Tebentafusp use was associated with frequent dermatologic AEs, with desquamation and hypopigmentation observed in non-White patients in a real-world analysis.
Tebentafusp-tebn (Kimmtrak) was associated with high rates of dermatologic adverse effects (AEs), as well as pigmentary changes observed uniquely in non-White patients with metastatic uveal melanoma, according to findings from a single-center retrospective cohort study published in Melanoma Research.1
“Consistent with prior literature, we demonstrated that tebentafusp treatment is associated with frequent dermatologic AEs,” Maggie Zhou, first year medical student at Columbia University Vagelos College of Physicians and Surgeons in New York, New York, and coauthors, wrote in the publication. “We supplement by describing desquamation and hypopigmentation in non-White patients. Therefore, recognition of tebentafusp-associated dermatologic AEs and monitoring for desquamation and pigmentary changes is important, especially among non-White patients,” Zhou added.
Tebentafusp is a bispecific T-cell receptor molecule targeting glycoprotein-100 and CD3 that
Regarding safety, the most frequent AEs occurring in at least 30% of patients were cytokine release syndrome, rash, pyrexia, pruritus, fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting. The most common laboratory abnormalities occurring in at least 50% of patients were decreased lymphocyte count, increased creatinine, increased glucose, increased aspartate aminotransferase, increased alanine aminotransferase, decreased hemoglobin, and decreased phosphate.
The characterization of dermatologic AEs associated with tebentafusp has historically been tied to a predominantly White population, with 87% of participants in the pivotal, phase 2 IMCgp100-202 trial (NCT03070392) being White.3 The study authors sought to evaluate such events at their institution to determine their generalizability within more racially diverse cohorts.1
Demographics, clinical features, dermatologic AEs, and outcomes were reviewed retrospectively in patients with metastatic uveal melanoma who had received tebentafusp at Weill Cornell between January 2021 and May 2025. Common Terminology Criteria for Adverse Events (CTCAE) v6.0 was used to evaluate the severity of dermatologic AEs. Disease-specific mortality rates were compared between patients with and without these events using Fisher exact tests.
If the P value was less than 0.05, the authors could claim significance.
Seventeen patients were included in the analysis. The mean age at the start of treatment was 65.7 years. Most patients were male (58.8%) and White (76.5%); the remainder were Asian (5.9%) and other (5.9%). The mean treatment duration was 274 days. Thirteen patients (76.5%) reported a tebentafusp-associated rash, which was further characterized as maculopapular (76.9%), acneiform (15.4%), or urticarial (7.7%). Most cases presented after the first infusion of tebentafusp (84.6%) and in a sun-exposed distribution (53.8%) or otherwise involved the entire skin (30.8%). Recurrent rashes occurred in 53.8% of patients. Rash severity was as follows: grade 1 (23.1%), grade 2 (38.5%), and grade 3 (38.5%).
Other dermatologic AEs included pruritus (76.5%), edema (35.3%), and xerosis (23.5%). Desquamation (5.9%) and hypopigmentation (5.9%) occurring after rash onset were reported only in non-White patients. Discontinuation occurred in 7 patients (41.2%).
“We found that dermatologic AEs, especially rash, occurred in most tebentafusp-treated patients,” the authors noted, which is consistent with other studies of tebentafusp.
Single-cell RNA sequencing from 11 patients also showed evidence of pigmentation-associated gene downregulation, increased melanocyte apoptosis, T-cell cytotoxicity, and proinflammatory cytokines, supporting the likelihood of a vitiligo-like mechanism, Zhou noted.
“Skin biopsy was performed in 2 patients. One showed CD4 T-cell–mediated interface dermatitis with eosinophils and neutrophils. The other demonstrated low-grade lymphocytic vasculitis with interface and eczematous epidermal changes, consistent with systemic type 4 hypersensitivity,” Zhou stated.
Overall and disease-specific mortality rates were 35.3 and 23.5%, respectively. Disease-specific mortality rates in patients with and without dermatologic AEs were comparable at 23.1% and 50.0%, respectively (P = .538), according to the study authors .
“Multicenter studies including non-White patients are needed to confirm these findings and evaluate associations between dermatologic AEs and outcomes,” Zhou concluded.
