Luspatercept Reduces Transfusion Burden Compared With Epoetin Alfa


Individuals with very low- to intermediate-risk myelodysplastic syndromes treated with luspatercept (Reblozyl; Bristol Myers Squibb) achieved improvements in hemoglobulin levels.

New data from the COMMANDS (NCT03682536) trial showed that a greater proportion of individuals with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) who were treated with luspatercept (Reblozyl; Bristol Myers Squibb) achieved improvements in hemoglobulin (Hb) levels and reductions in transfusion burden and red blood cell unit transfusions compared with individuals treated with epoetin alfa, according to an abstract from the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting.1

Hematology, MDS, Red Blood Cell | Image Credit: ImageFlow -

Image Credit: ImageFlow -

Individuals included in the study were aged 18 years or older, had low-risk MDS with or without ring sideroblasts and less than 5% bone marrow blasts, and endogenous serum erythropoietin less than 500 U/L. Further, patients included also required RBC transfusions and were erythropoiesis-stimulating agent naïve, according to the authors.1

Treatment was randomized to subcutaneous administration of luspatercept every 3 weeks at 1.0 to 1.75 mg/kg or epoetin alfa (450 to 1050 IU/kg) once weekly for 24 weeks or more. In the new data presented at ASCO, investigators included achievement and duration of 50% or greater reduction in RBC units transfused over 12 weeks or more, transfusion burden, time to first transfusion, achievement and cumulative duration of all separate RBC transfusion independence for 12 weeks or more, and mean Hb increases of 1.5 g/dL or more over weeks 1 and 24.1

As of data available on March 31, 2023, approximately 83% of those who received luspatercept achieved a 50% or greater reduction in RBC transfusion over 12 weeks or more compared with 66.9% with epoetin alfa, with a median duration of 130 and 77 weeks, respectively. Furthermore, regardless of baseline transfusion burden, a greater proportion of individuals receiving luspatercept achieved a 50% reduction in RBC transfusions compared with epoetin alfa at 89% and 73.9% for less than 4 units per 8 weeks, respectively, and 71.9% and 55.7% for 4 or more units per 8 weeks, respectively.1

The median number of RBC units during weeks 1 and 24 for luspatercept was 1 compared with 3 for epoetin alfa. The median time to transfusion was 155 days and 42 days, respectively. For patients who achieved RBC transfusion independence for 12 weeks or greater, 17.7% of individuals receiving luspatercept and 13.6% receiving epoetin alfa achieved 2 or more separate response episodes, according to the abstract authors, with a duration of all response being 147.9 weeks and 95.1 weeks, respectively. The mean Hb increase of 1.5 g/dL or more was achieved by 74.2% and 52.5%, respectively.1

About The Trial

Trial Name: A Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Participants Who Require Red Blood Cell Transfusions and Are ESA Naïve (COMMANDS)

Sponsor: Celgene ID: NCT03682536

Completion Date (Estimated): September 2027

Previously, in 2023, results from the study showed that 58.5% achieved RBC transfusion independence of at least 12 weeks with concurrent mean Hb increases within the first 24 weeks compared with 31.2% with epoetin alfa, according to an article on Pharmacy Times. Additionally, approximately 74.1% achieved erythroid response increase of at least 8 weeks compared with 51.3%, respectively.2

Based on the initial data, the FDA approved the drug as a first-line treatment for anemia in adults without previous administration of an erythropoiesis-stimulating agent with very low- to intermediate-risk MDS who may require regular RBC transfusions.3

1. Zeidan AM, Platzbecker U, Della Porta MG, Santini V, et al. Clinical benefit of luspatercept treatment (tx) in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)–naive patients (pts) with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) in the COMMANDS trial. Journal of Clinical Oncology. May 29, 2024. Accessed June 10, 2024.
2. Gallagher A. Luspatercept-aamt Shows Efficacy Treating Anemia Due to Myelodysplastic Syndromes. Pharmacy Times. June 19, 2023. Accessed June 10, 2024.
3. Pharmacy Times. FDA Approves Luspatercept-aamt for First-Line Treatment of Anemia in Adults With Lower-Risk Myelodysplastic Syndromes. August 29, 2023. Accessed June 10, 2024.
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