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

Background: Tebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects.

Objectives: The aim of this study was to better characterize these heterogenous cutaneous side effects.

Methods: 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.

Results: 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).

Limitation: Monocentric study with a limited number of patients.

Conclusion: 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.