β-thalassemia is an inherited hemoglobinopathy with faulty β-globin chain production, leading to ineffective erythropoiesis and transfusion dependence in severe forms. Transfusion-dependent β-thalassemia (TDT) has been linked to iron overload, decreased quality of life, and long-term consequences despite supportive care such as iron chelation. Luspatercept, a recombinant fusion protein that acts on the TGF-β superfamily signaling pathway, has appeared as a new therapeutic intervention to decrease the transfusion burden by inducing late-stage erythroid maturation. Clinical trials, such as Phase I to III trials and the BELIEVE trial, have confirmed that luspatercept effectively reduces the transfusion burden and enhances health-related quality of life in TDT patients. Nevertheless, possible side effects like bone pain, thromboembolic events, and extramedullary hematopoiesis should be taken into account carefully. The therapy is also contraindicated among patients who have active EMH masses, and its safety during pregnancy has yet to be confirmed. Luspatercept also has the potential to treat other blood disorders such as MDS-RS. This Informative Letter emphasizes the changing role of luspatercept as a disease-modifying therapy in the management of β-thalassemia.
Advani et al. (Mon,) studied this question.