文章：

Momelotinib治疗骨髓纤维化的7年随访

Momelotinib therapy for myelofibrosis: a 7-year follow-up

原文发布日期：2018-03-07

DOI: 10.1038/s41408-018-0067-6

类型: Article

开放获取: 是

英文摘要：

One-hundred Mayo Clinic patients with high/intermediate-risk myelofibrosis (MF) received momelotinib (MMB; JAK1/2 inhibitor) between 2009 and 2010, as part of a phase 1/2 trial (NCT00935987); 73% harbored JAK2 mutations, 16% CALR, 7% MPL, 44% ASXL1, and 18% SRSF2. As of July 2017, MMB was discontinued in 91% of the patients, after a median treatment duration of 1.4 years. Grade 3/4 toxicity included thrombocytopenia (34%) and liver/pancreatic test abnormalities (<10%); grade 1/2 peripheral neuropathy occurred in 47%. Clinical improvement (CI) occurred in 57% of patients, including 44% anemia and 43% spleen response. CI was more likely to occur in ASXL1-unmutated patients (66% vs 44%) and in those with <2% circulating blasts (66% vs 42%). Response was more durable in the presence of CALR type 1/like and absence of very high-risk karyotype. In multivariable analysis, absence of CALR type 1/like (HR 3.0; 95% CI 1.2–7.6) and presence of ASXL1 (HR 1.9; 95% CI 1.1–3.2) or SRSF2 (HR 2.4, 95% CI 1.3–4.5) mutations adversely affected survival. SRSF2 mutations (HR 4.7, 95% CI 1.3–16.9), very high-risk karyotype (HR 7.9, 95% CI 1.9–32.1), and circulating blasts ≥2% (HR 3.9, 95% CI 1.4–11.0) predicted leukemic transformation. Post-MMB survival (median 3.2 years) was not significantly different than that of a risk-matched MF cohort not receiving MMB.

摘要翻译： 

2009年至2010年间，100名梅奥诊所的高危/中危骨髓纤维化（MF）患者作为1/2期试验（NCT00935987）的一部分接受了莫美洛替尼（MMB；JAK1/2抑制剂）治疗；73%携带JAK2突变，16%携带CALR突变，7%携带MPL突变，44%携带ASXL1突变，18%携带SRSF2突变。截至2017年7月，91%的患者停用了MMB，中位治疗持续时间为1.4年。3/4级毒性包括血小板减少症（34%）和肝/胰腺检测异常（<10%）；47%的患者出现1/2级周围神经病变。57%的患者出现临床改善（CI），包括44%的贫血改善和43%的脾脏反应。临床改善更可能发生在ASXL1未突变患者中（66% vs 44%）以及循环原始细胞<2%的患者中（66% vs 42%）。在存在CALR 1型/类似型和不存在极高危核型的情况下，反应更持久。在多变量分析中，缺乏CALR 1型/类似型（HR 3.0；95% CI 1.2–7.6）以及存在ASXL1（HR 1.9；95% CI 1.1–3.2）或SRSF2（HR 2.4，95% CI 1.3–4.5）突变对生存有不利影响。SRSF2突变（HR 4.7，95% CI 1.3–16.9）、极高危核型（HR 7.9，95% CI 1.9–32.1）和循环原始细胞≥2%（HR 3.9，95% CI 1.4–11.0）预测了白血病转化。MMB治疗后生存期（中位3.2年）与未接受MMB的风险匹配MF队列无显著差异。

原文链接：

Momelotinib therapy for myelofibrosis: a 7-year follow-up