OBJECTIVES: To assess the longitudinal effects of luspatercept on TB, Hb, SF levels, and ICT usage in the MEDALIST study.

METHODS: Response to luspatercept was defined as red blood cell (RBC) transfusion independence ≥8 weeks (Weeks 1–24). Change from baseline in RBC units transfused, transfusion visits, and Hb and SF levels were assessed every 24 weeks; proportion of patients receiving ICT and ICT dosage every 12 weeks from initiation to data cutoff (1JULY2019) were assessed in patients remaining on treatment after clinical benefit assessment (Week 25).

RESULTS: During Weeks 1–24, RBC units transfused reduced in luspatercept responders (least square mean difference [LSMD] −10.3; 95%CI −12.4, −8.3; P<0.0001) and non-responders (LSMD −2.8; 95%CI −4.9, −0.6; P=0.0135) versus placebo. Number of transfusion visits reduced in luspatercept responders (LSMD −5.9; 95%CI −7.1, −4.7; P<0.0001) and non-responders (LSMD −0.8; 95%CI −1.9, 0.4; P=0.21) versus placebo. 21.4% of luspatercept-treated versus 2.3% of placebo-treated patients with baseline SF ≥1,000 µg/L shifted to <1,000 µg/L (Weeks 1–24). During the study, SF level was reduced (in 21.4% to 40.0% of patients) in patients with baseline SF ≥1,000 µg/L. During Weeks 25–144, versus baseline, luspatercept-treated patients experienced: sustained Hb level increases (mean change ≥1.3 g/dL); reduction in RBC units transfused (LSMD −3.5 to −6.0); and decreased transfusion visits (LSMD −2.0 to −4.4). The proportion of patients receiving ICT did not increase after Week 24 (41.8% vs 31.3%–42.6%); and deferasirox mean dosing decreased (−8.0 to −409.8 mg/d), compared with baseline.

CONCLUSIONS: TB was significantly reduced in luspatercept responders and non-responders versus placebo (Weeks 1–24). Long-term luspatercept treatment was associated with sustained reductions in TB and SF levels, improved Hb levels, and decreased ICT usage.