SIMPLIFY-1 and MOMENTUM trials: Impact of Hb improvement on OS with momelotinib

During the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, Pankit Vachhani presented findings from a post hoc analysis of the phase III SIMPLIFY-1 (NCT01969838) and MOMENTUM (NCT04173494) trials, evaluating the impact of hemoglobin improvement with momelotinib on overall survival (OS). Patients with myelofibrosis (MF) with baseline hemoglobin (Hb) <10 g/dL from the momelotinib arms of each trial were included (SIMPLIFY-1, n = 86; MOMENTUM, n = 126).

Key data: In SIMPLIFY-1 and MOMENTUM, 27% and 19% of patients achieved Hb ≥10 g/dL at Week 24, respectively. In SIMPLIFY-1 (Janus kinase inhibitor [JAKi] naïve), median OS was 56.7 months in patients who achieved this threshold vs 39.9 months in those who did not (hazard ratio [HR], 0.58). In MOMENTUM (JAKi experienced), median OS was not reached in those who achieved the Hb threshold vs 38.7 months in those who did not (HR, 0.59). 

Key learning: In patients with baseline moderate–severe anemia, achievement of Hb ≥10 g/dL at Week 24 with momelotinib was associated with numerically longer OS, regardless of JAKi exposure. Earlier intervention with momelotinib in the MF disease course may contribute to better outcomes.