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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2021-08, Vol.70 (8), p.2197-2207
• Main Authors: Hoa, Sabrina, Laaouad, Linda, Roberts, Janet, Ennis, Daniel, Ye, Carrie, Al Jumaily, Karam, Pope, Janet, Nevskaya, Tatiana, Saltman, Alexandra, Himmel, Megan, Rottapel, Robert, Ly, Christina, Colmegna, Ines, Fifi-Mah, Aurore, Maltez, Nancy, Tisseverasinghe, Annaliese, Hudson, Marie, Jamal, Shahin
• Format: Article
• Language: English
• Subjects: Adverse events; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - immunology; Arthritis; Autoimmune diseases; Autoimmune Diseases - immunology; Canada; Cancer immunotherapy; Cancer Research; Corticosteroids; CTLA-4 protein; Female; Humans; Immune checkpoint inhibitors; Immunology; Immunosuppression; Immunosuppressive agents; Immunosuppressive Agents - immunology; Immunotherapy; Immunotherapy - adverse effects; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory diseases; Lung cancer; Lung Neoplasms - immunology; Male; Medical Oncology - methods; Medicine; Medicine & Public Health; Melanoma; Melanoma - immunology; Middle Aged; Oncology; Original; Original Article; Patients; PD-1 protein; Polyarthritis; Programmed Cell Death 1 Receptor - immunology; Prospective Studies; Psoriasis; Psoriatic arthritis; Retrospective Studies; Rheumatic diseases; Rheumatoid arthritis; Rheumatology - methods; Tenosynovitis
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-021-02851-5

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.