Luspatercept Improves Reliance on Blood Transfusions for Patients With Lower-Risk MDS

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Patients with lower-risk myelodysplastic syndromes (MDS) who received luspatercept to treat anemia instead of erythropoiesis-stimulating agents (ESAs)—the current standard of care—needed fewer blood transfusions and clinic visits. These findings from the phase III COMMANDS trial were presented by Guillermo Garcia-Manero, MD, at the 2023 ASCO Annual Meeting (Abstract 7003).

About the COMMANDS Trial

Luspatercept is an erythroid maturation agent that helps the bone marrow grow erythroid cells into functional, mature red blood cells. The global phase III COMMANDS clinical trial included 354 people who had lower-risk MDS and required red blood cell transfusions to treat anemia. The participants in this study had not previously received treatment with an ESA. The open-label, randomized phase III trial included participants from more than 20 countries. The median age of the participants was 74 years, and most were White (80%) and men (56%). All participants had lower-risk MDS as classified by the revised International Prognostic Scoring System (IPSS-R). None had received previous treatment with an ESA and needed to receive transfusions of red blood cells.

Guillermo Garcia-Manero, MD

Guillermo Garcia-Manero, MD

The participants were divided into two groups: 178 received luspatercept by injection once every 3 weeks for at least 24 weeks, and 176 received the ESA epoetin alfa by injection once a week for at least 24 weeks. After median treatment durations of 41.6 weeks for luspatercept and 27 weeks for epoetin alfa, there were 301 participants included in the planned interim data analysis.

Key Findings

The primary endpoint of this study was transfusion independence for at least 12 weeks with a concurrent mean hemoglobin increase ≥ 1.5 g/dL within the first 24 weeks of treatment. At the time of this planned interim data analysis, 58.5% of patients receiving luspatercept achieved this endpoint, compared with 31.2% of those receiving epoetin alfa.

The secondary endpoints in the study included hematologic improvement-erythroid (HI-E) response ≥ 8 weeks and transfusion independence at 24 weeks and ≥ 12 weeks. Across these endpoints, luspatercept was more effective than epoetin alfa: 74.1% vs 51.3% for HI-E response, respectively; 47.6% vs 29.2% for 24-week transfusion independence; and 66.7% vs 46.1% for ≥ 12-week transfusion independence. 

“In this study, people who received luspatercept were significantly more likely to experience freedom from transfusions of red blood cells than those who received epoetin alfa. This is important, as ESAs have been the first-line treatment for patients with lower-risk MDS for decades,” said lead author Dr. Garcia-Manero, Professor in the Department of Leukemia and Chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center. “Luspatercept could potentially alter this treatment landscape such that patients could receive luspatercept first instead of ESAs. Patients will need to visit the clinic less often and receive blood transfusions less frequently. They will benefit from improved quality of life and better outcomes.”

Treatment-emergent adverse events were slightly more common among those who received luspatercept (n = 164, 92.1%) than those who received epoetin alfa (n = 150, 85.2%). A total of eight patients (4.5%) in the luspatercept group and four patients (2.3%) in the epoetin alfa group stopped treatment. More participants receiving luspatercept reported treatment-related adverse events than those receiving epoetin alfa (30.3% vs 17.6%, respectively). The most common adverse events suspected to be related to treatment with luspatercept were nausea (5.1%), fatigue (3.9%), dyspnea (3.4%), and hypertension (3.4%). There were four (2.2%) participants receiving luspatercept and five (2.8%) participants receiving epoetin alfa whose disease progressed to acute myeloid leukemia. Overall death rates were comparable between both treatment groups (18% in the luspatercept group vs 18.2% in the epoetin alfa group).

In 2020, luspatercept received approval from the U.S. Food and Drug Administration for the treatment of anemia among those with lower-risk MDS after ESAs had stopped working or for those who cannot receive ESAs.

Next Steps

These results are from a scheduled data analysis done before the completion of the study. It represents findings from approximately 80% of the study participants. The next steps will be to evaluate the data from all patients who completed 24 weeks of treatment. In addition, all participants will be observed for up to 5 years to monitor how they are doing.

ASCO Perspective

“In patients with anemia with lower-risk MDS who depend on red blood cell transfusions, luspatercept almost doubles the number of people who achieve independence from transfusions for a period lasting 12 weeks or more, when compared with epoetin alfa, a current standard-of-care treatment. Luspatercept may be an effective first treatment option for anemia associated with lower-risk MDS,” said ASCO expert Olatoyosi Odenike, MD, FASCO.

Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.