Seasonal patterns of toxicity in melanoma patients treated with combination anti-PD-1 and anti-CTLA-4 immunotherapy.

Immune Checkpoint Inhibitors Immune-related Adverse Events Ipilimumab Melanoma Nivolumab Seasonality

Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
26 Dec 2023
Historique:
received: 11 09 2023
revised: 06 12 2023
accepted: 19 12 2023
medline: 8 1 2024
pubmed: 8 1 2024
entrez: 7 1 2024
Statut: aheadofprint

Résumé

Immune checkpoint inhibitors are frequently associated with the development of immunotherapy-related adverse events (irAEs). The exact etiology, including the role of environmental factors, remains incompletely understood. We analyzed the records of 394 melanoma patients from three centers (northern and southern hemisphere). Patients had received at least one cycle of anti-PD-1/anti-CTLA-4 with a minimum follow-up of 3 months. We study the distribution and time to irAEs onset throughout the calendar year. 764 irAEs were recorded; the most frequent were skin rash (35%), hepatitis (32%) and colitis (30%). The irAEs incidence was the highest in autumn and winter, and the ratio for the 'number of irAEs' per 'therapies commenced' was the highest in winter and lowest in summer (2.4 and 1.7, respectively). Season-specific patterns in the time of irAEs onset were observed for pneumonitis (shorter time to onset in autumn, p = 0.025), hepatitis (shorter time to onset in spring, p = 0.016) and sarcoid-like immune reaction (shorter time to onset in autumn, p = 0.041). Season-specific patterns for early-onset irAEs were observed for hepatitis (spring, p = 0.023) and nephritis (summer, p = 0.017). Early-onset pneumonitis was more frequent in autumn-winter (p = 0.008) and early-onset nephritis in spring-summer (p = 0.004). Environmental factors that are associated with particular seasons may contribute to the development of certain irAEs and suggest the potential effect of environmental triggers. The identification of these factors may enhance preventive and therapeutic strategies to reduce the morbidity of irAEs.

Sections du résumé

BACKGROUND BACKGROUND
Immune checkpoint inhibitors are frequently associated with the development of immunotherapy-related adverse events (irAEs). The exact etiology, including the role of environmental factors, remains incompletely understood.
METHODS METHODS
We analyzed the records of 394 melanoma patients from three centers (northern and southern hemisphere). Patients had received at least one cycle of anti-PD-1/anti-CTLA-4 with a minimum follow-up of 3 months. We study the distribution and time to irAEs onset throughout the calendar year.
RESULTS RESULTS
764 irAEs were recorded; the most frequent were skin rash (35%), hepatitis (32%) and colitis (30%). The irAEs incidence was the highest in autumn and winter, and the ratio for the 'number of irAEs' per 'therapies commenced' was the highest in winter and lowest in summer (2.4 and 1.7, respectively). Season-specific patterns in the time of irAEs onset were observed for pneumonitis (shorter time to onset in autumn, p = 0.025), hepatitis (shorter time to onset in spring, p = 0.016) and sarcoid-like immune reaction (shorter time to onset in autumn, p = 0.041). Season-specific patterns for early-onset irAEs were observed for hepatitis (spring, p = 0.023) and nephritis (summer, p = 0.017). Early-onset pneumonitis was more frequent in autumn-winter (p = 0.008) and early-onset nephritis in spring-summer (p = 0.004).
CONCLUSIONS CONCLUSIONS
Environmental factors that are associated with particular seasons may contribute to the development of certain irAEs and suggest the potential effect of environmental triggers. The identification of these factors may enhance preventive and therapeutic strategies to reduce the morbidity of irAEs.

Identifiants

DOI: 10.1016/j.ejca.2023.113506 PMID: 38184928
pubmed: 38184928
pii: S0959-8049(23)00808-0
doi: 10.1016/j.ejca.2023.113506
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113506

Informations de copyright

Copyright © 2024. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Aljosja Rogiers (A)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Florentia Dimitriou (F)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland; Faculty of Medicine, University of Zurich, Zurich, Switzerland.

Irene Lobon (I)

Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.

Catriona Harvey (C)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Charles Perkin Centre, The University of Sydney, Sydney, NSW, Australia.

Ismael A Vergara (IA)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Charles Perkin Centre, The University of Sydney, Sydney, NSW, Australia.

Ines Pires da Silva (I)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia.

Serigne N Lo (SN)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

Richard A Scolyer (RA)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.

Matteo S Carlino (MS)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Westmead and Blacktown Hospitals, Sydney, New South Wales, Australia.

Alexander M Menzies (AM)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia.

Georgina V Long (GV)

Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Department of Medical Oncology, Royal North Shore and Mater Hospitals, Sydney, NSW, Australia. Electronic address: Georgina.long@sydney.edu.au.

Classifications MeSH