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. 2021 Dec;114(6):725-734.
doi: 10.1007/s12185-021-03205-8. Epub 2021 Aug 12.

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

Dmitry Evseev  1 , Irina Kalinina  2 , Elena Raykina  2 , Daria Osipova  2 , Zalina Abashidze  2 , Anna Ignatova  2 , Anna Mitrofanova  2 , Alexey Maschan  2 , Galina Novichkova  2 , Michael Maschan  2
Affiliations

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

Dmitry Evseev et al. Int J Hematol. 2021 Dec.

Abstract

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.

Keywords: Histiocytosis; Langerhans cell histiocytosis; Molecular biology.

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