Erythroid maturation agent in patients with β-thalassaemia requiring regular RBC transfusions

Luspatercept, an erythroid maturation agent, is approved for treatment of anaemia in adult patients with β-thalassaemia who require regular red blood cell (RBC) transfusions. The phase 3 BELIEVE study is evaluating the efficacy and safety of this drug. A recent analysis demonstrated that a higher proportion of luspatercept-treated patients shifted to lower serum ferritin, liver iron concentration, and myocardial iron levels during the first 48 weeks compared with placebo-treated patients. This suggests a lower risk of iron overload complications [1].

Regular RBC transfusions are the main supportive treatment for chronic anaemia due to β-thalassaemia. To prevent iron overload from RBC transfusions and associated complications, transfusion-dependent patients require iron chelation therapy. Hence, there is a clinical need to reduce transfusions and iron burden in patients with anaemia due to β-thalassaemia.

Prof. Olivier Hermine (Université de Paris, France) assessed the effect of long-term luspatercept use on iron loading and iron chelation therapy use in the BELIEVE trial (NCT02604433). The 336 participating patients were ≥18 years with β-thalassaemia or haemoglobin (Hb) E/β-thalassaemia (compound β-thalassaemia mutation and/or multiplication of α-globin genes was allowed) and required regular RBC transfusions [2]. Of patients initially randomised to luspatercept, 67.9% were still receiving treatment at the end of 2 years. The vast majority (82.1%) of placebo-treated patients crossed over to luspatercept after study unblinding.

Of 141 luspatercept-treated patients with baseline mean serum ferritin ≥1,000 μg/L, 17.0% of patients achieved post-baseline mean serum ferritin level <1,000 μg/L when assessed over weeks 1-24, compared with 5.0% placebo-treated patients. During week 73-96, 46.4% of luspatercept-treated patients with baseline mean serum ferritin level ≥1,000 μg/L achieved post-baseline mean serum ferritin level <1,000 μg/L. At weeks 24 and 48, 4.2% and 9.7% of luspatercept-treated patients, respectively, shifted from liver iron concentration >3 mg/g dry weight (dw) at baseline to ≤3 mg/g dw, compared with 6.6% and 5.9% of placebo-treated patients. Furthermore, 14.3% of luspatercept patients shifted from liver iron concentration >3 mg/g dw at baseline to ≤3 mg/g dw at week 96. Of luspatercept-treated patients, 20.0% shifted from myocardial iron T2* ≤20 ms at baseline to >20 ms at week 48 compared with 9.1% of placebo-treated patients. At week 96, 25.0% of luspatercept-treated patients shifted from ≤20 ms to >20 ms. Furthermore, patients responding to luspatercept were more likely to achieve clinically meaningful improvements in quality of life compared with placebo [3].

1. Cappellini MD, et al. N Engl J Med. 2020;382:1219-1231.
2. Hermine O, et al. Longitudinal Effect of Luspatercept Treatment on Iron Overload and Iron Chelation Therapy (ICT) in Adult Patients (Pts) with β-Thalassemia in the BELIEVE Trial. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 1697.
3. Cappellini MD, et al. Health-Related Quality of Life Outcomes for Patients with Transfusion-Dependent Beta-Thalassemia Treated with Luspatercept in the BELIEVE Trial. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 364.

Posted on 18 February 202115 February 2024