Long-Term Efficacy and Safety of Luspatercept for Transfusion-Dependent β-Thalassemia

In 2019, the U.S. FDA approved luspatercept to treat anemia in adults with transfusion-dependent β-thalassemia, including those with hemoglobin E/β-thalassemia, based on the primary analysis of the industry-funded, double-blind, randomized, placebo-controlled BELIEVE trial (NEJM JW Oncol Hematol Mar 26 2020 and N Engl J Med 2020; 382:1219), which showed a significant reduction in transfusion burden with luspatercept at a median follow-up of 64 weeks. Now, the investigators report results from a 5-year, open-label extension phase, with a median luspatercept treatment period of 154 weeks.

The transfusion burden continued to decrease with luspatercept: mean decreases from baseline were 4.8 red blood cell units in weeks 1 to 48, 5.8 units in weeks 49 to 96, 6.2 units in weeks 97 to 144, and 6.4 units in weeks 145 to 192. In the luspatercept group, 77% of patients had at least a 33% reduction in transfusion burden from baseline during any 12-week period, and 52% of patients had a 33% reduction during any 24-week period. Reductions in serum ferritin and liver iron concentrations (LIC) extended beyond 96 weeks among those who continued luspatercept treatment.

The most common grade ≥3 treatment-emergent adverse events (TEAEs) among luspatercept-treated patients were anemia (3%), increased LIC (2%), and bone pain (2%). Serious TEAEs occurred in 23%, with thromboembolic events in all of those with splenectomy. No treatment-related deaths and no new safety signals were reported. Subgroup analyses, including patients with HbE/β-thalassemia, showed consistent efficacy.