This study evaluated the efficacy and safety of dabrafenib or trametinib in pediatric Langerhans cell histiocytosis (LCH) patients with skeletal involvement, for whom conventional therapies offer limited benefit. A single-center retrospective analysis was conducted on 30 children with pathologically confirmed, bone-involved LCH who received dabrafenib or trametinib due to severe, refractory, or chemotherapy-intolerant disease. Primary endpoints were imaging-based objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS) was defined as time from targeted therapy initiation to disease progression (AD-Mixed/AD-Worse) or last follow-up, with AD-Better/AD-Stable considered disease control, including subgroup analysis by BRAF mutation status (V600E vs non-V600E). The median age at diagnosis was 3.1 years with a male-to-female ratio of 2:1. The BRAF V600E mutation was detected in 27 patients (90.0%), with two patients harboring BRAF non-V600E mutations and one patient carrying a MAP2K1 mutation. The median duration of targeted therapy was 17.7 months. At last follow-up, 23.3% (7/30) achieved active disease-better status, and 60.0% (18/30) had active disease-stable status, resulting in an ORR of 23.3% and a DCR of 83.3%. All patients survived. Notably, patients with non-V600E driver mutations (BRAF class II or MAP2K1, cases 22, 26, 28) received MEK inhibitor therapy (trametinib) and derived clinical benefit, highlighting the importance of precise genomic characterization. Drug-related adverse events occurred in 20.0% (6/30) of patients, consisting of mild cutaneous toxicities (e.g., rash, paronychia). In pediatric LCH with bone involvement, particularly in refractory or chemotherapy-intolerant cases, short- to intermediate-term targeted therapy with dabrafenib or trametinib achieved a high disease control rate (83.3%) with a favorable safety profile. Notably, patients with non-V600E driver mutations (BRAF class II or MAP2K1) derived clinical benefit from MEK inhibition, underscoring the importance of comprehensive genomic testing. These real-world findings support the use of targeted therapy in this challenging population.
Ouyang et al. (Mon,) studied this question.