Clinical Perspectives

Drug Increases Red Blood Cell Production, Reduces Transfusion Burden in Patients with Myelodysplastic Syndromes

December 08, 2014

Drug Increases Red Blood Cell Production, Reduces Transfusion Burden in Patients with Myelodysplastic Syndromes.jpg

An Open-Label, Phase 2, Dose-Finding Study of Sotatercept (ACE-011) in Patients with Low or Intermediate-1 (Int-1)-Risk Myelodysplastic Syndromes (MDS) or Non-Proliferative Chronic Myelomonocytic Leukemia (CMML) and Anemia Requiring Transfusion

Rami S. Komrokji, MD

Anemia is the most challenging complication of myelodysplastic syndromes (MDS), one of the most common blood cancers. Treatment of anemia in MDS remains an unmet need. Among several investigational treatments that aim to promote RBC growth is sotatercept (ACE-011), a drug that has shown efficacy in healthy volunteers Phase I trials. This drug, an injectable activin type IIa receptor fusion protein, is designed to attach to a molecule that inhibits erythrocyte (immature RBC) production.

This was the first study to test sotatercept in MDS patients; researchers enrolled 54 largely transfusion-dependent patients with MDS who had not responded to treatment with erythrocyte-stimulating agents (ESAs) and other available MDS treatments in a Phase II dose finding clinical trial. The treatment was administered once every three weeks for four doses, which were to be continued among responders. Forty five percent of evaluable patients experienced a reduced need for transfusions or an increase in hemoglobin levels. In addition, a majority of the patients whom were considered to be highly transfusion-dependent (19 of 44) showed a reduced need for transfusions, and 11% became RBC transfusion independent. Of those considered less RBC transfusion dependent, a majority (5 of 9) achieved both transfusion independence and increased hemoglobin levels. The treatment was generally well tolerated, with 37 percent of patients reporting one or more treatment-related adverse events.

“This drug shows promise as an agent that may reduce the burden of regular blood transfusions or eliminate its need among anemic, lower risk MDS patients. Importantly, the response rates are more encouraging in our study than most reported with current investigational agents,” said lead study author Rami S. Komrokji, MD, of the H. Lee Moffitt Cancer Center & Research Institute. “Larger and randomized studies are necessary to confirm those promising results and evaluate whether a higher dose may provide greater benefit without additional toxicity.”

As part of the ASH Hematology Annual Conference, Dr. Komrokji presented this study during a poster presentation on Sunday, December 7, 2014 in the Moscone Center. [70373]