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 α, a current standard of care treatment. Luspatercept may be an effective first treatment option for anemia associated with lower-risk MDS,” said Olatoyosi Odenike, MD, FASCO, ASCO Expert.

People with lower-risk myelodysplastic syndromes (MDS) who received luspatercept (Reblozyl^®) to treat anemia instead of erythropoiesis-stimulating agents (ESAs), the current standard of care, needed fewer blood transfusions and clinic visits.

Study at a Glance

Key Findings

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 participants were divided into two groups: 178 received luspatercept by injection once every 3 weeks for at least 24 weeks, and 176 received epoetin α (an ESA) 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 α, there were 301 participants included in the planned interim data analysis. The primary endpoint of this study was transfusion independence for ≥12 weeks with 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 people receiving luspatercept achieved this endpoint, compared to 31.2% of those receiving epoetin α.

The secondary endpoints in the study included hematologic improvement-erythroid (HI-E) response ≥8 weeks and transfusion independence at 24 weeks and ≥12 weeks. HI-E response is an indicator of how much hemoglobin is increased in the blood. Better HI-E responses can suggest that a person may be developing less reliance on transfusions or require fewer transfusions. Across these endpoints, luspatercept was more effective than epoetin α: 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 α. This is important, as ESAs have been the first-line treatment for patients with lower-risk MDS for decades,” said lead author Guillermo Garcia-Manero, MD, professor in the Department of Leukemia and chief of the Section of Myelodysplastic Syndromes at The University of Texas MD Anderson Cancer Center in Houston, Texas. “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 (164 patients, 92.1%) than those who received epoetin α (150 patients, 85.2%). These led 8 (4.5%) people in the luspatercept group and 4 (2.3%) people in the epoetin α group to stop treatment. More participants receiving luspatercept reported treatment-related adverse events than those receiving epoetin α (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%), shortness of breath (dyspnea, 3.4%), and high blood pressure (hypertension, 3.4%). There were 4 (2.2%) participants receiving luspatercept and 5 (2.8%) participants receiving epoetin α whose disease progressed to acute myeloid leukemia (AML). Overall death rates were comparable between both treatment groups (18% luspatercept vs. 18.2% epoetin α).

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. Luspatercept is an erythroid maturation agent that helps the bone marrow grow erythroid cells (which are immature red blood cells) into functional, mature red blood cells.

About the Study

The open-label, randomized phase III trial included participants from more than 20 countries. Participants in this study were adults aged 18 years and older. 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.

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.