Luspatercept as New Standard of Care in Lower-Risk MDS

Compared with epoetin alfa, treatment with luspatercept improved rates of transfusion independence and hematological improvement in significantly more patients with transfusion-dependent lower-risk myelodysplastic syndromes (MDS), according to primary analysis of the phase III COMMANDS trial.

Matteo Giovanni Della Porta, MD, of the Humanitas Research Hospital Cancer Center in Milan, Italy, and lead author of the study, and colleagues published the data in The Lancet Haematology.

From January 2019 to September 2022, the COMMANDS trial randomized 363 erythropoiesis-stimulating agent (ESA)-naïve patients to luspatercept (n=182) or epoetin alfa (n=181). The cohort had a median age of 74 years (interquartile range [IQR], 69-80) and was 55% male.

The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks plus a mean hemoglobin increase of at least 1.5 g/dL from weeks one to 24.

After a median follow-up of 17.2 months (IQR, 10.4-27.7) in the luspatercept group and 16.9 months (IQR, 10.1-26.6) in the epoetin alfa group, 60% (n=110) of patients treated with luspatercept achieved the primary endpoint compared with 35% (n=63) of patients treated with epoetin alfa.

The safety analysis covered a median follow-up of 21.4 months (IQR, 24.1-32.4) in the luspatercept group and 20.3 months (IQR, 12.7-30.9) in the epoetin alfa group.

The most common grade 3 to 4 treatment-emergent adverse events (TEAEs) in the luspatercept group were hypertension (n=19), anemia (n=18), pneumonia (n=10), syncope (n=10), neutropenia (n=9), dyspnea (n=8), and MDS (n=6).

The most common grade 3 to 4 TEAEs in the epoetin alfa group were anemia (n=14), pneumonia (n=14), neutropenia (n=11), MDS (n=10), hypertension (n=8), iron overload (n=7), and COVID-19 pneumonia (n=6).

“Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk MDS,” Dr. Della Porta and colleagues summarized.

Reference

Porta MGD, 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. doi:10.1016/S2352-3026(24)00203-5