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. 2022 Aug;11(16):3074-3083.
doi: 10.1002/cam4.4675. Epub 2022 Mar 16.

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

Dominik A Barth  1 , Stefanie Stanzer  1 , Jasmin Spiegelberg  1 , Thomas Bauernhofer  1 , Gudrun Absenger  1 , Florian Posch  1   2 , Rainer Lipp  1 , Michael Halm  1 , Joanna Szkandera  1 , Marija Balic  1 , Armin Gerger  1 , Maria A Smolle  3 , Georg C Hutterer  4 , Christiane Klec  1 , Philipp J Jost  1 , Julia Kargl  5   6 , Martin Stradner  7 , Martin Pichler  1   8
Affiliations

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

Dominik A Barth et al. Cancer Med. 2022 Aug.

Abstract

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.

Keywords: autoimmunity; cancer; immune checkpoint inhibitor therapy; immune-related adverse events; monoclonal antibodies.

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Conflict of interest statement

None of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.

Figures

FIGURE 1|
FIGURE 1|
Kaplan–Meier curves showing progression‐free survival (PFS) for patients with positive versus negative autoantibody screening at treatment initiation
See this image and copyright information in PMC

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