Abstract

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.

摘要

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无效或接受再激活。难治性/复发性 LCH 的理想治疗方式尚未得到证实。本综述旨在确定威罗菲尼（一种 BRAF 通路抑制剂）在 LCH 中的疗效和安全性，尤其是难治性/复发病例。文献检索是使用 PubMed、Embase、CENTRAL 和 SIOP 会议上发表的摘要进行的。描述了 LCH 患者单独或联合使用 vemurafenib 治疗的结果的研究被包括在内。总共筛选了 416 项研究，在应用排除标准后，22 项研究（n  = 107）被纳入最终分析。大多数患者的一线治疗是泼尼松龙加长春碱（n  = 92, 86%)，3 名患者 (3%) 预先开始使用维罗非尼。使用 vemurafenib 的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 名患者 (58%) 最终没有活动性疾病 (NAD)，而 39 名 (36%) 有更好的活动性疾病 (ADB)，总缓解率 (ORR) 为 101/107，即 94.4% (置信区间 0.88；0.98)。vemurafenib 的主要不良反应是皮疹或光敏性 (47%) 和其他皮肤不良事件 (15%)。维罗非尼治疗难治性LCH疗效显着且安全；然而，其开始的时间和治疗的持续时间尚未确定。需要更大规模的前瞻性合作试验来回答适当的治疗持续时间和有效的维持治疗方法。