The expanding therapeutic landscape of β-thalassaemia.

Abstract

β-thalassaemia is characterised by ineffective erythropoiesis, chronic anaemia, haemolysis, and progressive iron-related and non-iron-related morbidity. Although transfusion, iron chelation, multidisciplinary care, and allogeneic haematopoietic stem-cell transplantation have substantially improved outcomes, major gaps persist in treatment burden, access, safety, adherence, and curative feasibility. Over the past decade, the therapeutic landscape has expanded rapidly, with disease-modifying agents targeting erythroid maturation and red cell metabolism, including luspatercept and mitapivat, now available as options for both transfusion-dependent and non-transfusion-dependent β-thalassaemia. In parallel, gene addition and gene editing therapies, particularly beti-cel and exa-cel, have established proof of curative potential independent of donor availability. However, optimal patient selection, response definitions, long-term outcome assessment, affordability, and equitable global access remain central challenges for wide implementation. In this Series paper, we discuss advances in β-thalassaemia treatment over the past decade, including newly approved and late-stage therapies and their future implications, and highlight remaining research gaps.