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Background <p>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.</p> Methods <p>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). </p> Results <p>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). </p> Conclusions <p>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.</p>

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Dabrafenib or trametinib in pediatric Langerhans cell histiocytosis with bone lesions: a retrospective efficacy and safety study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月30日

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  • Haiping Ouyang,
  • Hailun Yao,
  • Chengyuan He,
  • Yu Zhou,
  • Jiacheng Dai,
  • Xiaohan Wang,
  • Jiarong Zeng,
  • Chenyuan Liu,
  • Kai Zhong,
  • Jianwen Xiao,
  • Xing Liu

摘要

Background

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.

Methods

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).

Results

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).

Conclusions

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.