Luspatercept Reduces Transfusion Dependence, Improves Erythroid Responses in MDS

Luspatercept performed better than placebo in achieving erythroid responses and reducing transfusion dependence in patients with myelodysplastic syndromes (MDS), according to longer-term results from the double-blind, phase III MEDALIST study.

Amer Zeidan, MBBS, MHS, of the Yale School of Medicine and Yale Cancer Center, and colleagues conducted the study. The investigators recently published the longer-term results in Blood.

The study included patients who had anemia due to lower-risk MDS with ring sideroblasts and received regular red blood cell (RBC) transfusions. The patients were refractory to, intolerant of, or unlikely to respond to erythropoiesis-stimulating agents. None of the patients previously received a disease-modifying agent.

The median follow-up was 26.4 months for patients treated with luspatercept (n=153) and 26.1 months for patients treated with placebo (n=76).

Significantly more patients receiving luspatercept (45.1%) achieved RBC-transfusion independence for eight or more weeks during weeks one through 48 than patients receiving placebo (15.8%; P<.0001). A significantly higher proportion of patients receiving luspatercept (34.6%) than patients receiving placebo (6.6%) achieved at least a 75% reduction in RBC transfusion burden over 24 or more weeks (P<.001).

During weeks one through 48, significantly more patients receiving luspatercept (58.8%; 95% CI, 50.6-66.7) achieved a modified hematologic improvement-erythroid response than patients receiving placebo (17.1%; 95% CI, 9.4-27.5; P<.001).

A higher proportion of patients who received luspatercept (46.4%) reported adverse events of any grade than patients who received placebo (32%). The most common any-grade adverse events in patients treated with luspatercept were fatigue (30.1%) and diarrhea (28.1%).

More than a quarter of patients treated with luspatercept continued treatment for more than two years, “supporting its long-term benefit,” according to the investigators.

“In conclusion, luspatercept had a generally acceptable and predictable safety profile while affording sustained periods of [transfusion independence] and effectively reducing transfusion burden among [high transfusion burden] and [low transfusion burden] patients, contributing to maintaining or improving patient quality of life,” the authors wrote.

Zeidan AM, Platzbecker U, Garcia-Manero G, et al. Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts. Blood. 2022. doi:10.1182/blood.2022016171