Dr Platzbecker on the FDA Approval of Luspatercept in Lower-Risk MDS

Uwe Platzbecker, MD, director, Medical I, University Hospital Leipzig, discusses the significance of the FDA approval of luspatercept-aamt (Reblozyl) for patients with lower-risk myelodysplastic syndrome (MDS) with anemia.

On August 28, 2023, the FDA approved luspatercept for the treatment of anemia in patients with very low- to intermediate-risk MDS who are naïve to erythropoiesis-stimulating agents (ESAs) and who may require regular red blood cell (RBC) transfusions. This regulatory decision was supported by findings from the phase 3, open-label, randomized COMMANDS trial (NCT03682536), which enrolled patients with lower-risk MDS who were stratified by baseline RBC transfusion burden, endogenous serum erythropoietin concentration, and ring sideroblast status. Patients in the luspatercept arm received luspatercept subcutaneously once every 3 weeks at a stating dose of 1.0 mg/kg, with possible titration up to 1.75 mg/kg. Patients in the epoetin alfa arm received epoetin alfa subcutaneously once weekly at a starting dose of 450 IU/kg, with possible titration up to 1050 IU/kg and a maximum permitted dose of 80,000 IU.

In COMMANDS, 59% of patients who received luspatercept achieved RBC transfusion independence for at least 12 weeks vs 31% of those who received the ESA epoetin alfa (common risk difference on response rate, 26.6; 95% CI, 15.8-37.4; P < .0001). In addition, the median length of treatment exposure was longer in the luspatercept arm, at 42 weeks (interquartile range, 20-73) compared with 27 weeks (interquartile range, 19-55) in the epoetin alfa arm.

The most common treatment-emergent adverse effects (AEs) observed with luspatercept included anemia, hypertension, dyspnea, neutropenia, thrombocytopenia, COVID-19, pneumonia, MDS, and syncope. The most common suspected treatment-related AEs observed with luspatercept were fatigue, nausea, asthenia, dyspnea, headache, and hypertension.

This approval of luspatercept brings a novel choice of first-line therapy to patients with lower-risk MDS who are naïve to epoetin alfa and RBC transfusion dependent, Platzbecker says. Luspatercept has changed the treatment landscape for this patient population as the first drug to show superiority over epoetin alfa, which was the previous first-line standard of care, Platzbecker concludes.

Editor’s Note: This interview was conducted prior to the FDA approval of luspatercept in patients with lower-risk MDS with anemia.