Dual transfusion independence and spleen volume reduction are associated with overall survival in patients with myelofibrosis treated with momelotinib: post hoc analyses of SIMPLIFY-1 and MOMENTUM

Abstract Spleen volume reduction (SVR) and transfusion independence (TI) are associated with improved overall survival (OS) in myelofibrosis, but the joint contribution of these endpoints remains unclear. These post hoc analyses evaluated the association between concurrent SVR and TI at week 24 with OS in patients with primary or post–polycythemia vera/essential thrombocythemia myelofibrosis treated with momelotinib in the phase 3 SIMPLIFY‑1 (JAK inhibitor–naive) and MOMENTUM (JAK inhibitor–experienced) trials. Dual response was defined as joint TI and SVR thresholds of ≥ 35%, ≥ 25%, ≥ 15%, or ≥ 10% from baseline at week 24. Dual SVR + TI responders consistently demonstrated numerically longer OS vs. nonresponders across SVR thresholds. In SIMPLIFY‑1, hazard ratios (HRs) for death ranged from 0.26 (SVR10 + TI, 95% CI 0.16–0.43) to 0.64 (SVR35 + TI, 95% CI 0.38–1.10), with median OS exceeding that of nonresponders (e.g., 120.8 vs. 41.5 months for SVR10 + TI). In MOMENTUM, dual responders similarly showed numerically improved OS, with HRs of 0.33 (SVR10 + TI, 95% CI 0.17–0.65) and 0.32 (SVR35 + TI, 95% CI 0.11–0.88), with median OS not reached in responders (for both SVR10 + TI and SVR35 + TI) vs. 28.7 (nonresponders of SVR10 + TI) or 32.0 months (nonresponders of SVR35 + TI). Patients with both TI and SVR at week 24 demonstrated longer OS across all SVR thresholds evaluated, with the most pronounced separation of survival curves observed at the lowest SVR thresholds (≥ 10% and ≥ 15%). This pattern supports the concept that, in patients treated with momelotinib who achieve or maintain TI, relatively modest SVRs may be sufficient to achieve a survival advantage.