Simplify-1: A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis

Ruben A. Mesa, Jean Jacques Kiladjian, 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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3844-3850
Number of pages7
JournalJournal of Clinical Oncology
Volume35
Issue number34
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mesa, R. A., Kiladjian, J. J., Catalano, J. V., Devos, T., Egyed, M., Hellmann, A., McLornan, D., Shimoda, K., Winton, E. F., Deng, W., Dubowy, R. L., Maltzman, J. D., Cervantes, F., & Gotlib, J. (2017). Simplify-1: A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis. Journal of Clinical Oncology, 35(34), 3844-3850. https://doi.org/10.1200/JCO.2017.73.4418