Luspatercept Reduced RBC Transfusion Dependence in Lower-Risk Patients With Myelodysplastic Syndromes
Findings from the MEDALIST trial revealed a significant reduction in transfusion burden for patients being treated with luspatercept compared with placebo
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SAN DIEGO — Treatment with luspatercept, a first-in-class erythroid maturation agent, in patients with lower-risk myelodysplastic syndrome with ring sideroblasts, led to a significant reduction in transfusion burden and was well-tolerated by patients, according to results of a study presented in the plenary session at the 2018 American Society of Hematology Annual Meeting in San Diego, California.1 The findings of the MEDALIST trial, a phase 3 randomized, double-blind, placebo-controlled study (ClinicalTrials.gov Identifier: NCT02631070) were presented by Allen F. List, MD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida.1
For the trial, researchers enrolled 229 patients from a total of 65 centers in Europe, the United States, and Canada. The researchers used the Revised International Prognostic Scoring System to define very low-, low-, or intermediate-risk disease and patients were randomly assigned 2:1 to receive either luspatercept 1.0 mg/kg subcutaneously every 21 days (with escalation up to 1.75 mg/kg, if needed; 153 patients) or placebo every 21 days (76 patients) for 24 weeks or more. Patients had a median age of 71 years (range, 26 to 95) and 62.9% were male. The median time from diagnosis for enrolled patients was 41.8 months (range, 3 to 421).
The patients were administered a median of 5 red blood cell (RBC) units (range, 1-20) across 8 weeks in the 16 weeks leading up to treatment. Serum erythropoietin levels were less than 200 IU/L in 138 patients (60.3%), 200 IU/L to 500 IU/L in 58 patients (25.3%), and greater than 500 IU/L in 32 patients (14.0%). There were 218 patients (95.2%) who had received a previous erythropoiesis-stimulating agent and 90% of patients within the trial had an SF3B1 mutation.
The primary end point of the study was RBC transfusion independence for 8 weeks or longer, which was met by 58 patients in the luspatercept arm (37.9%; 95% CI, 30.2-46.1) and 10 patients in the placebo arm (13.2%; 95% CI, 6.5-22.9; P < .0001). The secondary end point of the study was red blood cell transfusion independence for 12 weeks or longer (in weeks 1 to 24), which was achieved in 43 of the 153 patients receiving luspatercept (28.1%) compared with 6 of the 76 patients in the placebo arm (7.9%; OR 5.1; P = .0002).
In addition to these findings, the researchers reported that modified hematologic improvement-erythroid response using International Working Group 2006 criteria (which was defined as a reduction in transfusion by 4 or more RBC units every 8 weeks or a mean hemoglobin increase of 1.5 g/dL or more every 8 weeks with no transfusion) occurred more frequently in patients in the luspatercept arm compared with patients in the placebo arm (52.9% vs 11.8% during weeks 1 to 24; P < .0001).
The safety profile of luspatercept was similar to previously reported data from the phase 2 PACE-MDS study.2 The most common treatment-emergent adverse events in patients receiving luspatercept were fatigue (26.8%), diarrhea (22.2%), asthenia (20.3%), nausea (20.3%), and dizziness (19.6%). In patients receiving placebo, the most commonly reported adverse events included peripheral edema (17.1%), fatigue (13.2%), cough (13.2%), asthenia (11.8%), and fall (11.8%).
“In lower-risk, ring sideroblast-positive myelodysplastic syndromes, treatment with luspatercept resulted in a significantly higher percentage of patients who achieved RBC-transfusion independence, major RBC transfusion reduction, or hemoglobin increase compared with placebo,” concluded Dr List. “Luspatercept is a potential new therapy for the treatment of [these patients].”
Disclosures: This research was funded by Celgene. Multiple authors declare affiliations with the pharmaceutical industry. For a complete list of disclosures please refer to the original abstract.
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- Fenaux P, Platzbeck U, Mufti GJ, et al. The Medalist Trial: results of a phase 3, randomized, double-blind, placebo-controlled study of luspatercept to treat anemia in patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts (RS) who require red blood cell (RBC) transfusions. Oral plenary presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 1.
- Platzbecker U, Germing U, Götze KS, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017;18:1338-1347.