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

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Janus Kinases
Primary Myelofibrosis
Janus Kinase 1
Janus Kinase 2
Spleen
INCB018424
N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
Therapeutics
Peripheral Nervous System Diseases
Thrombocytopenia
Anemia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Simplify-1 : A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis. / Mesa, Ruben A.; Kiladjian, Jean Jacques; Catalano, John V.; Devos, Timothy; Egyed, Miklos; Hellmann, Andrzei; McLornan, Donal; Shimoda, Kazuya; Winton, Elliott F.; Deng, Wei; Dubowy, Ronald L.; Maltzman, Julia D.; Cervantes, Francisco; Gotlib, Jason.

In: Journal of Clinical Oncology, Vol. 35, No. 34, 01.12.2017, p. 3844-3850.

Research output: Contribution to journalArticle

Mesa, RA, Kiladjian, JJ, Catalano, JV, Devos, T, Egyed, M, Hellmann, A, McLornan, D, Shimoda, K, Winton, EF, Deng, W, Dubowy, RL, Maltzman, JD, 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, vol. 35, no. 34, pp. 3844-3850. https://doi.org/10.1200/JCO.2017.73.4418
Mesa, Ruben A. ; Kiladjian, Jean Jacques ; Catalano, John V. ; Devos, Timothy ; Egyed, Miklos ; Hellmann, Andrzei ; McLornan, Donal ; Shimoda, Kazuya ; Winton, Elliott F. ; Deng, Wei ; Dubowy, Ronald L. ; Maltzman, Julia D. ; Cervantes, Francisco ; Gotlib, Jason. / Simplify-1 : A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 34. pp. 3844-3850.
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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-na{\"i}ve 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-na{\"i}ve 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.",
author = "Mesa, {Ruben A.} and Kiladjian, {Jean Jacques} and Catalano, {John V.} and Timothy Devos and Miklos Egyed and Andrzei Hellmann and Donal McLornan and Kazuya Shimoda and Winton, {Elliott F.} and Wei Deng and Dubowy, {Ronald L.} and Maltzman, {Julia D.} and Francisco Cervantes and Jason Gotlib",
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T2 - A phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor–naïve patients with myelofibrosis

AU - Mesa, Ruben A.

AU - Kiladjian, Jean Jacques

AU - Catalano, John V.

AU - Devos, Timothy

AU - Egyed, Miklos

AU - Hellmann, Andrzei

AU - McLornan, Donal

AU - Shimoda, Kazuya

AU - Winton, Elliott F.

AU - Deng, Wei

AU - Dubowy, Ronald L.

AU - Maltzman, Julia D.

AU - Cervantes, Francisco

AU - Gotlib, Jason

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

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