SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor-Naive Patients With Myelofibrosis
SIMPLIFY-1: A Phase III Randomized Trial of Momelotinib Versus Ruxolitinib in Janus Kinase Inhibitor-Naive Patients With Myelofibrosis
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DOI：
10.1200/jco.2017.73.4418
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发表时间：
2017-12-01
影响因子：
45.3
通讯作者：
Gotlib, Jason
中科院分区：
文献类型：
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作者：
Mesa, Ruben A.;Kiladjian, Jean-Jacques;Gotlib, Jason
目的：我们评价了momelotinib（一种有效的选择性Janus激酶1和2抑制剂（JAKi））与ruxolitinib相比的疗效和安全性，患者和方法患有高风险或中等-2风险或症状性中等-2风险的患者（N = 432），1例骨髓纤维化风险患者随机分配接受24周momelotinib 200 mg每日1次或ruxolitinib 20 mg每日2次治疗（或根据标签），之后所有患者均可接受开放标签的momelotinib。主要终点是治疗24周时脾脏体积减少≥ 35%。次要终点是症状反应率和对RBC输血需求的影响。结果两个治疗组中相似比例的患者在第24周脾脏体积减少≥ 35%：momelotinib组为26.5%，ruxolitinib组为29%（非劣效性; P = 0.011）。在接受momelotinib和ruxolitinib的患者中，分别有28.4%和42.2%的患者观察到总症状评分降低>= 50%，表明不符合非劣效性（P = 0.98）。接受momelotinib治疗后，输血率、输血独立性和输血依赖性均得到改善（两组中所有标称P = 3的血液学异常均为血小板减少症和贫血。7%接受momelotinib治疗的患者和3%接受ruxolitinib治疗的患者发生≥ 3级感染。10%接受momelotinib治疗的患者发生治疗后出现的周围神经病变（所有级别
PurposeWe evaluated the efficacy and safety of momelotinib, a potent and selective Janus kinase 1 and 2 inhibitor (JAKi), compared with ruxolitinib, in JAKi-naive patients with myelofibrosis.Patients and MethodsPatients (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.ResultsA >= 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 = 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