MDS-179: Clinical Benefit of Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes (LR-MDS) and High Transfusion Burden (HTB) in the Phase 3 MEDALIST Study

Background: Patients with LR-MDS and anemia who have HTB have very few treatment options and represent a patient population with significant clinical unmet need. Aims: To evaluate the clinical benefit of luspatercept in HTB patients with LR-MDS from the MEDALIST trial. Methods: Eligible patients were aged ≥18 years; had IPSS-R-defined LR-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 RBC transfusions. 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 had HTB at baseline, respectively. As of 01 JULY, 2019, 23/66 (34.8%) and 12/66 (18.2%) luspatercept-treated HTB patients achieved a ≥50% and ≥75% reduction in RBC units transfused over at least 24 weeks compared to baseline, respectively, versus 3/33 (9.1%; P=0.0063) and 1/33 (3.0%; P=0.0363) HTB placebo patients. 6/66 (9.1%) luspatercept-treated HTB patients and 1/33 (3.0%) placebo-treated HTB patient achieved RBC-transfusion independence (RBC-TI) ≥ 8 weeks in Weeks 1–24 (P=0.2699). Median (range) time to achieve RBC-TI was 50.0 days (1.0–100.0) with luspatercept; median (range) duration of longest RBC-TI episode in luspatercept-treated patients was 42.6 weeks (8.4–81.1). Mean number of transfusion events in Weeks 1–24 was 9.2 for luspatercept-treated patients versus 12.4 in the placebo arm (hazard ratio [95% confidence interval] 0.794 [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 patients reported ≥1 serious TEAE. The incidence of grade 3–4 TEAEs in HTB patients was similar between treatment arms (53.0% for luspatercept vs 54.5% for placebo). Conclusions: HTB patients with LR-MDS with RS receiving luspatercept had clinically significant reductions in RBC transfusion burden and reduced number of transfusion events. Luspatercept was well tolerated in HTB patients, consistent with the overall study population.