Antineoplastics

Abstract

DRESS syndrome: case report A 39-year-old woman developed DRESS syndrome during treatment with cobimetinib, dabrafenib, nivolumab, trametinib and vemurafenib for melanoma [not all routes and dosages stated]. The woman, who had no previous medical history, presented in November 2016 with a superficial spreading melanoma along with the BRAF V6000E mutation. In September 2017, a new skin lesion was observed as a secondary lesion of melanoma, which was also positive for the BRAF V600E mutation. An extensive check-up was performed. The positron emission tomography (PET) scan revealed multiple pulmonary hypermetabolic nodules, subcutaneous nodules, axillary adenopathy and left mammary muscle. It was decided to initiate nivolumab (anti-PD1) as first-line immunotherapy. Following three treatments, cerebral MRI was performed in addition to cerebral CT, which showed miliary cerebral metastases. Nivolumab therapy was then discontinued, and a targeted therapy per oral was introduced, based on a combination of iMEK (trametinib, 2 mg/day) and iBRAF (dabrafenib, 150 mg/day). Twelve days following treatment initiation, she presented with facial oedema, fatigue, fever, diffuse maculo-papular eruption with no sign of Nikolsky, enanthem with mouth erosions, conjunctival pain, diarrhoea and nausea. Hypereosinophilia, cholestasis and hepatic cytolysis were indicated. Viral reactivation of Epstein Barr virus (EBV) was evident. The evolution was favourable following cessation of the targeted therapy and local care using hydrocortisone butyrate. It was decided to recommence nivolumab; however, following four new treatments with nivolumab, the woman developed intracranial hypertension. Cerebral scan with injection confirmed that this intracranial hypertension was related to a progression of the disease at the cerebral level. PET scan revealed a dissociated response, with a quasi-disappearance of pulmonary, ganglion and cutaneous lesions and a sharp increase in intracerebral hypermetabolism. Following discussion of the benefit/risk ratio based on a multidisciplinary meeting, it was decided to introduce a second targeted therapy per oral, combining iMEK (cobimetinib; 60 mg/day from day 1 to 21) and iBRAF (vemurafenib; 960 × 2 mg/day from day 1 to 28). Fifteen days following the treatment initiation, she presented with facial and neck oedema, fatigue, maculo-papular itchy eruption with no sign of Nikolsky, odynophagia, cheilitis and enanthem. She had hypereosinophilia, cholestasis and hepatic cytolysis without renal failure. There was also viral reactivation of EBV. The evolution was favourable following discontinuation of the targeted therapy and local care using hydrocortisone butyrate. It was considered that she had developed DRESS syndrome secondary to cobimetinib, dabrafenib, nivolumab, trametinib and vemurafenib treatment.