Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis

Abstract

We sought to investigate the effectiveness and safety of dabrafenib in children with BRAF V600Emutated 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 (0.6-6.5 years old). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (18.9-43.6 months). There were 14 patients (70%) in the RO + group and 6 patients (30%) in the ROgroup. 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 (ORR) and the overall disease control rate (DCR) 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 (1.0-9.0) months. Grade 2 or 3 adverse effects occurred in 5 patients. Conclusion Some children with BRAF V600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant HLH 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.

Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis

“…The targeted therapy provides a promising treatment option for refractory or relapsed LCH over recent years [ 9 , 10 , 27 ]. However, the targeted drugs seemed unable to eradicate tumor clones clearly, and relapse after discontinuation of targeted therapy remained a significant obstacle for improving the prognosis of patients.…”

“…The entire duration of dabrafenib was 12 months, adjusted according to disease assessment. Then patients were treated with maintenance chemotherapy including mercaptopurine, vindesine, and prednisone for six months [ 27 ].…”

<p>Improvement in Pituitary Imaging After Targeted Therapy in Three Children with BRAF-Mutated Langerhans Cell Histiocytosis with Pituitary Involvement</p>

“…The dosages of dabrafenib and trametinib were, respectively, 2 mg/kg per treatment, once every 12 hours, and 0.5 mg per treatment, once every day, administered orally. 10 The general duration of the course of the targeted treatment was 6 months to 1 year, adjusted according to the disease assessment and patient tolerance of the drug. If the patients had disease progression, increased or persistently positive cf BRAF V600E levels or severe adverse effects, targeted therapy could be discontinued.…”

Langerhans cell histiocytosis as a clonal disease of mononuclear phagocyte system

“…Данный препарат представляет собой селективный ингибитор киназы BRAF; как сообщается, он характеризуется лучшей переносимостью по сравнению с вемурафенибом [53]. По данным педиатрического исследования, проведенного в Китае с участием 20 пациентов, у которых была диагностирована рефрактерная форма ГКЛ, общий уровень объективного ответа на монотерапию дабрафенибом составил 65%, а общий уровень контроля заболевания -75% [54]. Стоит также учитывать тот факт, что при отмене препарата у многих пациентов возникают рецидивы.…”