Donadieu J, Larabi IA, Tardieu M, et al. - Researchers assessed the off-label use of vemurafenib (VMF) to manage BRAF^V600E mutation–positive, refractory, childhood Langerhans cell histiocytosis (LCH) in this study including 54 patients from 12 countries who were administered VMF 20 mg/kg/d and grouped based on risk organ involvement: liver, spleen, and/or blood cytopenia. Adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses as per Disease Activity Score were the main evaluation criteria. The median duration of therapy was 13.9 months (for 855 patient-months). The achievement of 38 complete responses and 16 partial responses at 8 weeks was reported, with a decline from 7 at diagnosis to 0 in the median Disease Activity Score. The most frequent adverse event that was experienced by 74% of patients was skin rash. No secondary skin cancer was documented. The BRAF^V600E clone could not be eradicated by empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-mitogen-activated extracellular signal–regulated kinase agent, vinblastine, etc) used for maintenance. Overall, findings are suggestive of the safety as well as the efficacy of VMF as a treatment option for children with refractory BRAF^V600E-positive LCH.