TY - JOUR
T1 - Simplify-1
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
N1 - Publisher Copyright:
Copyright © 2017 American Society of Clinical Oncology. All rights reserved.
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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U2 - 10.1200/JCO.2017.73.4418
DO - 10.1200/JCO.2017.73.4418
M3 - Article
C2 - 28930494
AN - SCOPUS:85035815718
SN - 0732-183X
VL - 35
SP - 3844
EP - 3850
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 34
ER -