Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology

Abstract

Background

Limited data are available on the safety and efficacy of immune checkpoint inhibitors (ICI) in patients with preexisting autoimmune diseases (PAD).

Methods

Retrospective study of patients with PAD referred for rheumatologic evaluation prior to starting or during immunotherapy between January 2013 and July 2019 from 10 academic sites across Canada. Data were extracted by chart review using a standardized form.

Results

Twenty-seven patients with PAD on ICI therapy were identified. The most common PADs were rheumatoid arthritis (30%), psoriasis/psoriatic arthritis (30%), inflammatory bowel disease (IBD, 15%) and axial spondyloarthritis (11%), and the most frequently observed cancers were lung cancer and melanoma. All patients received anti-PD-1 therapies, and 2 received additional sequential anti-CTLA-4 therapy. PAD exacerbations occurred in 52% over a median (IQR) follow-up of 11.0 (6.0–17.5) months, with 14% being severe, 57% requiring corticosteroids, 50% requiring immunosuppression and 14% requiring ICI discontinuation. Flares were generally more frequent and severe in patients who previously required more intensive immunosuppression (i.e., biologics). Flares occurred despite background immunosuppression at the time of ICI initiation. In patients with preexisting psoriasis, IBD and axial spondyloarthritis, rheumatic immune-related adverse events (irAEs), mostly polyarthritis and tenosynovitis, were frequently observed. Tumor progression was not associated with exposure to immunosuppressive drugs before or after ICI initiation and was numerically less frequent in patients with irAEs.

Conclusion

PAD exacerbations in the context of ICI treatment are common, although generally mild, and occur despite background immunosuppression. Exacerbations are more frequent and severe in patients on more intensive immunosuppressive therapies pre-immunotherapy.

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Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

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All authors contributed to the study conception and design, or to the acquisition, analysis or interpretation of the data. The first draft of the manuscript was written by Sabrina Hoa and Linda Laaouad, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Sabrina Hoa.

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This submission represents original work that is not under consideration elsewhere and that has not been previously published. All authors participated in the preparation of the manuscript. All authors meet criteria for authorship and will sign a statement attesting authorship, disclosing all potential conflicts of interest and releasing the copyright should the manuscript be acceptable for publication.

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Hoa, S., Laaouad, L., Roberts, J. et al. Preexisting autoimmune disease and immune-related adverse events associated with anti-PD-1 cancer immunotherapy: a national case series from the Canadian Research Group of Rheumatology in Immuno-Oncology. Cancer Immunol Immunother (2021). https://doi.org/10.1007/s00262-021-02851-5

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Keywords

  • Immunotherapy
  • Cancer
  • Preexisting
  • Autoimmune
  • Adverse events
  • Checkpoint inhibitor