Trametinib Monotherapy in the Treatment of Pediatric Refractory/Relapse Langerhans Cell Histiocytosis

BACKGROUND: Standardized salvage treatments for refractory/relapse Langerhans cell histiocytosis (LCH) remain to be established. Trametinib (TRA) has shown marked efficacy in LCH, but cohort studies regarding efficacy and safety of TRA monotherapy in refractory/relapse LCH were scarce. METHODS/RESULTS: We retrospectively analyzed 22 patients with refractory/relapse LCH treated with TRA monotherapy. Patients were treated for a median of 21.4 months (3.0-51.6 months). Nineteen (86.4%) of 22 of patients remained progression-free during TRA treatment. Sixteen patients stopped TRA (not due to progression or toxicity), of which 10 remained progression free, with median follow-up time of 28.7 months (1.5-44.6 months) after TRA withdrawal, and 6 patients experienced relapse, with median time to relapse from post-TRA withdrawal of 3.7 months (2.7-16.5 months). Two patients continued on TRA at last follow-up and one switched to chemotherapy due to toxicity. Three-year event-free survival was 50.7% (95% CI: 27.7-69.8), with a median follow-up time of 36.4 months (3.0-67.6 months). From TRA initiation to 12 months of treatment, cell-free BRAF/MAP2K1 mutation status in blood presented as negative to negative or positive to negative was correlated with superior event-free survival rate (EFS) rate. Toxicity was tolerable, and adverse events were predominantly skin rash (77.3%), paronychia (22.7%), and diarrhea (13.6%). CONCLUSION: Overall, TRA was effective and safe in the treatment of patients with refractory/relapse LCH, offering a convenient therapeutic alternative.