Abstract
MEDALIST (NCT02631070) is a randomized, placebo-controlled, phase 3 trial evaluating efficacy and safety of luspatercept in patients with anemia due to LR-MDS with RS.
To evaluate long-term transfusion burden reduction with luspatercept in MEDALIST trial patients.
Patients were aged ≥18 years; had IPSS-R-defined LR-MDS with RS; were refractory, intolerant, or unlikely to respond to ESAs; and required RBC transfusions (≥2 units/8 weeks in the 16 weeks before randomization). Two hundred twenty-nine patients were randomized 2:1 to luspatercept (1.0 mg/kg, titration to 1.75 mg/kg) or placebo subcutaneously every 3 weeks.
As of 1 July 2019, 77/153 (50.3%) and 11/76 (14.5%) patients receiving luspatercept and placebo, respectively, achieved ≥50% RBC transfusion burden reduction over at least 24 weeks versus baseline (P < 0.0001). Median longest single response episode was 131.6 weeks with luspatercept and not estimable with placebo due to patients stopping treatment. Mean change from baseline in RBC units transfused in Weeks 9–24, was −3.0 (95% CI −3.9, −2.1) versus +0.4 (95% CI −0.6, 1.4) in the luspatercept versus placebo arms; in Weeks 33–48, mean change was −4.9 (95% CI −5.9, −3.9) with luspatercept. Mean transfusion visits in Weeks 1–24 was 5.9 versus 9.5 in the luspatercept versus placebo arms. Mean number (least squares mean [LSM]) of RBC units transfused/48 weeks during Weeks 1–48 was 22.89 (23.28) versus 35.98 (35.20) in the luspatercept versus placebo arms (LSM difference −11.92 [95% CI −15.55, −8.28]; P < 0.0001). Mean (LSM) RBC transfusion events/48 weeks was 12.95 (13.14) versus 19.54 (19.15) in the luspatercept versus placebo arms (LSM difference −6.00 [95% CI −8.16, −3.85]; P < 0.0001). Serum ferritin LSM change from baseline was −2.7 μg/L versus +226.5 μg/L in luspatercept versus placebo arms (LSM difference −229.1 μg/L; P=0.0024) in Weeks 9–24; −72.0 μg/L versus +247.4 μg/L in Weeks 33–48 (LSM difference −319.5 μg/L; P=0.0294). In Weeks 1–24, 38/127 (29.9%) versus 5/65 (7.7%) patients (P=0.0005) achieved major hematologic improvement-erythroid response (per IWG 2018) in the luspatercept versus placebo arms.
Luspatercept demonstrated clinical efficacy in patients with LR-MDS with RS and was associated with significant reductions in RBC transfusions (≥50%) and serum ferritin.