Luspatercept-aamt Yields Improved RBC-TI and Hemoglobin Increase Vs Epoetin Alfa in MDS

Topline results from the phase 3 COMMAND trial (NCT03682536) indicated that the use of luspatercept-aamt (Reblozyl) for treating adult patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) produced a clinically meaningful and statistically significant improvement in red blood cell transfusion independence (RBC-TI) and concurrent hemoglobin increases compared with epoetin alfa, according to a press release from Bristol Myers Squibb.¹

Findings from the trial were based on a pre-specified interim analysis that was performed via independent review committee. Data indicated that the safety profile of luspatercept was consistent with previous findings in the phase 3 MEDALIST trial (NCT02631070), with no new safety signals. A full evaluation of the trial data will be presented at an upcoming medical meeting.

“While advancements have been made in the treatment of anemia for patients with myelodysplastic syndromes, there remains a significant need for new and better first-line treatment options for patients with transfusion-dependent MDS,” Noah Berkowitz, MD, PhD, senior vice president of Hematology Development at Bristol Myers Squibb, said in the press release. “We are pleased with the positive results of the COMMANDS study and look forward to presenting these important data.”

Luspatercept is an agent that promotes late-stage red blood cell maturation, and was approved by the FDA in November 2019 for the treatment of anemia in adult patients with beta thalassemia who require recurring red blood cell transfusions, and for those who had anemia after an erythropoiesis stimulating agent had failed in patients with MDS harboring ring sideroblasts in April 2020.^2-3 The treatment is not designated for use as a substitute in patients who require immediate correction of anemia.

The open-label, randomized phase 3 COMMANDS study was designed to evaluate the efficacy and safety of luspatercept compared with epoetin alfa for patients with anemia due to MDS in patients who are red blood cell transfusion dependent and erythropoiesis stimulating agent naïve.

The primary end point of the COMMANDS study was percent of patients who achieved RBC-TI. Secondary end points included percentage of patients requiring RBC-TI, mean hemoglobin increase over 24 weeks, hematologic improvement based on erythroid response, duration of and time to RBC-TI, and overall survival.

Adult patients with a documented diagnosis of MDS with very low-, low-, or intermediate-risk disease based on 2016 World Health Organization classifications and have less than 5% of blasts in bone marrow were eligible to enroll on the trial. Additional inclusion criteria included having an endogenous serum erythropoietin level of under 500 U/L, having red blood cell transfusions with an average transfusion requirement of 2 to 6 units every 8 weeks with packed red blood cells for a minimum 8 weeks prior to randomization, and having an ECOG performance status of 0 to 2. Patients were excluded from the trial if they had clinically significant anemia due to iron, vitamin B12, or folate deficiencies; autoimmune or hereditary hemolytic anemia; hypothyroidism; or any type of known clinically significant bleeding or drug-induced anemia.

References

1. Bristol Myers Squibb announces positive topline results of phase 3 COMMANDS trial. News release. Bristol Myers Squibb. October 31, 2022. Accessed November 1, 2022. http://bit.ly/3gPOHvk
2. FDA Approves REBLOZYL® (luspatercept-aamt) for the Treatment of Anemia in Adults With Beta Thalassemia Who Require Regular Red Blood Cell Transfusions. News release. Celgene. November 8, 2019. Accessed November 1, 2022. http://bit.ly/3DQGiRz
3. U.S. Food and Drug Administration (FDA) Approves Reblozyl® (luspatercept-aamt), the First and Only Erythroid Maturation Agent, to Treat Anemia in Adults with Lower-Risk Myelodysplastic Syndromes (MDS). News release. Bristol Myers Squibb. April 3, 2022. Accessed November 1, 2022. http://bit.ly/3sMLWh5