Luspatercept for Non–Transfusion-Dependent β-Thalassemia

In patients with transfusion-dependent β-thalassemia, luspatercept is used to enhance late stages of erythropoiesis and reduce transfusion burden. Patients with non–transfusion-dependent β-thalassemia have less-severe anemia than do those with transfusion-dependent disease, but they have limited treatment options beyond as-needed transfusion, despite compromises in morbidity, mortality, and quality of life.

Now, investigators have conducted a multicenter, randomized, placebo-controlled, phase 2 study to test the efficacy and safety of luspatercept in 145 patients with non–transfusion-dependent β-thalassemia (median age, 40 years; 57% female; median baseline hemoglobin, 8.2 g/dL). The primary endpoint was the proportion of patients with a mean hemoglobin increase of 1 g/dL in the absence of transfusion during weeks 13 through 24.

Key findings included the following:

• The study met its primary endpoint; 77% of patients in the luspatercept group achieved a mean hemoglobin increase of ≥1.0 g/dL compared with 0% of patients in the placebo group.
• The key secondary endpoint — patient-reported improvement in tiredness/weakness from baseline — was not met.
• The most common adverse events included bone pain (37%), headache (30%), arthralgia (29%), back pain (28%), prehypertension (23%), and hypertension (20%).