Success of Trametinib in the Treatment of Langerhans Cell Histiocytosis With Novel MAPK Pathway Mutations.

Approximately a third of patients with Langerhans cell histiocytosis (LCH) experience recurrence of disease. Genomic analysis has revealed that this condition is often driven by oncogenic mutations in the MAP kinase (MAPK) pathway, and agents that target components of this pathway have been explored as a second-line treatment for LCH. Here, we examine 2 pediatric patients with LCH and confirmed but rarely reported MAPK pathway mutations treated with trametinib, a MAP2K inhibitor approved to treat several cancers with a BRAFV600E mutation. Each patient achieved or maintained complete resolution of disease and remain on the drug with no adverse effects.