Long-Term COMMANDS Data Reinforce Luspatercept as Frontline MDS Therapy

After a Frontline Forum program, Amer Zeidan, MBBS, MD, and Raji Shameem, MD, discussed how long-term data from the phase 3 COMMANDS trial (NCT03682536) are shaping frontline treatment goals in lower-risk myelodysplastic syndromes (MDS).¹ COMMANDS compared luspatercept-aamt (Reblozyl) with epoetin alfa in patients with erythropoiesis-stimulating agent-naive, transfusion-dependent disease.

With extended follow-up showing markedly longer transfusion independence with luspatercept, both physicians described how the data have raised expectations for frontline therapy, including a growing population of long-term responders who remain transfusion free for 2.5 years or longer.

Zeidan is a professor of medicine at Yale School of Medicine and chief of the Division of Hematologic Malignancies, director of Hematology Early Therapeutics Research, and assistant director of the Clinical Trial Office for Hematology at Yale Comprehensive Cancer Center. Shameem is a hematologist and medical oncologist at the Orlando Health Cancer Institute.

Transcript:

CancerNetwork: The 3-year COMMANDS data showed that luspatercept nearly doubled the duration of transfusion independence compared with epoetin alfa. How do these long-term data shift your foundational treatment goals for lower-risk patients?

Shameem: COMMANDS changed the treatment landscape for our [patients with] lower-risk MDS. It enrolled patients who were both ring sideroblast [RS] positive and RS negative, and the long-term follow-up data on durability are quite remarkable. It has raised the bar for what we expect from frontline therapy in low-risk MDS. Seeing patients achieve a year and a half or longer without a transfusion is remarkable, and I feel that’s the goal. The best transfusion is no transfusion, and that matches what I see in my practice. I have many patients who haven’t seen a transfusion, and I tend to start before a patient needs one, in line with the FDA approval.² It’s been a nice addition to my practice and, as I said, it has raised the bar.

Zeidan: I would add that this is another piece of data generated since the initial COMMANDS disclosure, and with each additional piece of data, the role of luspatercept in frontline treatment is being cemented. We saw trends toward improved survival, we see higher response rates in most patients, and we see longer duration of response and higher rates of what I call “super-responders,” the patients with the longest transfusion independence of 2.5 years or more. The data are coming together nicely on the durability and clinical benefit of luspatercept as a frontline treatment.

References

1. Della Porta MG, Garcia-Manero G, Santini V, et al. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024;11(9):e646-e658. doi:10.1016/S2352-3026(24)00203-5
2. U.S. FDA approves Bristol Myers Squibb’s Reblozyl® (luspatercept-aamt) as first-line treatment of anemia in adults with lower-risk myelodysplastic syndromes (MDS) who may require transfusions. News release. Bristol Myers Squibb. August 28, 2023. Accessed June 30, 2026. https://bit.ly/3qH7YEQ