Abstract
Purpose
Immune checkpoint inhibitor (ICI) therapy can predispose patients to immune-related adverse events (irAEs) and autoimmune disease (AD) flare-ups, but the characteristics of irAEs among patients with pre-existing ADs are largely unknown. We conducted this study to determine the clinical courses, irAEs, AD flares, treatment, and outcomes of patients with AD on ICIs.
Methods
This was a retrospective study of adult cancer patients at a large cancer center who were diagnosed with ADs before undergoing ICI therapy. Patients’ clinical courses, complications, treatments, and outcomes related to both ADs flares and irAEs were collected and analyzed.
Results
The study included 197 patients. Most (55.4%) were women. Melanoma comprised the highest proportion (28.4%) of malignancies, and most (83.8%) patients received PD-1/PD-L1 inhibitors. Fifty (25.3%) patients developed a new irAE after starting ICI therapy, while 29 (14.7%) patients had an AD flare-up. Patients with inflammatory bowel disease had the highest incidence of AD flare-ups (31.7%), while patients with Hashimoto hypothyroidism had the highest incidence of new irAEs (39.2%). Patients with inflammatory bowel disease had more severe adverse events. In our cohort, patients with a new diagnosis of irAE were treated with immunosuppressive therapy. AD flares were managed similarly. With regard to irAE manifestations, the most common presentations were colitis (24 [12.1%] patients), hepatic transaminase elevations (8 [4%] patients), and pneumonitis (7 [3.5%] patients).
Conclusion
Our findings suggest that patients with gastrointestinal and rheumatologic ADs had a higher incidence of AD flare-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with prior ADs experiencing flare-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment. Thorough evaluation of baseline disease status, appropriate medical management before ICI therapy, and early recognition of inflammatory exacerbation may help ensure long-term success in treating and improving outcomes in these patients.
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Data availability
The data sets used and analyzed in this study are available from the corresponding author upon reasonable request.
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Supported by the NIH/NCI under award number P30CA016672.
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YW was the senior author of the study. She developed the concept, designed the study, interpreted the results, ensured the preservation of data accuracy and integrity at all stages, agreed to be accountable for all aspects of the study, oversaw the overall direction and planning of the study, and contributed to the writing of the manuscript with input from all authors. APM and MS collected the data and created tables/figures. The rest of the authors revised the manuscript. All authors had access to the study data and reviewed and approved the final manuscript.
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Pizuorno Machado, A., Shatila, M., Liu, C. et al. Immune-related adverse events after immune checkpoint inhibitor exposure in adult cancer patients with pre-existing autoimmune diseases. J Cancer Res Clin Oncol 149, 6341–6350 (2023). https://doi.org/10.1007/s00432-023-04582-9
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DOI: https://doi.org/10.1007/s00432-023-04582-9