The following article features coverage from the American Society of Hematology (ASH) 2018 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

SAN DIEGO — Treatment with luspatercept, a first-in-class erythroid maturation agent, in patients with lower-risk myelodysplastic syndrome with ring sideroblasts lead to a significant reduction in transfusion burden and was well-tolerated 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 ( 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).

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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.

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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.

Read more of Cancer Therapy Advisor‘s coverage of the ASH 2018 meeting by visiting the conference page.


  1. 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.
  2. 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.

This article originally appeared on Cancer Therapy Advisor