Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy (ICT) in Adult Patients (Pts) with β-Thalassemia in the Believe Trial

▪ Introduction: Regular red blood cell (RBC) transfusions are the main supportive treatment for chronic anemia due to β-thalassemia. Transfusion-dependent pts require ICT to prevent iron overload from RBC transfusions, and associated complications. Thus, there is a clinical need to reduce transfusions and iron burden in pts with anemia due to β-thalassemia. Luspatercept, an erythroid maturation agent, is approved by the FDA for treatment of anemia in adult pts with β-thalassemia who require regular RBC transfusions. The phase 3, double-blind, randomized, placebo (PBO)-controlled BELIEVE study is evaluating the efficacy and safety of luspatercept in adult pts with β-thalassemia requiring regular RBC transfusions (NCT02604433; Cappellini MD, et al. N Engl J Med 2020;382:1219-31). Here we assess the effect of long-term luspatercept use on iron loading and ICT use in the BELIEVE trial. Methods: Pts were ≥ 18 years with β-thalassemia or hemoglobin (Hb) E/β-thalassemia (compound β-thalassemia mutation and/or multiplication of α-globin genes was allowed) and required regular RBC transfusions (defined as 6-20 RBC units in the 24 wks prior to randomization with no transfusion-free period > 35 days). Pts were randomized 2:1 to luspatercept 1.0 mg/kg (up to 1.25 mg/kg allowed) or PBO subcutaneously every 3 wks for ≥ 48 wks. Pts in both treatment arms continued to receive RBC transfusions to maintain target pretransfusion Hb levels, as well as ICT (deferasirox, deferoxamine, and deferiprone alone or in combination) per product label and physician practice prior to randomization. After study unblinding, pts randomized to PBO were eligible to cross over to luspatercept in an open-label phase. Risk for iron overload-related complications was evaluated by stratifying pts into categories based on serum ferritin (SF) level (< 1,000 μg/L, 1,000 to < 2,500 μg/L, ≥ 2,500 μg/L), liver iron concentration (LIC; ≤ 3 mg/g dw, > 3 mg/g dw), and myocardial iron (by T2* MRI; ≤ 20 ms, > 20 ms). Long-term changes in SF and ICT use were assessed in luspatercept pts remaining on treatment up to data cutoff (July 1, 2019) or study discontinuation, whichever was earlier. Results: Of 336 pts enrolled, 224 were randomized to luspatercept and 112 to PBO. Mean baseline SF, LIC, and myocardial T2* for luspatercept vs PBO arms were 2,097 vs 1,845 μg/L, 12.0 vs 10.1 mg/g dw, and 33.5 vs 34.8 ms, respectively. Overall, 97.3% of pts received ICT at baseline. As of July 1, 2019, 67.9% of pts initiall