β-thalassemia is a hereditary blood disorder characterised by impaired haemoglobin (Hb) production and chronic anaemia of varying severity1. Patients with transfusion-dependent β-thalassemia require lifelong regular red blood cell transfusions for survival as well as iron chelation therapy to manage iron overload2. However, many patients still experience multiple morbidities due to iron toxicity. There is also a need for treatments that lessen the burden of transfusions. Luspatercept is a recombinant fusion protein that enhances late-stage erythropoiesis and improves haemoglobin levels in patients with β-thalassemia3.
Recently, the primary analysis of the phase 3 BELIEVE trial (NCT02604433) showed an improved reduction of the need for red blood cell transfusion in patients receiving luspatercept over placebo through 24 weeks (21.3% versus 4.5%)4. However, long-term results of luspatercept were unknown. Prof. Maria Capellini (University of Milan, Italy) now presented long-term results of the BELIEVE study, including the effects of treatment on the transfusion burden and liver iron concentration5.
A total of 336 transfusion-dependent β-thalassemia patients were enrolled and randomised 2:1 to luspatercept or placebo. After 24 weeks of treatment, the study was unblinded and patients in the placebo arm were allowed to cross over to luspatercept. Post-treatment follow-up was 192 weeks post-last dose. Data presented was from 224 participants who were allocated to luspatercept from the start of the study. Of these, 211 completed 24 weeks of treatment, 202 completed 48 weeks, 155 completed 96 weeks, 125 completed 144 weeks, and 6 participants (so far) completed 192 weeks. Discontinuation was partly due to the commercial availability of luspatercept. Data were presented from 3 different study data cuts with a median of 64 weeks, 95 weeks, and 154 weeks of treatment, respectively.
The percentage of patients with a reduction of ≥33% transfusion burden in any rolling 12-week period increased in time, from 70.5% to 77.2%. The percentage of patients with a reduction of transfusion burden of ≥50% also increased in time, from 40.2% to 50.0%. In addition, the median duration of the reduction of transfusion burden increased, whereas the number of units of red blood cells per transfusion decreased. The percentage of patients achieving transfusion independence increased from 10.7% to 12.1%. Finally, at week 144, a small decrease was observed in the liver iron concentration of patients treated with luspatercept.
“Continued treatment with luspatercept, up to 3 years, allowed more patients to experience a reduction in red blood cell transfusion burden and an increase in time between transfusions,” summarised Dr Cappelini.