Phase III INDEPENDENCE trial: Luspatercept in MF-associated anemia

Results from the randomized, double-blind, phase III INDEPENDENCE trial (NCT04717414) evaluating luspatercept vs placebo in patients with myelofibrosis (MF)-associated anemia receiving concomitant Janus kinase inhibitor (JAKi) therapy were presented by Francesco Passamonti at the European Hematology Association (EHA) 2026 Congress, June 11–14, 2026, Stockholm, SE. Patients (N = 313) were randomized 2:1 to luspatercept + best supportive care (n = 208) or placebo (n = 105). The primary endpoint was red blood cell transfusion independence (RBC-TI) for ≥12 consecutive weeks starting within the first 24 weeks (RBC-TI ≥12).    

Key data: In the luspatercept group, 23.1% of patients achieved RBC-TI ≥12 weeks vs 13.3% in the placebo group (p = 0.0674); this did not meet the pre-specified threshold of p < 0.044. A post hoc sensitivity analysis demonstrated a nominally significant improvement in RBC-TI with luspatercept compared with placebo (p = 0.0398). Luspatercept demonstrated consistent benefit across secondary endpoints, including RBC-TI ≥16 weeks (19.2% vs 11.4%) and ≥50% reduction in transfusion burden (TB) with ≥4 RBC units (40.9% vs 22.9%). The safety profile was manageable and consistent with the advanced MF disease setting. 

Key learning: Although the INDEPENDENCE trial did not meet its primary endpoint, luspatercept demonstrated clinically meaningful improvements in RBC-TI, TB reduction, and hemoglobin levels in patients with MF-associated anemia receiving JAKi therapy, supporting its potential as a treatment option in this setting.