Emerging treatments
BRAF inhibitors (children)
While BRAF inhibitors are recommended for the treatment of LCH in adults, their use in children is still considered emerging. An observational study of 54 paediatric patients treated with vemurafenib for refractory multi-system LCH reported complete remission in 70% and partial remission in 30% of patients. Median age at diagnosis was 0.9 years (range 0.1 to 6.5 years). Median age at vemurafenib initiation was 1.8 years (range 0.18 to 14 years), with a median follow-up of 22 months, and median treatment duration was 13.9 months. Skin rash was the most frequent adverse event and occurred in 74% of patients. No secondary skin cancer was observed. Therapeutic plasma vemurafenib concentrations seemed to be safe and effective. Vemurafenib discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAF V600E allele load, assessed as circulating cell-free DNA, decreased after starting vemurafenib but remained positive, and was associated with a higher risk of reactivation at vemurafenib discontinuation.[101] A prospective phase 2 trial of vemurafenib, cladribine, and cytarabine in children with LCH and the BRAF V600E mutation is in progress.[110]
Mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors
Among patients with other mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK-ERK) pathway mutations (KRAS, MEK, etc.), targeted agents like MEK inhibitors may be utilised following reports of efficacy.[102][111] Case reports of successful treatment with trametinib in paediatric and adult patients with activating mutations of the MAPK pathway have been published.[112][113] A phase 2 clinical trial investigating the use of cobimetinib in paediatric and adult patients with refractory or relapsed LCH is under way.[114]
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