Evaluation of autoantibodies as predictors of treatment response and immune-related adverse events during the treatment with immune checkpoint inhibitors: A prospective longitudinal pan-cancer study.
autoimmunity
cancer
immune checkpoint inhibitor therapy
immune-related adverse events
monoclonal antibodies
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
20
02
2022
received:
01
12
2021
accepted:
04
03
2022
pubmed:
18
3
2022
medline:
20
8
2022
entrez:
17
3
2022
Statut:
ppublish
Résumé
The presence of autoantibodies in the serum of cancer patients has been associated with immune-checkpoint inhibitor (ICI) therapy response and immune-related adverse events (irAEs). A prospective evaluation of different autoantibodies in different cancer entities is missing. In this prospective cohort study, we included a pan-cancer cohort of patients undergoing ICI treatment and measured a comprehensive panel of autoantibodies at treatment start and at the time point of first response evaluation. The presence and induction of autoantibodies (ANA, ENA, myositis, hepatopathy, rheumatoid arthritis) in different cancer entities were assessed and the association between autoantibodies and disease control rate (DCR), objective response rate (ORR), and progression-free survival (PFS), as well as the development of grade 3 or higher irAEs were evaluated by logistic regression models, cox proportional hazard models, and Kaplan-Meier estimators. Of 44 patients with various cancer entities, neither the presence of any positive autoantibody measurement nor the presence of positive antinuclear antibodies (ANA) [≥1:80] at baseline was associated with the examined clinical endpoints (DCR, ORR, PFS) in univariable and multivariable analyses. After 8-12 weeks of ICI treatment, DCR, ORR, and PFS did not significantly differ between patients with and without any positive autoantibody measurement or positive ANA titers. The frequency of irAEs did not differ depending on autoantibody status of the patients. Autoantibodies at treatment initiation or induction after 8-12 weeks of ICI treatment are not associated with treatment efficacy as indicated by DCR, ORR, and PFS or higher grade irAEs.
Sections du résumé
BACKGROUND
The presence of autoantibodies in the serum of cancer patients has been associated with immune-checkpoint inhibitor (ICI) therapy response and immune-related adverse events (irAEs). A prospective evaluation of different autoantibodies in different cancer entities is missing.
MATERIALS AND METHODS
In this prospective cohort study, we included a pan-cancer cohort of patients undergoing ICI treatment and measured a comprehensive panel of autoantibodies at treatment start and at the time point of first response evaluation. The presence and induction of autoantibodies (ANA, ENA, myositis, hepatopathy, rheumatoid arthritis) in different cancer entities were assessed and the association between autoantibodies and disease control rate (DCR), objective response rate (ORR), and progression-free survival (PFS), as well as the development of grade 3 or higher irAEs were evaluated by logistic regression models, cox proportional hazard models, and Kaplan-Meier estimators.
RESULTS
Of 44 patients with various cancer entities, neither the presence of any positive autoantibody measurement nor the presence of positive antinuclear antibodies (ANA) [≥1:80] at baseline was associated with the examined clinical endpoints (DCR, ORR, PFS) in univariable and multivariable analyses. After 8-12 weeks of ICI treatment, DCR, ORR, and PFS did not significantly differ between patients with and without any positive autoantibody measurement or positive ANA titers. The frequency of irAEs did not differ depending on autoantibody status of the patients.
CONCLUSION
Autoantibodies at treatment initiation or induction after 8-12 weeks of ICI treatment are not associated with treatment efficacy as indicated by DCR, ORR, and PFS or higher grade irAEs.
Identifiants
pubmed: 35297215
doi: 10.1002/cam4.4675
pmc: PMC9385593
doi:
Substances chimiques
Autoantibodies
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3074-3083Informations de copyright
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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