Abstract
BACKGROUND: The presence of BRAF gene mutations and the treatment with targeted drugs in Langerhans cell histiocytosis (LCH) patients have changed the LCH treatment paradigm and greatly improved the prognosis of LCH patients. Nevertheless, a unified standard for the application dose and discontinuation time of targeted drugs in children has not been established. We collated data from clinical trials and studies for pediatric LCH to provide a more robust understanding of dabrafenib's therapeutic potential and associated adverse events (AEs). METHODS: A systematic review and meta-analysis of nine studies was conducted across five electronic databases to assess the efficacy and safety of dabrafenib in children diagnosed with LCH, synthesizing data to provide a more comprehensive and reliable conclusion based on PRISMA 2020 Checklist. RESULTS: The research protocol was pre-registered with PROSPERO (CRD420251046705). Our analysis revealed that dabrafenib significantly improved treatment outcomes for LCH children with an objective response rate (ORR) of 83% [95% confidence interval (CI): 70-91%], disease control rate (DCR) of 85% (95% CI: 68-94%), 1-year progression-free survival (PFS) of 80% (95% CI: 45-95%) and an acceptable safety profile characterized by manageable AEs (grade ≥3 AEs rate 2%). These outcomes emphasize the latent capacity of dabrafenib as a promising treatment option for pediatric LCH, particularly in cases harboring BRAF alterations. Five studies also monitored the ultimate circulating free BRAF(V600) (E) (cfBRAF(V600) (E)) positive rates, which stood at 49.7% (95% CI: 28.7-70.8%). In the subgroup younger than 2 years, the ORR reached 92% (95% CI: 76-100%). CONCLUSIONS: Our study supports the integration of dabrafenib into treatment protocols for pediatric LCH, especially children younger than 2 years, and highlighting the need for further prospective studies to validate these results and explore its long-term effects, ultimately aiming to enhance patient outcomes and alleviate the burden of this challenging disease.