A clinical study on the Efficacy and safety of luspatercept in Chinese patients with non-transfusion-dependent β-thalassemia

Abstract

Abstract Background: β-thalassemia is a hereditary anemia caused by insufficient hemoglobin production due to reduced or complete absence of β-globin chains synthesis. Non-transfusion-dependent (NTD) β-thalassemia refers to forms that do not require lifelong regular red blood cell (RBC) transfusions for survival. Though patients usually need occasional or frequent RBC transfusions only during specific periods, they nevertheless experience over their lifetime chronic anemia and iron overload that can lead to a series of complications. The BEYOND study showed that luspatercept sustainably increases hemoglobin levels while improving quality of life in patients with NTD β-thalassemia but there is a lack of data in Chinese patients. This study aimed to investigate the efficacy and safety of luspatercept in the treatment of Chinese patients with NTD β-thalassemia, so as to provide evidence and reference for future clinical use. Methods: This was a prospective, single-arm, multicenter, open-label study, which planned to enroll 70 β-thalassemia patients aged ≥ 18 years with RBC transfusion of ≤ 7.5 U and a hemoglobin level of ≤ 90 g/L within 24 weeks prior to enrollment. Patients with concomitant α-thalassemia were allowed for inclusion. Participants received subcutaneous luspatercept 1.0 mg/kg Q3W, with the main observation period being 24 weeks. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Results: From September 2023 to July 2025, 50 patients were enrolled, including 48 (96%) with β-thalassemia alone and 2 (4%) with β/α-thalassemia. The participants had a mean age of 47.4 years (range: 22–77), with a mean hemoglobin level of 7.3 g/dL (range: 4.7–9.3), a mean transfusion burden of 0.47 U/24 weeks (range: 0–6 U/24 weeks), and a mean serum ferritin level of 1242.6 ng/mL (range: 4.29–2804). As of July 28, 2025, 21 patients completed the 24-week observation for the primary endpoint, and the mean hemoglobin level was 9.4 g/dL (range: 7.1–12.2), representing an increase of 2.1 g/dL (+ 29%) from baseline. Among these patients, 14 (67%) had a hemoglobin increase ≥ 1.0 g/dL, the number of patients requiring blood transfusion decreased by 1 (-100%), and the transfusion burden over 24 weeks decreased by 4 U. At 6 weeks of treatment, the mean hemoglobin level in 47 patients increased by 1.3 g/dL (+ 18%), with 29 (62%) patients achieving hemoglobin increase ≥ 1.0 g/dL. 14 patients completed the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue assessments, showing decreased fatigue scores at week 24 compared to baseline (mean score: 12.07 vs 20). The adverse event profile was similar to the commonly reported adverse reactions of luspatercept, and no adverse events of grade 3 or higher were observed. The patient with the longest duration of treatment received 22 doses (over 66 weeks) and showed good tolerance. Conclusion: Luspatercept is an effective and well-tolerated treatment option for Chinese adult patients with NTD β-thalassemia. Further studies with an expanded sample size and extended follow-up duration are needed to observe its effects on serum ferritin and spleen thickness.