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J Clin Oncol. 2017 Dec 1;35(34):3844-3850. doi: 10.1200/JCO.2017.73.4418. Epub 2017 Sep 20.

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

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Ruben A. Mesa, Mayo Clinic Cancer Center, Scottsdale, AZ; Jean-Jacques Kiladjian, Saint-Louis Hospital (Assistance Publique-Hôpitaux de Paris) and Paris Diderot University, Paris, France; John V. Catalano, Frankston Hospital and Monash University, Melbourne, Victoria, Australia; Timothy Devos, University Hospital Leuven and Katholieke Universiteit Leuven, Leuven, Belgium; Miklos Egyed, Kaposi Mor Teaching Hospital, Kaposvar, Hungary; Andrzei Hellmann, Medical University of Gdańsk, Gdańsk, Poland; Donal McLornan, Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom; Kazuya Shimoda, University of Miyazaki, Miyazaki, Japan; Elliott F. Winton, Emory University School of Medicine, Atlanta, GA; Wei Deng, Ronald L. Dubowy, and Julia D. Maltzman, Gilead Sciences, Foster City; Jason Gotlib, Stanford Cancer Institute, Stanford, CA; and Francisco Cervantes, Hospital Clinic, Institut D'Investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain.


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

[Indexed for MEDLINE]

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