T-cell changes induced by desensitisation to BRAF inhibitors in two patients with DRESS.

Abstract

To the Editor,Melanoma is an aggressive skin cancer, with low survival rates in pa-tients with advanced disease. Melanoma patients present mutationsin genes encoding kinases that participate in the mitogen-activatedprotein kinases (MAPK) cascade, such as RAF, encoded in BRAFgene and MEK.1 The commonest melanoma mutation is the V600E,which produces an abnormal protein that activates the MAPK cas-cade inducing cellular alterations. Besides surgical excision, there are different options according to clinical stage, like the use of drugcombinations as BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi),which inhibit the MAPK cascade activation. 2 This combination in-creases treatment effectiveness, decreases adverse effects andprevents drug resistance. 3 These drugs can induce severe cutane-ous allergic reactions (SCAR). 4 Generally, desensitisation in SCAR iscontraindicated. Moreover, in melanoma patients, desensitisationseems to be the only procedure that allows them to continue withtreatment. We have studied two melanoma patients (P1 and P2)who developed drug rash with eosinophilia and systemic symptoms(DRESS) after BRAFi administration and who tolerated this drugafter desensitisation. We have assessed T-cell involvement in skinbiopsies and peripheral blood samples at acute phase (T0), and im-munological response after desensitisation (T1). Additionally, prolif-erative response was assessed at two times.