Cutaneous manifestations induced by check point inhibitors in 120 melanoma patients-The European MelSkinTox study.


Journal

Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037

Informations de publication

Date de publication:
12 Apr 2023
Historique:
received: 29 09 2022
accepted: 07 03 2023
pubmed: 13 4 2023
medline: 13 4 2023
entrez: 12 4 2023
Statut: aheadofprint

Résumé

Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i-treated patients. Severe cutaneous irAE do not often occur but could be life-threatening and may persist despite treatment discontinuation. We aimed to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real-world, phase IV, post-marketing study using a follow-up questionnaire. Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma and cutaneous adverse events, supported by EADO. The dermatoses reported were pooled into four categories: inflammatory dermatosis, bullous diseases, drug-related eruptions and pigmentary diseases. Inflammatory benign dermatoses (n = 63) represented the most common group of reactions (52.5%), followed by drug-related eruptions (n = 24, 20%), pigmentary diseases (n = 23, 19.2%) and bullous diseases (n = 10, 8.3%). Grade II (n = 41, 34.2%) are represented by bullous pemphigoid, eczema, hypodermitis, lichenoid eruption, maculopapular rash, pruritus, psoriasis-like rash, urticarial eruption and vitiligo. Grade III (n = 18, 15.0%) are represented by bullous pemphigoid, lichenoid eruption and rashes. Grade IV (n = 2, 1.7%) is only represented by bullous disease. Most cutaneous IrAEs led to immunotherapy continuation (n = 95, 88.0%). CR is associated with more severe the cutaneous irAEs. We report an average time-to-onset of 208 days and some late-onset events. Our study has characterized the clinical spectrum of cutaneous irAEs, their timing and severity and their relationship with tumour response. Grade I-II cutaneous IrAE are easily managed allowing ongoing anticancer treatment. Severe late-onset cutaneous irAE are not uncommon. A dermatological follow-up helps mitigate the risk of life-threatening adverse events. These findings highlight the importance of oncodermatological involvement in management of patients with melanoma receiving immunotherapy.

Sections du résumé

BACKGROUND BACKGROUND
Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i-treated patients. Severe cutaneous irAE do not often occur but could be life-threatening and may persist despite treatment discontinuation.
METHODS METHODS
We aimed to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real-world, phase IV, post-marketing study using a follow-up questionnaire. Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma and cutaneous adverse events, supported by EADO. The dermatoses reported were pooled into four categories: inflammatory dermatosis, bullous diseases, drug-related eruptions and pigmentary diseases.
RESULTS RESULTS
Inflammatory benign dermatoses (n = 63) represented the most common group of reactions (52.5%), followed by drug-related eruptions (n = 24, 20%), pigmentary diseases (n = 23, 19.2%) and bullous diseases (n = 10, 8.3%). Grade II (n = 41, 34.2%) are represented by bullous pemphigoid, eczema, hypodermitis, lichenoid eruption, maculopapular rash, pruritus, psoriasis-like rash, urticarial eruption and vitiligo. Grade III (n = 18, 15.0%) are represented by bullous pemphigoid, lichenoid eruption and rashes. Grade IV (n = 2, 1.7%) is only represented by bullous disease. Most cutaneous IrAEs led to immunotherapy continuation (n = 95, 88.0%). CR is associated with more severe the cutaneous irAEs. We report an average time-to-onset of 208 days and some late-onset events.
CONCLUSION CONCLUSIONS
Our study has characterized the clinical spectrum of cutaneous irAEs, their timing and severity and their relationship with tumour response. Grade I-II cutaneous IrAE are easily managed allowing ongoing anticancer treatment. Severe late-onset cutaneous irAE are not uncommon. A dermatological follow-up helps mitigate the risk of life-threatening adverse events. These findings highlight the importance of oncodermatological involvement in management of patients with melanoma receiving immunotherapy.

Identifiants

pubmed: 37042810
doi: 10.1111/jdv.19112
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

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Auteurs

J-M L'Orphelin (JM)

Department of Dermatology, Caen-Normandie University Hospital, Caen, France.

J Cassecuel (J)

Nantes Université, Nantes - Angers INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France.

L Kandolf (L)

Department of Dermatology, Medical Faculty Military Medical Academy, Belgrade, Serbia.

C A Harwood (CA)

Department of Dermatology, Second Floor, South Tower, Royal London Hospital, Barts Health NHS Trust Whitechapel, E1 1 BB and Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK.

P Tookey (P)

Department of Dermatology, Second Floor, South Tower, Royal London Hospital, Barts Health NHS Trust Whitechapel, E1 1 BB and Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK.

M H Junejo (MH)

Department of Dermatology, Second Floor, South Tower, Royal London Hospital, Barts Health NHS Trust Whitechapel, E1 1 BB and Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK.

S Hogan (S)

Department of Dermatology, Second Floor, South Tower, Royal London Hospital, Barts Health NHS Trust Whitechapel, E1 1 BB and Centre for Cell Biology and Cutaneous Research, Blizard Institute, Queen Mary University of London, London, UK.

C Lebbé (C)

Department of Dermatology, APHP Hôpital Saint Louis, Paris, France.

Z Appalla (Z)

Second Department of Dermatology, Aristotle University of Thessaloniki, Thessaloniki, Greece.

T-M Kränke (TM)

Department of Dermatology, Medical University of Graz, Graz, Austria.

G Pellacani (G)

Department of Dermatology, University of Modena and Reggio Emilia via del Pozzo 71, Modena, Italy.

D Cerasuolo (D)

Biostatistics and Clinical Research Unit, Caen-Normandy University Hospital, Caen, France.

B Dujovic (B)

Department of Dermatology, Medical Faculty Military Medical Academy, Belgrade, Serbia.

V Del Marmol (V)

Department of Dermatology - Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.

A Forschner (A)

Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.

C Garbe (C)

Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.

V Bataille (V)

Department of Dermatology, Hemel Hempstead Hospital NHS, London, UK.

J M Ressler (JM)

Department of Dermatology, Medical University of Vienna, Vienna, Austria.

P Sollena (P)

Department of Medical Science, Dermatology, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy.

A Dompmartin (A)

Department of Dermatology, Caen-Normandie University Hospital, Caen, France.

K Peris (K)

Department of Medical Science, Dermatology, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy.
Department of Dermatology, Catholic University of Rome, Rome, Italy.

B Dreno (B)

Nantes Université, Nantes - Angers INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France.

Classifications MeSH