Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease
Reproducible and Sustained Efficacy of Targeted Therapy With Vemurafenib in Patients With BRAFV600E-Mutated Erdheim-Chester Disease
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DOI：
10.1200/jco.2014.57.1950
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发表时间：
2015-02-10
影响因子：
45.3
通讯作者：
Amoura, Zahir
中科院分区：
文献类型：
--
作者：
Haroche, Julien;Cohen-Aubart, Fleur;Amoura, Zahir
目的组织细胞病是一种罕见的疾病，预后不一。在半数朗格汉斯细胞组织细胞增生症（LCH）患者和50%至100%的Erdheim-Chester病（ECD）患者中观察到BRAF（V600 E）突变。我们最近报道了短期疗效的BRAF抑制剂（vemurafenib）在3例患者多系统ECD.Patients和方法Vemurafenib给予8例患者多系统ECD与中枢神经系统和/或心脏受累。所有患者均为一线治疗难治性，并携带BRAF（V600 E）突变。4例患者也有LCH病变。第6个月时的正电子发射断层扫描（PET）扫描反应被用作主要评价标准。次要评价标准是比较基线和末次访视时的PET和心血管和脑浸润（计算机断层扫描和磁共振成像[MRI]）。结果所有患者在维罗非尼治疗6个月时均为部分代谢应答者，最大标准化摄取值的中位数降低为63.5%（范围为41.3%至86.9%）。心脏和主动脉浸润的评估显示，根据RECIST标准的表面测量结果，7例患者部分缓解，1例患者病情稳定。4例幕下中枢神经系统浸润患者在MRI上的病变客观减少。所有患者的一般症状均有改善，对维罗非尼有持续反应，中位随访时间为10.5个月（范围6至16个月）。结论维罗非尼二线治疗BRAF（V600 E）突变ECD有客观、持久的疗效。与黑色素瘤相反，在6至16个月后迄今为止没有出现耐药性。
Purpose Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD.Patients and Methods Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]).Results All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe.Conclusion Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.