Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAF(V600E)-Mutated Langerhans Cell Histiocytosis

PURPOSE: We sought to investigate the effectiveness and safety of dabrafenib in children with BRAF(V600E)-mutated Langerhans cell histiocytosis (LCH). MATERIALS AND METHODS: A retrospective analysis was performed on 20 children with BRAF(V600E)-mutated LCH who were treated with dabrafenib. RESULTS: The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)(+) group and six patients (30%) in the RO(−) group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAF(V600E) (cfBRAF(V600E)) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. CONCLUSION: Some children with BRAF(V600E)-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.