Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study

Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with potentially fatal consequences, and about 2/3 of cases involve the BRAF^V600E kinase-activated mutation. Vemurafenib, a BRAF inhibitor, has demonstrated significant clinical improvements in LCH. However, the high relapse rate of LCH following cessation of vemurafenib therapy remains a major challenge, and alternative treatment strategies require further investigation.

In this retrospective multi-center study, we evaluated the efficacy and safety of vemurafenib combined with conventional chemotherapy in patients with severe or refractory LCH.

Seventeen patients were enrolled in the study, with eleven classified as risk organ involvement (RO +). Six received the combination therapy as the primary treatment, and eleven after being refractory to prior chemotherapy. The overall response rate was 94.1%. Progression-free survival among all 17 patients was 70.6% (12/17) at a median follow-up of 32 months, and relapse-free survival among the 15 patients with discontinuation after a response was 73.3%(11/15) at a median follow-up of 34 months. Five of six patients (83.3%) with myeloid BRAF^V600E mutations demonstrated molecular remission. The overall survival rate was 100%. Adverse events were mostly classified as grades 1 or 2.

Our data suggest that the combination of vemurafenib and chemotherapy can achieve sustained clinical and molecular level relief in children with LCH, and side effects are tolerable.