What is the role of vemurafenib in the treatment of Langerhans cell histiocytosis (LCH)?

Updated: Jun 12, 2020
  • Author: Christopher R Shea, MD; Chief Editor: William D James, MD  more...
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The discovery of oncogenic BRAF V600E mutation in more than half of LCH specimens [82] suggests that B-RAF inhibitors such as vemurafenib could be applied to treatment of those cases shown to bear that mutation. Vemurafenib was approved for Erdheim-Chester disease (ECD) with BRAF V600 mutation in November 2017. ECD is also known as polyostotic sclerosing histiocytosis. Early case reports describing use of vemurafenib to treat patients with multisystemic and refractory ECD carrying the BRAF V600E mutation showed positive results. Two of the patients also had skin or lymph node LCH involvement. In all three patients, vemurafenib treatment led to clinical and biologic improvement, which was maintained after 4 months of follow up (although persistent disease activity was still observed). [83] A phase 2 VE-BASKET study (n=22) confirmed use of vemurafenib for patients who have ECD with the BRAF V600 mutation. Results from a basket study in 2015 showed a response rate of 43% in the cohort with ECD or LCH. [84] Final results showed a best overall response rate of 54.5%. [85]

In phase 2 of the VE-BASKET trial, four BRAF V600E LCH patients showed a 2-year progression-free survival of 86%, with all patients achieving stable disease or better. Dose reduction was required for every patient, owing to adverse events, including a case of treatment-induced thyroid cancer that resulted in discontinuation of vemurafenib. [86] An international observational study of 54 patients showed vemurafenib to be effective in treating refractory multisystem LCH. At 8 weeks, 38 patients achieved complete responses. However, 24 of 30 patients experienced relapse after drug discontinuation. [36] Additional studies are needed to establish the optimal dosage and duration of vemurafenib treatment.

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