Luspatercept Improves Symptoms in Nontransfusion Dependent β-Thalassemia

Luspatercept (REBLOZYL; Celgene) improved nontransfusion-dependent β-thalassemia (NTDT)-related patient-reported (PRO) symptoms in patients enrolled in the BEYOND study (NCT03342404).¹

Data from a new analysis of BEYOND were presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, held December 9-12, in San Diego, California, by Kevin H.M. Kuo, MD, FRCPC, MSc, adult hematologist and clinician-investigator in the Red Blood Cell Program, University of Toronto.

"Patients with NTDT suffer from chronic anemia due to ineffective erythropoiesis. The phase 2, randomized, placebo-controlled BEYOND study demonstrated that luspatercept increased hemoglobin (Hb), reduced transfusion burden, and improved NTDT-related symptoms based on the data with 48 weeks of follow-up2,” Kuo and coauthors wrote in their abstract.¹

Kuo and colleagues analyzed data from 144patients with NTDT randomized 2:1 to luspatercept with best supportive care compared with placebo with best supportive care through 96 weeks of follow-up (95 lustarcept; 49 placebo). Best supportive care included red blood cell (RBC) transfusions and iron chelation therapy as deemed necessary by investigators. PRO symptoms were assessed by the NTDT Patient Reported Outcome (NTDT-PRO) and Patient Global Impression of Severity (PGI-S) in a daily electronic diary starting 7 days prior to the first dosing day until Week 24, and thereafter over the 7 days prior to dosing at every other dosing visit. The Patient Global Impression of Change (PGI-C) was administered at every other dosing visit, starting with the first dosing day. The NTDT-PRO measures 2 NTDT anemia-related symptom domains, Tiredness/Weakness (T/W) and Shortness of Breath (SoB).

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The investigators found that least squares mean changes from baseline in the lustapatercept arm consistently had greater improvements on T/W and SoB domains than the placebo arm, which were more pronounced starting at week 24 and sustained through week 96.LS mean changes differences from baseline ranged from -0.89 to -0.21 in the T/W domain and from -0.80 to -0.45 in the SoB domain. Between-treatment differences were significant (P <.05) at week 30, week 36, and week 72 in the T/W domain and at weeks 30, 48, and 72 in the SoB domain. LS mean changes from baseline in overall symptoms also showed improvement in the luspatercept arm, as assessed by PGI-S, while patients in the placebo arm tended to worsen over time. The between-treatment difference was statistically significant (P <.05) across most time periods. Most patients in the luspatercept arm reported scores overall symptoms were “a little better” or more on PGI-C at weeks 72 (89%) and 96 (87%) compared with most patients in the placebo arm that reported no change at weeks 72 (61%) and 96 (75%).

“Analysis of the PRO data collected in BEYOND suggests that, in addition to improvements in Hb, patients with NTDT treated with luspatercept experienced durable improvement in NTDT-related symptoms, from a patient perspective, through at least 96 weeks of treatment,” Kuo and colleagues concluded.

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REFERENCES
1. Musallam KM, Taher AT, Kattamis A, et al. Durable symptom improvement for patients with non-transfusion dependent thalassemia treated with luspatercept: Patient-reported outcomes from the BEYOND study. Presented at: ASH 2023 Annual Meeting & Exposition. December 9-12; San Diego, CA. Abstract #2474
2. Taher AT, Cappellini MD, Kattamis A, et al. Luspatercept for the treatment of anaemia in non-transfusion-dependent β-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial. Lancet Haematol; 2022. 9(10): E733-E744. doi: 10.1016/S2352-3026(22)00208-3