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 × 109/L subgroup (19/49 [39%] vs. 8/47 [17%]) and with ruxolitinib in the baseline platelets ≥ 200 × 109/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 × 109/L.