The FDA approved the first and only erythroid maturation agent, luspatercept-aamt (Reblozyl), to treat anemia in patients with lower-risk myelodysplastic syndromes (MDS), according to Bristol Meyers Squibb, the agent’s manufacturer.1
In particular, luspatercept is approved to treat anemia failing an erythropoiesis stimulating agent (ESA) and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts (MDS-RS) or with MDS/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).
“(This) approval of Reblozyl is an important milestone for a majority of patients with myelodysplastic syndromes who have limited treatment options to address anemia associated with their disease. It also demonstrates our continued commitment to develop innovative products that improve the lives of patients living with serious diseases,” Diane McDowell, MD, vice president, Hematology Global Medical Affairs, Bristol Myers Squibb, said in a press release. “We are looking forward to making Reblozyl immediately available for this patient population.”
The agency based its approval on data from the double-blind, placebo-controlled, phase III MEDALIST trial, designed to evaluate luspatercept compared with placebo in 229 patients who were categorized with International Prognostic Scoring System (IPSS)-Revised very low-, low-, or intermediate-risk MDS-RS and required RBC transfusions.2
Patients were randomized to receive luspatercept at a dose of 1.0 to 1.75 mg/kg (n = 153) or placebo (76) subcutaneously every 3 weeks.
Results were published in the New England Journal of Medicine in January.
Treatment with luspatercept reduced the severity of anemia in patients with very low- to intermediate-risk MDS-RS who require RBC transfusions. Additionally, the benefit with luspatercept extended to patients with refractory disease or those who were unlikely to respond to or were intolerant of ESAs.
The findings showed that 38% of patients in the luspatercept group had RBC-transfusion independence (RBC-TI) for ≥8 weeks compared with 13% of those in the placebo group (P <.001), meeting the primary endpoint of the study.
In addition, a higher percentage of those treated with luspatercept met the key secondary end point of RBC-TI for weeks 1 through 24 (28% vs. 8%; P < 0.001) and for weeks 1 through 48 (33% vs. 12%; P < 0.001), compared with placebo.
The most common treatment-related adverse events from luspatercept included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time.
“In clinical trials, Reblozyl has shown to have significant benefit for the treatment of anemia in patients with myelodysplastic syndromes who have ring sideroblasts,” Guillermo Garcia-Manero, MD, professor and chief of Section of Myelodysplastic Syndromes, Department of Leukemia, University of Texas MD Anderson Cancer Center, said in the release. “Anemia is a serious consequence of MDS, requiring the majority of these patients to receive regular red blood cell transfusions, which can lead to additional complications, such as iron overload, transfusion site reactions and infections. In our current environment, we are reminded of the significant burden frequent blood transfusions can have on individuals and the healthcare system.”
1. U.S. Food and Drug Administration (FDA) Approves Reblozyl® (luspatercept-aamt), the First and Only Erythroid Maturation Agent, to Treat Anemia in Adults with Lower-Risk Myelodysplastic Syndromes (MDS). Published April 3, 2020. https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-fda-approves-reblozyl-luspater. Accessed April 3, 2020.
2. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Eng J Med. 2020;382(2):140-151. doi: 10.1056/NEJMoa1908892.