Dermatological Toxicities of Tebentafusp, a New Bispecific Drug: Case Series and Literature Review

Tebentafusp, a bispecific TCR-anti-CD3 fusion protein targeting gp100-HLA-A02:01 complexes, is approved for the treatment of unresectable/metastatic uveal melanoma (MUM). In this retrospective, single-centre series, five HLA-A02:01-positive patients received tebentafusp. Four developed cutaneous toxicity (80%) within hours of the first infusion, primarily symmetric erythematoedematous truncal plaques. Other findings included acral xerosis/exfoliation and vitiligo-like lesions. Histology revealed spongiosis with subcorneal pustules, which have not been previously reported. No patients discontinued treatment due to skin toxicity and lesions resolved in a mean of 14.5 days. One patient died due to disease progression. Dermatological events are likely to be on-target effects of gp100+ melanocyte targeting and correlate with CD8+ T cell infiltration. Dermatological involvement is common and manageable, highlighting the need for early dermatological input in patients receiving tebentafusp. Emerging data suggest a possible association between rash and response, which warrants further investigation.