Impact of SF3B1 mutation on luspatercept efficacy in anemic MPN or MDS/MPN

A single-center observational study investigated SF3B1 mutation status as a predictive biomarker for the efficacy of luspatercept for the treatment of patients with anemic myeloproliferative neoplasms (MPN; n = 18) or myelodysplastic syndrome (MDS)/MPN (n = 7). The primary endpoint was overall response rate (ORR), defined as red blood cell transfusion independence and hemoglobin improvement. Cui et al. published the results in Annals of Hematology.  

Key data: At a median follow-up of 6 months, the ORR in the overall cohort was 48%. ORR rates were higher in patients with SF3B1 mutations (n = 6) compared with patients with SF3B1 wild-type (n = 19) (83.3%; 95% confidence interval [CI], 52.1–97.6 vs 36.8%; 95% CI, 21.7–54.9; p = 0.012). The ORR for the MDS/MPN subgroup was 57.1%; response rates were 75% in patients with SF3B1 mutation (n = 4) vs 33.3% in patients with wild-type SF3B1 (n = 3; p = 0.035). In the MPN subgroup, the ORR was 44.4%; response rates were 100% in patients with SF3B1 mutations (n = 2) vs 37.5% in patients with wild-type SF3B1 (n = 16; p = 0.042). There was one treatment discontinuation due to Grade 2 rash. No Grade ≥4 adverse events (AEs) were observed.  

Key learning: SF3B1 mutation was significantly associated with improved response to luspatercept across both MPN and MDS/MPN patient populations with anemia, supporting its role as a therapeutic biomarker for patient selection.