Vemurafenib provides a rapid and robust clinical response in pediatric Langerhans cell histiocytosis with the BRAF V600E mutation but does not eliminate low-level minimal residual disease per ddPCR using cell-free circulating DNA
Vemurafenib provides a rapid and robust clinical response in pediatric Langerhans cell histiocytosis with the BRAF V600E mutation but does not eliminate low-level minimal residual disease per ddPCR using cell-free circulating DNA
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DOI：
10.1007/s12185-021-03205-8
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发表时间：
2021-08-12
影响因子：
2.1
通讯作者：
Maschan, Michael
中科院分区：
文献类型：
--
作者：
Evseev, Dmitry;Kalinina, Irina;Maschan, Michael
背景郎格汉斯细胞组织细胞增生症(LCH)是一种由BRAF V600E突变引起的表型类似朗格汉斯细胞(LC)的髓系细胞引起的疾病。高危LCH预后较差。BRAF V600E+LCH患儿15例，在2016年3月至2020年2月期间接受维莫拉非尼治疗。LCH发病时的中位年龄为2个月，维莫拉非尼治疗开始时的中位年龄为22个月。维莫拉非尼治疗开始时的疾病活动评分(DAS)中位数为12分。结果维莫拉非尼的中位疗程为29个月。所有患者对治疗均有反应，4周时DAS中位数为4分，6个月时为1分。2例死亡：1例死于非甾体抗炎药过量后的肝功能衰竭，1例死于中性粒细胞减少的败血症。维莫拉非尼停药后5例复发，仅1例可能复发。使用无细胞循环DNA对BRAF V600E进行系列检测，发现7例患者存在持续高突变等位基因水平。结论维莫拉非尼治疗BRAF V600E+LCH有效。然而，维莫拉非尼的治疗并不能根除这种疾病，其长期毒性尚未确定。
Background Langerhans cell histiocytosis (LCH) is a disease that arises from myeloid cells that phenotypically resemble Langerhans cells (LC), which is typically driven by the BRAF V600E mutation. High-risk LCH has a poor prognosis. Procedure Fifteen children with BRAF V600E + LCH received vemurafenib between March 2016 and February 2020. The median age at LCH onset was 2 months and the median age at the start of vemurafenib treatment was 22 months. The median disease activity score (DAS) at the start of vemurafenib treatment was 12 points. Results The median duration of vemurafenib treatment was 29 months. All patients responded to treatment, with median DAS of 4 points at week 4 and 1 point at 6 months. Two patients died: 1 of hepatic failure after NSAID overdose and 1 of neutropenic sepsis. Cessation of vemurafenib resulted in relapse in 5 patients and was only possible for 1 patient. Serial measurements of BRAF V600E using cell-free circulating DNA revealed that 7 patients had persistently high mutant allele levels. Conclusion Vemurafenib is effective in children with BRAF V600E + LCH. However, treatment with vemurafenib does not eradicate the disease and its long-term toxicity has not been established.