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%) ( p = .047). 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.