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Abstract：
Bone marrow fibrosis (BMF) is a pathological feature of myelofibrosis, with higher grades associated with poor prognosis. Limited data exist on the association between outcomes and BMF changes. We present BMF data from Janus kinase (JAK) inhibitor-naive patients from SIMPLIFY-1 (NCT01969838), a double-blind, randomized, phase 3 study of momelotinib vs ruxolitinib. Baseline and week 24 bone marrow biopsies were graded from 0 to 3 as per World Health Organization criteria. Other assessments included Total Symptom Score, spleen volume, transfusion independence status, and hemoglobin levels. Paired samples were available from 144 and 160 patients randomized to momelotinib and ruxolitinib. With momelotinib and ruxolitinib, transfusion independence was achieved by 87% and 44% of patients with BMF improvement of ≥1 grade and 76% and 56% of those with stable/worsening BMF; there was no association between BMF changes and transfusion independence for either arm (momelotinib, p = .350; ruxolitinib, p = .096). Regardless of BMF changes, hemoglobin levels also generally increased on momelotinib but decreased on ruxolitinib. In addition, no associations between BMF changes and spleen (momelotinib, p = .126; ruxolitinib, p = .407)/symptom (momelotinib, p = .617; ruxolitinib, p = .833) outcomes were noted, and no improvement in overall survival was observed with ≥1-grade BMF improvement (momelotinib, p = .395; ruxolitinib, p = .407). These data suggest that the anemia benefit of momelotinib is not linked to BMF changes, and question the use of BMF assessment as a surrogate marker for clinical benefit with JAK inhibitors.
摘要：
骨髓纤维化（BMF）是骨髓纤维化的病理特征，较高的评分与不良预后相关。关于结果与BMF变化之间的关联的数据有限。我们提供了来自SIMPLIFY-1（NCT01969838）的Janus激酶（JAK）抑制剂初治患者的BMF数据，双盲，随机化，莫美罗替尼与鲁索替尼的3期研究。根据世界卫生组织标准，基线和第24周骨髓活检从0到3进行分级。其他评估包括总症状评分，脾脏体积,输血独立状态，和血红蛋白水平。成对的样本来自随机分配到莫美罗替尼和鲁索替尼的144和160名患者。莫美罗替尼和鲁索替尼，BMF改善≥1级的患者分别有87％和44％，BMF稳定/恶化的患者分别有76％和56％实现了输血独立性；任何一个手臂的BMF变化与输血独立性之间都没有关联（莫美罗替尼，p=.350；鲁索利替尼，p=.096）。不管BMF有什么变化，莫美罗替尼组的血红蛋白水平通常也升高,但鲁索替尼组的血红蛋白水平降低.此外,BMF变化和脾脏之间没有关联(莫美罗替尼，p=.126；鲁索利替尼，p=.407)/症状(莫美罗替尼，p=.617；鲁索利替尼，p=.833)注意到结果，在BMF改善≥1级的情况下，总生存率没有改善(莫美罗替尼，p=.395；鲁索利替尼，p=.407）。这些数据表明，莫美罗替尼的贫血益处与BMF变化无关，并质疑使用BMF评估作为JAK抑制剂临床获益的替代指标。
