A group of international researchers at the ASH annual meeting presented results from the Medalist Trial, which is evaluating the safety and efficacy of luspatercept in patients with myelodysplastic syndrome (MDS).
Luspatercept, a first-in-class erythroid maturation agent (EMA), is believed to regulate late-stage red blood cell maturation. Currently developed by Acceleron Pharma and Celgene Corporation, it is not yet approved for any indications. The recent study results pertain to the drug’s effect on transfusions in patients with anemia due to very low-risk, low-risk, or intermediate-risk MDS (as defined by the Revised International Prognostic Scoring System [IPSS-R]) with ring sideroblasts (RSs) who require red blood cell (RBC) transfusions.
According to lead author Pierre Fenaux, MD, PhD, Hôpital Saint-Louis in Paris, France, and international colleagues, luspatercept significantly reduced transfusion burden compared with placebo in this patient population and was generally well tolerated.
“MDS is associated with an erythroid maturation defect, characterized by ineffective erythropoiesis leading to anemia and RBC transfusion dependence,” the researchers said. “Treatment of anemia in lower-risk MDS remains an unmet medical need.”
The Medalist Trial, a phase III, randomized, double-blind, placebo-controlled study, enrolled patients who:
- were 18 years or older
- had IPSS-R-defined very low-risk, low-risk, or intermediate-risk MDS with RSs according to the World Heath Organization 2016 criteria
- were refractory, intolerant, or ineligible to receive erythropoiesis-stimulating agents (ESAs)
- required RBC transfusions
The study randomized patients (2:1) to luspatercept or placebo subcutaneously every three weeks for at least 24 weeks. Patients had a median age of 71 years (range, 26–95) and a median time since diagnosis of 41.8 months (range, 3–421); 62.9% were male. The authors said other baseline characteristics were similar between the two groups. In the 16 weeks prior to treatment, the patients received a median of five RBC units (range 1–20) over eight weeks.
Of 153 patients receiving luspatercept, 58 (37.9%) achieved the primary endpoint: RBC transfusion independence for eight weeks or more between weeks 1 and 24. Comparatively, 10 of 76 patients (13.2%) receiving placebo achieved the primary endpoint. Additionally, in the luspatercept group, 43 of 153 (28.1%) achieved transfusion independence for 12 weeks or more between weeks 1 and 24, a secondary endpoint of the trial. In the placebo group, 6 of 76 (7.9%) patients reached the secondary endpoint.
Finally, the authors reported that the patients receiving luspatercept were more likely to achieve a modified hematologic improvement-erythroid (mHI-E) response in the absence of transfusions (52.9% versus 11.8%). Luspatercept was well-tolerated, the authors said, with a safety profile similar to previous reports.