SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.
Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.
And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.
Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.
Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.
The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).
A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.
The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).
The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).
The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).
The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).
“This was a very clean drug and a very safe drug,” Dr. List said.
The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.
The PACE study also included a small number of patients who had not previously received an ESA.
Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.
Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.
“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.
The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.
Dr. List reported research funding from Celgene.