Dr. Pierre Fenaux, of Hôpital Saint Louis, Paris and lead author of the MEDALIST trial, told Ash Clinical News that treatment with the investigational drug, luspatercept, improved the rate of blood cell transfusion independence in trial participants. Results of the phase III trial, (NCT02631070), were published in the New England Journal of Medicine.
The trial involved 229 patients with myelodysplastic syndrome with ring sideroblasts (RARS). The studies were held at sixty-five sites located in eleven countries.
Patients ranged from twenty-six years of age to ninety-three years of age (median age was 71).
Dr. Fenaux explained that treatments used in studies for these patients have initially been red blood cell (RBC) transfusions. He went on to explain that this type of treatment requires chelating agents to avoid iron overload. In doing so however, patients tend to experience fatigue and a lower quality of life. Dr. Fenaux said that for this reason treatments that avoid RBC transfusions are preferable.
Almost half of the patients in the MEDALIST trial had received chelation therapy previously.
The MEDALIST TRIAL
Results of the MEDALIST trial were favorable. Adverse events caused by the administration of luspatercept were low-grade and as a result, only a few patients had to discontinue treatment.
The WHO classifies RARS, a subtype of MDS, as over fifteen percent ring sideroblasts contained in bone marrow. RARS is one of a group of refractory anemia that are characterized by inadequate production of blood cells in the bone marrow. The blood cells do not mature properly and often die before leaving the marrow.
Either a placebo or luspatercept were subcutaneously (injected under the skin) every three weeks.
The primary endpoint of the trial was transfusion independence for eight weeks or more during the first to the twenty-fourth weeks. This goal was met.
The secondary endpoint sought transfusion independence from weeks twenty-four through forty-eight.
Results of the study showed that during treatment, about sixty-two patients who received luspatercept experienced a minimum of two transfusion independent intervals lasting for eight weeks. Patients in the placebo group responded with two or less intervals.
The most common adverse events with the luspatercept group were fatigue, asthenia (weakness), diarrhea, nausea and dizziness.
Results of the MEDALIST trial showed that forty percent of trial participants diagnosed with sideroblastic lower-risk MDS were RBC transfusion independent.
Twenty-five to thirty percent of nonsideroblastic patients were also transfusion independent. Side effects were limited.
In conclusion, Dr. Finaux suggests that more trials are needed to study the effects of increasing the dose or the frequency of luspatercept in the treatment of anemia involving patients with low risk MDS with ring sideroblasts or treatment of nonsideroblastic patients.
