Clinical and pathological characterization of Tebentafusp-associated skin toxicity - a cohort study with 33 patients.

drug-associated rash exanthema gp100 rash tebentafusp uveal melanoma

Journal

Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132

Informations de publication

Date de publication:
29 Aug 2024
Historique:
received: 27 05 2024
revised: 29 07 2024
accepted: 14 08 2024
medline: 1 9 2024
pubmed: 1 9 2024
entrez: 31 8 2024
Statut: aheadofprint

Résumé

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 analysed. Skin toxicity was observed in 78.8% of patients and was classified in five 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<0.001). Monocentric study with a limited number of patients. Tebentafusp frequently induced 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 benefit.

Sections du résumé

BACKGROUND BACKGROUND
Tebentafusp is a novel treatment for patients with metastatic uveal melanoma and often causes cutaneous side effects.
OBJECTIVES OBJECTIVE
The aim of this study was to better characterize these heterogenous cutaneous side effects.
METHODS 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 RESULTS
In total, 33 patients were analysed. Skin toxicity was observed in 78.8% of patients and was classified in five 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<0.001).
LIMITATION CONCLUSIONS
Monocentric study with a limited number of patients.
CONCLUSION CONCLUSIONS
Tebentafusp frequently induced 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 benefit.

Identifiants

pubmed: 39216820
pii: S0190-9622(24)02741-5
doi: 10.1016/j.jaad.2024.08.037
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Auteurs

Dirk Tomsitz (D)

Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University (LMU) Munich, Munich, Germany. Electronic address: dirk.tomsitz@med.uni-muenchen.de.

Katrin Kerl (K)

Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University (LMU) Munich, Munich, Germany; Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Lars Einar French (LE)

Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University (LMU) Munich, Munich, Germany; Dr. Philip Frost, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL.

Lucie Heinzerling (L)

Department of Dermatology and Allergy, University Hospital, Ludwig Maximilian University (LMU) Munich, Munich, Germany; University Hospital Erlangen, Erlangen, Germany.

Classifications MeSH