SAN DIEGO – A novel erythroid maturation agent significantly reduced transfusion burden versus placebo in patients with anemia caused by myelodysplastic syndromes (MDS) and ringed sideroblasts, results of a randomized, phase 3 trial demonstrate.
Luspatercept was “very well tolerated” and responses were durable, with approximately 40% of patients remaining transfusion free after 1 year of therapy, said, of Moffitt Cancer Center, Tampa.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ringed sideroblasts who are red blood cell transfusion–dependent,” said Dr. List, senior author of thetrial, said in a press conference at the annual meeting of the American Society of Hematology.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
In a separate randomized, placebo-controlled, phase 3 study presented at ASH 2018, Maria Domenica Cappellini, MD, of the University of Milan,that, in beta-thalassemia patients who were transfusion dependent, luspatercept treatment resulted in a statistically significant reductions in transfusion burden versus placebo, and was generally well tolerated.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the transforming growth factor–beta superfamily, which is known to be important in suppressing erythropoiesis in patients with MDS, Dr. List said.
The MDS study included patients with very low–, low-, or intermediate-risk disease and ringed 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 randomly allocated to luspatercept 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 end point was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
A total of 37.9% of luspatercept-treated patients achieved that primary endpoint, compared with 13.2% of placebo-treated patient (P less than .0001), Dr. List reported. The luspatercept-treated patients also had a 52.9% rate of erythroid response, compared with 11.8% in the placebo group (P less than .0001).
There were no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia. “This was a very clean drug and a very safe drug,” he said.
The decision to study luspatercept in patients with ringed sideroblasts was based on results of a large, phase 2 European study showing a higher response rate in that subset of MDS patients, according to Dr. List.
That study also included a small number of patients who had not previously received an ESA. Currentlyis a phase 3 trial looking at luspatercept in ESA-naive, 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, who represent about 25% of patients overall, according to MDS expert, of Dana-Farber Cancer Institute and Harvard Medical School, Boston.
“It’s been 12 years since we had an FDA [Food and Drug Administration]-approved drug in MDS, and there have been seven 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.
Dr. List reported research funding from Celgene.
SOURCE: List AF et al. ASH 2018, .