Luspatercept appears to be well tolerated and efficacious in patients with red blood cell (RBC) transfusion-dependent, lower-risk myelodysplastic syndromes (LR-MDS) with ring sideroblasts (RS), according to results from the ongoing MEDALIST study (ClinicalTrials.gov Identifier: NCT02631070) published in The New England Journal of Medicine.

The MEDALIST study is a phase 3, randomized, double-blind, placebo-controlled trial. Eligible adult patients had very-low-, low-, or intermediate-risk MDS with RS. They were also refractory or ineligible for erythropoiesis-stimulating agents (ESAs) and RBC transfusion dependent.

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Patients were randomly assigned 2:1 to receive luspatercept (1.0 mg/kg titrated up to 1.75 mg/kg) or placebo subcutaneously every 3 weeks. The primary end point was RBC transfusion independence (TI) for at least 8 weeks in weeks 1 through 24. A key secondary endpoint was RBC-TI for at least 12 weeks in weeks 1 through 24 and 1 through 48.

A total of 229 patients with a median age of 71 years (range, 26-95) were enrolled (men, 63%); 153 were assigned to receive luspatercept and 76 to receive placebo. RBC-TI for at least 8 weeks was observed in 38% and 13% of patients in the luspatercept and placebo groups, respectively (P <.001). Similarly, RBC-TI for at least 12 weeks was observed in more patients in the luspatercept group compared with the placebo group during both weeks 1 through 24 (28% vs 8%) and weeks 1 through 48 (33% vs 12%; P <.001 for both).


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The most common luspatercept-associated adverse events of any grade included fatigue (27%), diarrhea (22%), asthenia (20%), nausea (20%), and dizziness (20%). The researchers noted that the incidence of adverse events decreased with time. Of those receiving luspatercept, 5% had a dose reduction due to adverse events. Equal proportions of patients receiving luspatercept and placebo (8% for both) discontinued treatment due to adverse events.

“Luspatercept significantly reduced the transfusion burden in a substantial proportion of these patients and was associated with mainly low-grade toxic effects,” the researchers concluded.

Reference

1.     Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes [published online January 9, 2020]. N Engl J Med. doi:10.1056/NEJMoa1908892