COMMANDS Trial: Luspatercept Efficacy in MDS Anemia Superior to Epoetin Alfa

In the phase III COMMANDS clinical trial, luspatercept was compared with epoetin alfa to manage anemia in patients with myelodysplastic syndromes (MDS). The primary analysis of this international, open-label, randomized trial, published in The Lancet Haematology, found luspatercept to have superior efficacy.

“Luspatercept represents a new standard of care for [erythropoiesis-stimulating agent (ESA)]-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes,” wrote lead author Matteo Giovanni Della Porta, MD, of IRCCS Humanitas Research Hospital in Milan, Italy.

The total patient cohort in COMMANDS was 363 ESA-naive adults with transfusion-dependent, very low- to intermediate-risk MDS. It had a median patient age of 74 years, was 45% female, and 80% White. Following randomization, 182 patients received subcutaneous luspatercept once every three weeks and 181 patients received subcutaneous epoetin alfa once weekly.

The primary endpoint used in COMMANDS to compare the two therapies was red blood cell transfusion independence, which persisted for at least 12 weeks and included a mean hemoglobin increase of at least 1.5 g/dL over 24 weeks in the study. This endpoint was reached by 60% of patients who received luspatercept and 35% of patients who received epoetin alfa.

“Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups,” described Dr. Della Porta.

Regarding occurrences of grade 3 to 4 treatment-emergent adverse events in the luspatercept safety cohort, 10% of patients experienced hypertension, 10% anemia, 5% pneumonia, 5% syncope, 5% neutropenia, 4% thrombocytopenia, 4% dyspnea, and 3% MDS. In the epoetin alfa safety cohort, 8% experienced anemia, 8% pneumonia, 6% neutropenia, 6% MDS, 4% hypertension, 4% iron overload, and 3% COVID-19 pneumonia.

The most common serious treatment-emergent adverse event in both groups was pneumonia, at 5% prevalence in the luspatercept group and 7% in the epoetin alfa group. The second most frequent was COVID-19, which affected 4% in the luspatercept group and 6% in the epoetin alfa group.

At interim analysis, there was one mortality in the luspatercept group due to acute myeloid leukemia attributed to the treatment.

The COMMANDS trial was funded by Celgene and Acceleron Pharma.

Reference

Della Porta MG, Garcia-Manero G, Santini V, et al. Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial. Lancet Haematol. 2024;11(9):e646-e658. doi:10.1016/S2352-3026(24)00203-5