Preliminary Safety and Efficacy of Luspatercept Initiated at Maximum Approved Dose in Patients with Transfusion Dependent Anemia Due to Very Low, Low and Intermediate Risk MDS with Ring Sideroblasts: First Results of the Lusplus Trial

作者：Katharina S. Götze, Anna Hecht, A. Kubasch, M. Díez-Campelo, Georg Stüssi, David Valcárcel, Patricia Font López, Elvira Mora Casterá, Blanca Xicoy, T. Bernal del Castillo, Dominik Wolf, Nicola Andina, N. Bonadies, Gregor Stehle, K. Gleixner, K. Metzeler, A. Schröder, D. Schipp, M. Tormo, A. A. Piérola, Aristoteles A. N. Giagounidis, M. Puttrich, U. Platzbecker · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-208432 · 被引用次数：3

Background Luspatercept is a first-in-class erythroid maturation agent approved for patients with lower risk MDS with ring sideroblasts (MDS-RS) and transfusion dependent anemia at a starting dose of 1.0 mg/kg based on the results of the phase III randomized placebo-controlled MEDALIST trial (Fenaux et al, N Engl J Med 2020;382:140-51.). Adjustments of luspatercept to a dose of 1.33 mg/kg and a maximum dose of 1.75 mg/kg were allowed based on response and dose delays were initiated at a Hb level above 11.5 g/dl. 37.9% of patients receiving luspatercept achieved the primary endpoint of at least 8 weeks without a need for RBC transfusion. However, 30% of patients in the luspatercept arm of the MEDALIST trial did not receive the planned maximum dose of 1.75 mg/kg. The rationale of the LusPlus trial is thus to exploit the maximum dose of luspatercept from the first dose per patient to achieve an overall increase in response and demonstrate an acceptable safety profile of this dosing regimen. Methods The LusPlus trial is a phase IIIb, open-label, single arm study evaluating the efficacy and safety of luspatercept initiated at a maximum dose of 1.75 mg/kg in transfusion dependent patients with lower-risk MDS and ring-sideroblastic phenotype who are refractory, intolerant, or ineligible to prior erythropoiesis-stimulating agent (ESA) treatment. Patients receive luspatercept at a starting dose of 1.75 mg/kg on day 1 of each 21-day cycle for 24 weeks. The Hb threshold for administr...