Spleen Volume Reduction and Transfusion Independence With Momelotinib Versus Ruxolitinib and Associated Overall Survival With Momelotinib in JAK Inhibitor–Naive Patients With Myelofibrosis and Anemia: Subgroup Analyses of SIMPLIFY-1

Introduction Improvements in splenomegaly, anemia, and overall survival (OS) are key considerations in the management of patients with myelofibrosis. In the phase III SIMPLIFY-1 trial (NCT01969838), momelotinib was noninferior to ruxolitinib for spleen volume reduction ≥ 35% (SVR35) and nominally superior for transfusion independence (TI) at week 24 in Janus kinase (JAK) inhibitor–naive patients. However, the relative impact of these endpoints on OS in anemic patients has not been described. Materials and Methods The present post hoc analysis evaluated week 24 SVR35, TI, and dual responses (SVR35 + TI) in patients with baseline hemoglobin < 10 g/dL. Results SVR35 rates were similar overall with momelotinib versus ruxolitinib (27/86 [31%] vs. 31/94 [33%]), but higher with momelotinib in the baseline platelets < 200 × 10 9 /L subgroup (19/49 [39%] vs. 8/47 [17%]) and with ruxolitinib in the baseline platelets ≥ 200 × 10 9 /L subgroup (8/37 [22%] vs. 23/47 [49%]). Week 24 SVR35 + TI was also more common with momelotinib (23/86 [27%]) than with ruxolitinib (7/94 [7%]). Subsequent OS analysis focused on the momelotinib arm only, as the crossover trial design precluded analysis of long-term OS with ruxolitinib. OS was longer in patients who were transfusion independent and/or achieved SVR35 at week 24 versus those who met neither endpoint (TI alone: n = 17, hazard ratio [HR], 0.25 [95% CI, 0.09-0.70]; SVR35 + TI: n = 23, HR, 0.40 [95% CI, 0.18-0.87]). Conclusion These results highlight that both spleen- and anemia-related benefits of momelotinib correlate with improved OS, supporting prioritization of TI in anemic patients for optimal long-term outcomes, and suggest that momelotinib may be the preferred JAK inhibitor in anemic patients with platelets < 200 × 10 9 /L.