schedule in lower-risk MDS,” Bouligny added. “We 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.”
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The study was supported by funding from the Edward P. Evans Foundation, the National Institutes of Health/National Cancer Institute CCA016672), and MD Anderson institutional funding. A full list of collaborating authors and their disclosures can be found with the abstract.