Photo Credit: istyock

The following is a summary of “Long-term efficacy and safety of luspatercept for the treatment of anaemia in patients with transfusion-dependent β-thalassaemia (BELIEVE): final results from a phase 3 randomised trial,” published in the March 2025 issue of Lancet Haematology by Cappellini et al. 

Treatment options for reducing red blood cell (RBC) transfusion burden in transfusion-dependent β-thalassaemia are limited. 

Researchers conducted a retrospective study on long-term data from the phase 3 BELIEVE trial of luspatercept in transfusion-dependent β-thalassaemia.  

They conducted a phase 3, randomized, double-blind, placebo-controlled study at 65 sites in 15 countries. They included adults with transfusion-dependent β-thalassaemia or hemoglobin E/β-thalassaemia and an Eastern Cooperative Oncology Group score of 0–1. Patients were randomly assigned (2:1) to luspatercept (1·0–1·25 mg/kg) or placebo every 21 days. After unblinding, patients could receive luspatercept in the open-label extension phase. They analyzed the updated primary endpoint and reported long-term efficacy (intention-to-treat) and safety (safety population) over ~3 years. 

The results showed that 336 patients were randomized to luspatercept (n=224) or placebo (n=112), with a median age of 30 years (IQR 23–40); 195 (58%) were female and 141 (42%) males. As of Jan 5, 2021, the median treatment duration for luspatercept was 153.6 weeks (IQR 81.0–171.0), and follow-up was 163.1 weeks (140.5–176.2). No comparative analyses were performed after week 96. Luspatercept reduced RBC transfusion burden, with mean decreases of 6.2 RBC units (SD 5.7) at weeks 97–144 and 6.4 (4.3) at weeks 145–192. A 33% or greater reduction occurred in 173 (77%) patients over any 12-week interval and 116 (52%) over any 24-week interval. The median duration of this response was 586.0 days (IQR 264.0–1010.0). Among 315 luspatercept-treated patients (including 92 who crossed over), grade 3 or worse treatment-emergent adverse events (TEAEs) included anaemia (9 [3%]), increased liver iron (7 [2%]), and bone pain (7 [2%]); serious TEAEs occurred in 71 (23%) patients. No treatment-related deaths occurred. 

Investigators affirmed luspatercept’s long-term efficacy in reducing transfusion burden in transfusion-dependent β-thalassaemia with a manageable safety profile. 

Source: thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00376-4/abstract