Dermatopathological Findings of an Erythema Multiforme‐Like Drug Eruption During Enfortumab Vedotin Plus Pembrolizumab Therapy for Metastatic Urothelial Carcinoma: A Case Report

The combination therapy of enfortumab vedotin and pembrolizumab (EV+Pem) is effective for metastatic urothelial carcinoma. However, the dermatopathological findings for treatment-related adverse events, particularly skin disorders, often remain unclear. We report a 69-year-old male with metastatic renal pelvic cancer who developed a Common Terminology Criteria for Adverse Events (CTCAE) grade 3 erythema multiforme-like drug eruption during EV+Pem on day 8 of cycle 3. Dermatopathological findings by skin biopsy at onset and remission were evaluated with immunohistochemistry, demonstrating improvement in proliferative activity (mitotic figures/Ki-67) in parallel with clinical improvement. Peripheral blood tests showed parallel changes in monocytes and eosinophils with the clinical course of the eruption. Both agents were temporarily discontinued and systemic corticosteroids were initiated, followed by tapering. EV was resumed with two-step dose reduction, while pembrolizumab was resumed at the full dose. However, grade 2 rash recurred and was controlled with prednisolone escalation and subsequent tapering, allowing continued therapy with further EV dose reduction. The metastatic lesions have remained in partial response (PR). The evaluation of dermatopathological findings at onset and remission is important in managing skin disorders associated with the combination therapy of EV and pembrolizumab in patients with metastatic urothelial carcinoma.