文章：

数值变异、等位基因负荷、突变长度及共存突变对新诊断FLT3突变急性髓系白血病中酪氨酸激酶抑制剂疗效的影响

Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia

原文发布日期：2020-05-04

DOI: 10.1038/s41408-020-0318-1

类型: Article

开放获取: 是

英文摘要：

FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). FLT3-ITD diversity can further influence clinical outcomes. Addition of FLT3 inhibitors to standard chemotherapy has improved OS. The aim of this study is to evaluate the prognostic impact of FLT3 diversity and identify predictors of efficacy of FLT3 inhibitors. We reviewed prospectively collected data from 395 patients with newly diagnosed FLT3-ITD mutant AML. 156 (39%) patients received FLT3 inhibitors combined with either high or low intensity chemotherapy. There was no statistically significant difference in clinical outcomes among patients treated with FLT3 inhibitors based on FLT3 numerical variation (p = 0.85), mutation length (p = 0.67). Overall, the addition of FLT3 inhibitor to intensive chemotherapy was associated with an improved OS (HR = 0.35, 95% CI: 0.24–0.5, p = 0.0005), but not in combination with lower intensity chemotherapy (HR = 0.98, 95%CI: 0.7–1.36, p = 0.85). A differential effect of FLT3 inhibitor on OS was more pronounced in younger patients with FLT3 allelic ratio ≥0.5 (HR = 0.41, 95% CI: 0.25–0.66, p < 0.001), single ITD mutation (HR = 0.55, 95% CI: 0.34–0.88, p = 0.01), diploid cytogenetics (HR = 0.52, 95% CI: 0.35–0.76, p = 0.001), NPM1 co-mutation (HR = 0.35, 95% CI: 0.19–0.67, p = 0.001). Our analysis identifies predictors of survival among diverse FLT3 related variables in patients treated with FLT3 inhibitor.
 

摘要翻译： 

在新诊断的急性髓系白血病（AML）中，FLT3-ITD突变与较差的总生存期（OS）相关。FLT3-ITD多样性可进一步影响临床结局。在标准化疗基础上加用FLT3抑制剂改善了OS。本研究旨在评估FLT3多样性的预后影响，并确定FLT3抑制剂疗效的预测因素。我们回顾性分析了前瞻性收集的395例新诊断FLT3-ITD突变AML患者数据。其中156例（39%）患者接受了FLT3抑制剂联合高强度或低强度化疗。根据FLT3数值变异（p=0.85）和突变长度（p=0.67）分组，接受FLT3抑制剂治疗的患者临床结局无统计学显著差异。总体而言，在高强度化疗基础上加用FLT3抑制剂与OS改善相关（HR=0.35，95%CI：0.24-0.5，p=0.0005），但联合低强度化疗时未见此获益（HR=0.98，95%CI：0.7-1.36，p=0.85）。FLT3抑制剂对OS的差异化效应在FLT3等位基因比率≥0.5（HR=0.41，95%CI：0.25-0.66，p<0.001）、单ITD突变（HR=0.55，95%CI：0.34-0.88，p=0.01）、二倍体核型（HR=0.52，95%CI：0.35-0.76，p=0.001）及NPM1共突变（HR=0.35，95%CI：0.19-0.67，p=0.001）的年轻患者中更为显著。本分析明确了FLT3抑制剂治疗患者中多种FLT3相关变量的生存预测因素。

原文链接：

Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia