Luspatercept Improves Transfusion Independence in Very Low– to Intermediate-Risk MDS

Luspatercept generated a statistically significant improvement in red blood cell transfusion independence with concurrent hemoglobin increase vs epoetin alfa in patients with very low–, low-, or intermediate-risk myelodysplastic syndromes who require RBC transfusions, meeting the primary end point of the phase 3 COMMANDS trial.

Luspatercept-aamt (Reblozyl) generated a highly statistically significant and clinically meaningful improvement in red blood cell (RBC) transfusion independence with concurrent hemoglobin increase compared with epoetin alfa in patients with very low–, low-, or intermediate-risk myelodysplastic syndromes (MDS) who require RBC transfusions, meeting the primary end point of the phase 3 COMMANDS trial (NCT03682536).1

Detailed findings of the prespecified interim analysis by an independent review committee will be shared at an upcoming medical meeting and discussed with health authorities.

“While advancements have been made in the treatment of anemia for patients with MDS, 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, stated in a press release. “We are pleased with the positive results of the COMMANDS study and look forward to presenting these important data.”

In April 2020, the FDA approved luspatercept for the treatment of anemia failing an erythropoiesis stimulating agent (ESA) and requiring 2 or more RBC units over 8 weeks in adult patients with very low– to intermediate-risk MDS with ring sideroblasts or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.2 Additionally, in November 2019, the FDA approved luspatercept for the treatment of anemia in adult patients with beta thalassemia who require regular RBC transfusions.3

The open-label, randomized COMMANDS trial evaluated the efficacy and safety of luspatercept vs epoetin alfa in patients with very low–, low-, or intermediate-risk MDS who were RBC transfusion dependent, had less than 5% bone marrow blasts, and were naïve to treatment with an ESA.4

Key inclusion criteria included an endogenous serum erythropoietin level of less than 500 U/L and an ECOG performance status between 0 and 2. To be considered RBC transfusion dependent, patients needed an average transfusion requirement of between 2 and 6 units of packed RBCs, which needed to be confirmed for a minimum of 8 weeks prior to randomization.

Patients were excluded from the trial if they had clinically significant anemia due to iron, B12, or folate deficiencies; autoimmune or hereditary hemolytic anemia; hypothyroidism; any type of known clinically significant bleeding or sequestration or drug-induced anemia; a known history of diagnosis of acute myeloid leukemia; or uncontrolled hypertension.

Enrolled patients were randomly assigned to luspatercept or epoetin alfa. Along with the primary end point of RBC transfusion independence for 12 weeks with a mean hemoglobin increase of at least 1.5 g/dL, secondary end points included RBC transfusion independence for 24 weeks, hemoglobin change over 24 weeks, hematologic improvement, time to first RBC transfusion, quality of life, and safety.

Safety results of COMMANDS were consistent with the safety profile of luspatercept previously demonstrated in the phase 3 MEDALIST trial (NCT02631070), and no new safety signals were reported.

References

  1. Bristol Myers Squibb announces positive topline results of phase 3 COMMANDS trial. News release. Bristol Myers Squibb. October 31, 2022. Accessed October 31, 2022. https://bit.ly/3WuFA3R
  2. 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, 2020. Accessed October 31, 2022. https://bit.ly/2JEHtGG
  3. 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 October 31, 2022. https://bit.ly/33vOhPo
  4. 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). ClinicalTrials.gov. Updated October 26, 2022. Accessed October 31, 2022. https://clinicaltrials.gov/ct2/show/NCT03682536