Abstract: EP798

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Anemic patients with LR-MDS and baseline HTB have very few treatment options and constitute a patient population with significant clinical unmet need. MEDALIST is an ongoing randomized, placebo-controlled, phase 3 study evaluating the efficacy and safety of luspatercept, a first-in-class erythroid maturation agent, for treatment of anemia in patients with LR-MDS (Fenaux P & Platzbecker U, et al. N Engl J Med. 2020;382:140-51; NCT02631070).

Aims
In this secondary analysis of the MEDALIST trial, we sought to evaluate the clinical benefit of luspatercept in patients with LR-MDS and HTB.

Methods
Eligible patients were aged ≥18 years; had Revised International Prognostic Scoring System-defined Very low-, Low-, or Intermediate-risk MDS with ring sideroblasts (RS); were refractory, intolerant, or unlikely to respond to erythropoiesis-stimulating agents (serum erythropoietin >200 U/L); and had anemia requiring regular red blood cell (RBC) transfusions (≥2 units/8 weeks in the 16 weeks prior to randomization). All patients provided informed written consent. 229 patients were randomized 2:1 to luspatercept (starting dose 1.0 mg/kg; titration up to 1.75 mg/kg allowed) or placebo subcutaneously every 3 weeks. HTB was defined as ≥6 RBC units transfused/8 weeks.

Results
153 patients were randomized to luspatercept and 76 to placebo; 66 and 33 of them respectively had HTB at baseline. As of July 1, 2019, 23/66 (34.8%) and 12/66 (18.2%) HTB patients receiving luspatercept achieved a ≥50% and ≥75% reduction from baseline in RBC transfusion burden over ≥24 weeks, respectively, vs 3/33 (9.1%; P=0.0063) and 1/33 (3.0%; P=0.0363) patients receiving placebo. 6/66 (9.1%) luspatercept-treated HTB patients and 1/33 (3.0%) placebo-treated HTB patient achieved RBC‑transfusion independence (TI) ≥8 weeks in Weeks 1–24 (P=0.2699). The median (range) time to achieve RBC-TI with luspatercept was 50.0 days (1.0–100.0) and median (range) duration of RBC-TI in the luspatercept arm was 42.6 weeks (8.4–81.1). Mean number of transfusion events in Weeks 1–24 was 9.2 in the luspatercept arm vs 12.4 in the placebo arm (hazard ratio 0.794; 95% confidence interval 0.660–0.956).

65/66 (98.5%) luspatercept- and 29/33 (87.9%) placebo-treated HTB patients reported ≥1 treatment-emergent adverse event (TEAE); 11/66 (16.7%) and 3/33 (9.1%) patients, respectively, reported ≥1 TEAE leading to discontinuation. 28/66 (42.4%) luspatercept- and 15/33 (45.5%) placebo-treated HTB patients reported ≥1 serious TEAE. Incidence of grade 3–4 TEAEs in HTB patients was similar between arms (53.0% luspatercept vs 54.5% placebo).

Conclusion
Luspatercept treatment resulted in clinically significant reductions in transfusion burden and reduced number of transfusion events in HTB patients with LR-MDS with RS. Luspatercept was well tolerated in HTB patients, consistent with the overall study population.

Session topic: 10. Myelodysplastic syndromes - Clinical

Keyword(s): Clinical trial, MDS, Phase III