Clinical and pathological characterization of tebentafusp-associated skin toxicity: A cohort study with 33 patients.

Abstract

Tebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects. The aim of this study was to better characterize these heterogenous cutaneous side effects. This prospective cohort study evaluated all patients from a tertiary hospital center who were treated with tebentafusp between January 2019 and June 2023 clinically and assessed skin biopsies histologically. In total, 33 patients were analyzed. Skin toxicity was observed in 78.8% of patients and was classified into 5 clinical categories: (1) symmetrical erythematous patches (83.8%), (2) hemorrhagic macules (11.8%), (3) urticarial lesions (7.4%), (4) bullous lesions (1.5%), and (5) skin (8.5%) and hair depigmentation (11.4%). Histopathologic features were focal lymphocytic interface dermatitis with epidermal infiltration of CD8-positive lymphocytes. Patients with skin reactions had a significantly longer median overall survival compared to patients without any cutaneous events (34 versus 4 months, P < .001). Monocentric study with a limited number of patients. Tebentafusp frequently induces cutaneous reactions. Pathogenesis is likely due to binding of tebentafusp to stimulated melanocytes in the skin, followed by infiltration and activation of lymphocytes. Development of treatment-induced skin reactions may be associated with survival benefits.