Encouraging Efficacy Shown With Luspatercept in MDS/MPN-RS-T

December 7, 2020 — Findings from the MEDALIST trial demonstrated encouraging clinical efficacy, as well as a tolerable safety profile, with luspatercept among patients with myelodysplastic syndrome and myeloproliferative neoplasms with ring sideroblasts and thrombocytosis.

This retrospective analysis of the randomized, double-blind phase 3 trial showed that patients administered luspatercept were significantly more likely to achieve red blood cell transfusion independence (RBC-TI) at 64.3% versus 22.2% for patients who received placebo (P = .028). The clinical benefit for luspatercept was 78.6% compared with 33.3% for the placebo (P = .034).

Patients who achieved RBC-TI for at least 8 weeks were more likely to achieve durable RBC-TI for 48 weeks or more, at 28.6% in the luspatercept arm versus 0% in the placebo arm (P = .084).

“[Patients with] low-transfusion burden, defined as less than 4 units over 8 weeks were more likely to achieve RBC-TI for 8 weeks or more than [patients with] high-transfusion burden,” Rami S. Komrokji, MD, from the H. Lee Moffitt Cancer Center and Research Institute, said in his presentation. “But both groups achieved high rates of modified erythroid hematologic improvement.”

White blood cell count was significantly increased with luspatercept from 5.3 × 109/L at baseline to 7.8 × 109/L at 25 weeks. Platelet and absolute neutrophil count also had a trend toward increase with this drug at week 25.

Twenty-three of the 229 patients in MEDALIST had MDS/MPN-RS-T; 14 of these patients received luspatercept and 9 received placebo. There were 10 patients (43.5%) who received less than 4 units of RBC transfusion every 8 weeks, 9 (39.1%) who received 4 to 5 units, and 4 (17.4%) who received 6 or more units. Baseline characteristics were broadly similar between these 2 groups, according to Komrokji.

The primary end point of this analysis was the achievement of RBC-TI for 8 or more weeks during weeks 1 through 24 of the study.

Luspatercept significantly reduced transfusion burden for patients with lower-risk MDS when compared with placebo in the initial results of the MEDALIST study. For the trial, patients were randomized 2:1 to 1 mg/kg of luspatercept subcutaneously every 21 days (N = 153) versus placebo (N = 76).

Patients in this trial had to have at least 15% ring sideroblasts or at least 5% SF3B1 mutation, non-deletion 5q MDS, Revised International Prognostic Score of very low-,

low, or intermediate-risk MDS, prior response to erythropoiesis-stimulating agents (ESA), no prior treatment with disease modifying agents, and average red blood cell transfusion burden of at least 2 units every 8 weeks.

Incidence of any grade treatment-emergent adverse events was higher with luspatercept compared with placebo. In the treatment arm, the most common toxicities were dizziness (50%), nausea (42.9%), and diarrhea (42.9%).. The most common treatment-emergent toxicities observed in the placebo arm were nausea (22.2%), diarrhea (11.1%), and fatigue (11.1%). Despite these, luspatercept was generally well-tolerated.

“MDS/MPN-RS-T represents a unique myeloid disorder characterized by both myelodysplastic and myeloproliferative features,” Komrokji explained. “Anemia represents the main therapeutic challenge for patients with MDS/MPN-RS-T, with up to 50% of patients becoming transfusion dependent.”

“The proportion of patients with MDS/MPN-RS-T that received luspatercept who achieved RBC-TI for 8 weeks or more compared with placebo was comparable to the entire MEDALIST population…these data support the clinical benefit of luspatercept in this patient population with otherwise limited treatment options,” Komrokji concluded.

Luspatercept was approved by the FDA for the treatment of anemia in patients with low-risk MDS or MDS/MPN-RS-T after ESA failure earlier this year.2


  1. Komrokji RS, Platzbecker U, Fenaux P, et al. Efficacy and Safety of Luspatercept Treatment in Patients with Myelodysplastic Syndrome/ Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T): A Retrospective Analysis from the MEDALIST Study. Poster presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 3111. https://bit.ly/39OSpzP
  2. FDA approves luspatercept-aamt foranemia in adults with MDS. News release. FDA. Updated April 6, 2020. Accessed December 7, 2020. https://bit.ly/2VNJCpR