几乎一半的朗格汉斯细胞组织细胞增生症(LCH)患者对初次诱导化疗难以治疗或经历再激活。难治性/复发性LCH的理想治疗方式尚未得到证实。本综述旨在确定Vemurafenib(一种BRAF通路抑制剂)在LCH中的疗效和安全性。尤其是难治性/复发性病例。文献检索使用PubMed,Embase,中部,以及在SIOP会议上发表的摘要。描述使用vemurafenib治疗的LCH患者的结果的研究,单独或组合,包括在内。共筛选了416项研究,在应用排除标准后,22项研究(n=107)纳入最终分析。大多数患者的一线治疗是泼尼松龙加长春碱(n=92,86%),3例患者(3%)开始使用vemurafenib。vemurafenib首次临床反应的中位时间为一周。达到最佳反应的中位时间为5.25个月。在107名患者中,62例患者(58%)最终没有活动性疾病(NAD),而39例(36%)活动性疾病更好(ADB),使总反应率(ORR)为101/107,即94.4%(CI0.88;0.98)。维罗非尼的主要不良反应为皮疹或光敏性(47%)和其他皮肤不良事件(15%)。Vemurafenib在治疗难治性LCH方面非常有效和安全;然而,开始治疗的时间和持续时间尚待确定。需要更大的前瞻性合作试验来回答合适的治疗持续时间和有效的维持治疗方法。
Almost half of the patients with Langerhans cell histiocytosis (
LCH) are refractory to primary induction chemotherapy or undergo reactivation. The ideal treatment modality for refractory/relapsed
LCH is yet not evidenced. This
review aimed to determine the efficacy and safety of vemurafenib (a BRAF pathway inhibitor) in
LCH, particularly the refractory/relapsed cases. The literature search was conducted using PubMed, Embase, CENTRAL, and abstracts published in the SIOP meetings. Studies that described the outcome of patients of
LCH being treated with vemurafenib, alone or in combination, were included. A total of 416 studies were screened, and after applying exclusion criteria, 22 studies (n = 107) were included in the final analysis. The first-line therapy was prednisolone plus vinblastine for most patients (n = 92, 86%), and vemurafenib was started upfront in 3 patients (3%). The median time to first clinical response with vemurafenib was one week. The median time to best response was 5.25 months. Out of 107 patients, 62 patients (58%) had ultimately no active disease (NAD) while 39 (36%) had active disease better (ADB), making the overall response rate (ORR) of 101/107, ie, 94.4% (CI 0.88; 0.98). The main adverse effects of vemurafenib were rash or photosensitivity (47%) and other cutaneous adverse events (15%). Vemurafenib is highly efficacious and safe in the treatment of refractory
LCH; however, the timing of its commencement and duration of therapy is yet to be established. Larger prospective collaborative trials are needed to answer the appropriate treatment duration and effective maintenance therapy approach.