Profile of Luspatercept in the Treatment of Anemia in Adults with Non-Transfusion-Dependent β-Thalassemia (NTDT): Design, Development and Potential Place in Therapy

Khaled M Musallam,1 Ali T Taher,2 Antonis Kattamis,3 Kevin HM Kuo,4 Sujit Sheth,5 Maria Domenica Cappellini6 1Thalassemia Center, Burjeel Medical City, Abu Dhabi, United Arab Emirates; 2Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon; 3First Department of Pediatrics, National and Kapodistrian University of Athens, Athens, Greece; 4Division of Hematology, University of Toronto, Toronto, ON, Canada; 5Division of Hematology and Oncology, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA; 6Department of Clinical Sciences and Community, University of Milan, Ca’ Granda Foundation IRCCS Maggiore Policlinico Hospital, Milan, ItalyCorrespondence: Maria Domenica Cappellini, Department of Clinical Sciences and Community, University of Milan, Ca’ Granda Foundation IRCCS Maggiore Policlinico Hospital, Milan, 20122, Italy, Tel + 39 02 5503 3752, Email maria.cappellini@unimit.itAbstract: Over the past decade, evidence has been mounting on the detrimental clinical sequelae of untreated anemia in patients with non-transfusion-dependent β-thalassemia (NTDT). There are no pharmacologic agents that are specifically approved for the management of anemia in NTDT, and available options such as splenectomy, transfusion therapy, and hydroxyurea each come with their own shortcomings, especially for long-term use. Luspatercept is an erythroid maturation agent that has been evaluated in a Phase 2, randomized trial and showed a significant benefit in raising hemoglobin level by at least 1 g/dL in adults with NTDT and a baseline hemoglobin level ≤ 10 g/dL. These data led to luspatercept’s approval by the European Commission for the treatment of anemia in adults with NTDT and presents the first evidence-based approach for a novel agent that is able to ameliorate anemia in this patient population.Keywords: anemia, ineffective erythropoiesis, iron, management, thalassemia, transfusion