Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation
Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation
复制标题
DOI：
10.1182/blood-2012-07-446286
复制
发表时间：
2013-02-28
期刊：
影响因子：
20.3
通讯作者：
Amoura, Zahir
中科院分区：
文献类型：
--
作者：
Haroche, Julien;Cohen-Aubart, Fleur;Amoura, Zahir
组织细胞增多症是一种罕见的原因不明的疾病，其预后具有高度的异质性。在57%的朗格汉斯细胞组织细胞增生症(LCH)和54%的Erdheim-Chester病(ECD)病例中观察到BRAF(V600E)功能获得突变，但在其他类型的组织细胞增多症中未观察到。使用突变的BRAF抑制剂(维莫拉非尼)进行靶向治疗可提高黑色素瘤患者的存活率。在此，我们报告了3例携带BRAF(V600E)突变的多系统难治性ECD患者的维莫拉非尼治疗；2例还伴有皮肤或淋巴结LCH受累。对患者进行了临床、生物学(CRP值)、组织学(皮肤活检)和形态(正电子发射断层扫描(PET)、计算机断层扫描和磁共振成像)的评估。对于所有患者，维莫拉非尼治疗导致了显著和迅速的临床和生物改善，治疗开始1个月后，PET、计算机断层扫描和/或磁共振成像证实了肿瘤反应。对于第一个接受治疗的患者，在治疗的1到4个月之间，PET反应增加。经过4个月的随访，治疗仍然有效，尽管仍观察到持续的疾病活动。Vemurafenib是一种新批准的BRAF抑制剂，应该考虑用于患有严重和难治性BRAF(V600E)组织细胞增多症的患者，特别是当这种疾病危及生命时。
Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAF(V600E) gain-of-function mutations have been observed in 57% of cases of Langerhans cell histiocytosis (LCH) and 54% of cases of Erdheim-Chester disease (ECD), but not in other types of histiocytoses. Targeted therapy with an inhibitor of mutated BRAF (vemurafenib) improves survival of patients with melanoma. Here, we report vemurafenib treatment of 3 patients with multisystemic and refractory ECD carrying the BRAF(V600E) mutation; 2 also had skin or lymph node LCH involvement. The patients were assessed clinically, biologically (CRP values), histologically (skin biopsy), and morphologically (positron emission tomography [PET], computed tomography and magnetic resonance imaging). For all patients, vemurafenib treatment led to substantial and rapid clinical and biologic improvement, and the tumor response was confirmed by PET, computed tomography, and/or magnetic resonance imaging 1 month after treatment initiation. For the first patient treated, the PET response increased between months 1 and 4 of treatment. The treatment remained effective after 4 months of follow-up although persistent disease activity was still observed. Treatment with vemurafenib, a newly approved BRAF inhibitor, should be considered for patients with severe and refractory BRAF(V600E) histiocytoses, particularly when the disease is life-threatening.