Vemurafenib provides a rapid and robust clinical response in pediatric Langerhans cell histiocytosis with the BRAF V600E mutation but does not eliminate low-level minimal residual disease per ddPCR using cell-free circulating DNA

Background Langerhans cell histiocytosis (LCH) is a disease that arises from myeloid cells that phenotypically resemble Langerhans cells (LC), which is typically driven by the BRAF V600E mutation. High-risk LCH has a poor prognosis. Procedure Fifteen children with BRAF V600E + LCH received vemurafenib between March 2016 and February 2020. The median age at LCH onset was 2 months and the median age at the start of vemurafenib treatment was 22 months. The median disease activity score (DAS) at the start of vemurafenib treatment was 12 points. Results The median duration of vemurafenib treatment was 29 months. All patients responded to treatment, with median DAS of 4 points at week 4 and 1 point at 6 months. Two patients died: 1 of hepatic failure after NSAID overdose and 1 of neutropenic sepsis. Cessation of vemurafenib resulted in relapse in 5 patients and was only possible for 1 patient. Serial measurements of BRAF V600E using cell-free circulating DNA revealed that 7 patients had persistently high mutant allele levels. Conclusion Vemurafenib is effective in children with BRAF V600E + LCH. However, treatment with vemurafenib does not eradicate the disease and its long-term toxicity has not been established.

Automated summary

This study investigated the effectiveness of vemurafenib in children with BRAF V600E + LCH, demonstrating that the drug was effective in treating these children. However, it was found that vemurafenib did not completely eradicate the disease post-treatment, with some patients experiencing relapse after cessation of treatment. Furthermore, the long-term toxicity of vemurafenib has not been established and requires further research.