Efficacy, safety, and relapse outcomes of MAPK inhibitors in pediatric Langerhans cell histiocytosis: A real-world study.

Langerhans cell histiocytosis (LCH) is a rare, heterogeneous inflammatory myeloid neoplasm. This study focuses to summarize real-world experiences of using mitogen-activated protein kinase (MAPK) inhibitors in managing pediatric LCH. Thirty-six children with LCH received vemurafenib (n = 11), dabrafenib (n = 19), or trametinib (n = 6), either as monotherapy (n = 24) or combined with chemotherapy (n = 12). The median Disease Activity Score declined from 5 at baseline to 1 after 3 months of MAPK inhibitor therapy (p < .0001). Elevated interleukin-2 receptor (IL-2R) and tumor necrosis factor-α (TNF-α) levels were observed in 90.1% and 81.8% of patients, respectively. Median IL-2R and TNF-α levels decreased from 1212 U/mL and 15 ρg/mL at baseline to 494 U/mL and 4.18 ρg/mL at 3 months (p < .0001, p = .002), with no significant differences between MAPK inhibitor alone and combined with chemotherapy groups (p = .7791, p = .7503). The objective response rate at 3 months was 94.4% (34/36). At last follow-up, 20 patients had no active disease (NAD); 13 had NAD with residual diabetes insipidus and/or sclerosing cholangitis; 1 had NAD with neurodegeneration; and 2 died of progressive disease. Among 13 patients who discontinued treatment, relapse occurred more frequently in the monotherapy group (75%) than in the combination group (20%), but the difference was not statistically significant (p = .103). [Correction added on 07 February 2026, after first online publication: The p value has been revised from .047 to .103.]. Grade ≥3 adverse events occurred in 11.1% and resolved with dose adjustment. MAPK inhibitors are effective and well tolerated in pediatric LCH. Combination therapy may reduce relapse risk. Further prospective studies are warranted.