Impact of Hemoglobin Improvement on Survival in Patients With Myelofibrosis and Anemia Treated With Momelotinib in the SIMPLIFY ‐1 and MOMENTUM Trials

OBJECTIVES: These post hoc analyses of 2 phase 3 myelofibrosis trials assessed the kinetics and prognostic value of achieving hemoglobin ≥ 10 g/dL with momelotinib. METHODS: Median (range) time to hemoglobin ≥ 10 g/dL was assessed in momelotinib-randomized patients with baseline hemoglobin < 10 g/dL in the SIMPLIFY-1 (JAK inhibitor naive) and MOMENTUM (JAK inhibitor experienced) trials. Survival from treatment initiation was evaluated via Kaplan-Meier curves and Cox models. RESULTS: In SIMPLIFY-1, 54/86 patients (63%) achieved hemoglobin ≥ 10 g/dL by week 24: moderate anemia, 40/58 (69%), 0.6 (0.4-5.1) months; severe anemia, 14/28 (50%), 1.4 (0.5-4.7) months. In MOMENTUM, 45/126 patients (36%) achieved hemoglobin ≥ 10 g/dL by week 24: moderate anemia, 30/64 (47%), 0.5 (0.3-4.6) months; severe anemia, 15/62 (24%), 0.5 (0.5-5.6) months. Achieving hemoglobin ≥ 10 g/dL by week 24 was numerically associated with longer survival: SIMPLIFY-1 HR, 0.53 (95% CI, 0.27-1.05); MOMENTUM HR, 0.62 (95% CI, 0.33-1.15). In multivariate analysis, only week 24 transfusion independence was associated with survival. CONCLUSIONS: Achievement of hemoglobin ≥ 10 g/dL may be a clinically meaningful target in momelotinib-treated patients with myelofibrosis and anemia. Those without JAK inhibitor experience and/or with moderate anemia were more likely and faster to achieve this threshold, supporting earlier momelotinib initiation to optimize outcomes. TRIAL REGISTRATION: CLINICALTRIALS. GOV IDENTIFIER: NCT01969838, NCT04173494.