In the prespecified interim analysis of the COMMANDS trial for low-risk myelodysplastic syndromes, luspatercept had statistically significant and clinically meaningful improvements in red blood cell transfusion independence with no new safety signals.
The phase 3 COMMANDS trial (NCT03682536) evaluating luspatercept-aamt (Reblozyl) as frontline treatment for patients with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) who require red blood cell (RBC) transfusions demonstrated a highly statistically significant and clinically meaningful improvement in RBC transfusion independence with concurrent hemoglobin increase, meeting the study's primary end point.1
These data were based on a prespecified interim analysis conducted through an independent review committee.
The safety results were also consistent with the safety profile which luspaterceptdemonstrated in a previous study, MEDALIST (NCT02631070). Further, no new safety signals were reported, according to Bristol Myers Squibb.
“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,” said Noah Berkowitz, MD, PhD, senior vice president, Hematology Development, Bristol Myers Squibb, 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 a first-in-class erythroid maturation agent which enhances late-stage erythropoiesis. Currently, the agent has FDA and European Medicines Agency indications for the treatment of patients with lower-risk myelodysplastic syndrome (LR-MDS).
Specifically in April 2020, the FDA granted approval to luspatercept for the treatment of anemia failing an erythropoiesis-stimulating agent and requiring 2 or more RBC units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblastsor with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.
This approval was based on overall findings from the phase 3 MEDALIST trial, which revealed luspatercept to significantly reduce transfusion burden compared with placebo in patients with LR-MDS.
In the phase 3, open-label, randomized COMMANDS study, investigators looked to assesses the efficacy and safety of luspatercept compared with epoetin alfa, for the treatment of patients with anemia due to very low-, low- or intermediate-risk MDS who are RBC transfusion dependent and were erythropoiesis stimulating agent naïve.2
To be eligible for enrollment, adult patients must have had a documented diagnosis of MDS, according to WHO 2016 classification that meets revised international prognostic scoring system classification of very low, low, or intermediate risk disease, have < 5% blasts in bone marrow, an endogenous serum erythropoietinlevel of < 500 U/L, and an ECOG performance status of 0, 1, or 2. Patients were required to have RBC transfusions, consisting of an average transfusion requirement of 2 - 6 units/8 weeks of packed red blood cells confirmed for a minimum of 8 weeks immediately preceding randomization.
The primary end point of the trial was RBC transfusion independence for 12 weeks with a mean hemoglobin increase ≥ 1.5 g/dL. Key secondary end points consisted of RBC transfusion independence for 24 weeks, RBC transfusion independence ≥12 weeks, and erythroid response of at least 8 weeks during weeks 1-24 of the study.
Other end points included mean hemoglobin change over 24 weeks, hematologic improvement, time to first RBC transfusion, RBC transfusion burden on treatment, safety, pharmacokinetics, frequency of antidrug antibodies, number and percentage of participants progressing to acute myeloid leukemia (AML), time to AML progression, and overall survival.
A full evaluation of data from the COMMANDS trial will be presented at an upcoming medical meeting.