Enfortumab vedotin-induced bullous dermatitis

Enfortumab vedotin is a first-in-class antibody-drug conjugate used in the treatment of locally advanced or metastatic urothelial carcinoma. A range of cutaneous adverse events has been reported with enfortumab vedotin use. Nectin-4, a transmembrane protein overexpressed by urothelial carcinoma cells, is the intended target of enfortumab vedotin. However, as nectin-4 is also expressed by epidermal keratinocytes, sweat glands, and hair follicles, it is believed that cutaneous toxicity is mediated though off-target delivery of enfortumab vedotin. We present a patient with metastatic urothelial carcinoma who developed a grade 3 bullous dermatitis after his second treatment cycle of enfortumab vedotin and pembrolizumab therapy. Histopathologic findings showed intraepidermal blisters with prominent dyskeratotic and necrotic keratinocytes. Temporary withholding of enfortumab vedotin and pembrolizumab and treatment with potent topical corticosteroids led to significant improvement and enfortumab vedotin (with pembrolizumab) was resumed at a reduced dosage of enfortumab vedotin without recurrence. We present this case to highlight the clinical manifestations, histopathologic findings, and management of enfortumab vedotin-induced cutaneous toxicity.