Dermatologic Toxicities Associated with Tebentafusp for Uveal Melanoma: A Review of Clinical Trials and Real-World Evidence

Tebentafusp is a first-in-class bispecific fusion protein that redirects T cells toward gp100-expressing cells and represents the first systemic treatment shown to improve overall survival in patients with HLA-A*02:01-positive metastatic uveal melanoma. As gp100 is also expressed on normal cutaneous melanocytes, skin toxicity is one of the most common adverse effects of treatment, although it remains relatively underrecognized. This narrative review summarizes the available evidence regarding tebentafusp-related cutaneous toxicity from clinical trials and emerging real-world studies. Across published cohorts, cutaneous adverse events occur in most patients receiving tebentafusp. They typically manifest within hours of the initial infusions as diffuse, frequently photodistributed erythematous eruptions accompanied by pruritus, with both frequency and severity generally decreasing with subsequent treatment. Other reported manifestations include xerosis, edema, pigmentary and hair alterations, including vitiligo-like depigmentation and poliosis, as well as less common urticarial, bullous, and photosensitive reactions. Although the development of early cutaneous toxicity has repeatedly been linked to better survival outcomes, this relationship does not appear to be independent of established prognostic variables. Accordingly, rash should currently be interpreted as a potential indicator of immune activation rather than a validated surrogate for therapeutic efficacy. Most cutaneous reactions are mild and can be effectively managed with emollients, topical corticosteroids, and antihistamines, while permanent discontinuation of therapy is uncommon. With tebentafusp becoming increasingly integrated into routine clinical practice and other gp100-targeted and bispecific T-cell–engaging therapies entering development, recognition of this characteristic dermatologic toxicity profile and early involvement of dermatology will be important for effective supportive care and continuation of treatment. Further prospective studies using standardized terminology are warranted to better define the incidence, prognostic relevance, and optimal management of these cutaneous adverse events.