SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor–Naïve Patients With Myelofibrosis

• DOI: 10.1200/jco.2017.73.4418
• Publication Date: 2017-09-20T19:59:13Z
• Authors: Ruben A. Mesa; Jean-Jacques Kila...; John V. Catalano; Timothy Devos; Miklos Egyed; Andrzei Hellmann; Donal McLornan; Kazuya Shimoda; Elliott F. Winton; Wei Deng; Ronald L. Dubowy; Julia D. Maltzman; Francisco Cervantes; Jason Gotlib
• Keywords: Ruxolitinib; Janus kinase inhibitor; Clinical endpoint

Purpose We evaluated the efficacy and safety of momelotinib, a potent selective Janus kinase 1 2 inhibitor (JAKi), compared with ruxolitinib, in JAKi-naïve patients myelofibrosis. Patients Methods (N = 432) high risk or intermediate-2 symptomatic intermediate-1 myelofibrosis were randomly assigned to receive 24 weeks treatment momelotinib 200 mg once daily ruxolitinib 20 twice day (or per label), after which all could open-label momelotinib. The primary end point was ≥ 35% reduction spleen volume at therapy. Secondary points rates symptom response effects on RBC transfusion requirements. Results A week achieved by similar proportion both arms: 26.5% group 29% (noninferior; P .011). 50% total score observed 28.4% 42.2% who received respectively, indicating that noninferiority not met ( .98). Transfusion rate, independence, dependence improved (all nominal ≤ .019). most common grade 3 hematologic abnormalities either thrombocytopenia anemia. Grade infections occurred 7% 3% ruxolitinib. Treatment-emergent peripheral neuropathy 10% 2) 5% 3). Conclusion In myelofibrosis, noninferior for but response. Momelotinib associated reduced requirement.