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.

• Authors: Sabrina Hoa, Linda Laaouad, Janet Roberts, Daniel Ennis, Carrie Ye, Karam Al Jumaily, Janet Pope, Tatiana Nevskaya, Alexandra Saltman, Megan Himmel, Robert Rottapel, Christina Ly, Ines Colmegna, Aurore Fifi-Mah, Nancy Maltez, Annaliese Tisseverasinghe, Marie Hudson, Shahin Jamal
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 70 Issue 8 Pg. 2197-2207 (Aug 2021) ISSN: 1432-0851 [Electronic] Germany
• PMID: 33471137 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

Chemical References

• Antibodies, Monoclonal
• Immunosuppressive Agents
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor

Topics

• Antibodies, Monoclonal (adverse effects, immunology)
• Autoimmune Diseases (immunology)
• Canada
• Female
• Humans
• Immunosuppressive Agents (immunology)
• Immunotherapy (adverse effects)
• Lung Neoplasms (immunology)
• Male
• Medical Oncology (methods)
• Melanoma (immunology)
• Middle Aged
• Programmed Cell Death 1 Receptor (immunology)
• Prospective Studies
• Retrospective Studies
• Rheumatology (methods)