Presence of autoantibodies in serum does not impact the occurrence of immune checkpoint inhibitor-induced hepatitis in a prospective cohort of cancer patients

• Published in: Journal of cancer research and clinical oncology 2022-03, Vol.148 (3), p.647-656
• Main Authors: Purde, Mette-Triin, Niederer, Rebekka, Wagner, Nikolaus B., Diem, Stefan, Berner, Fiamma, Hasan Ali, Omar, Hillmann, Dorothea, Bergamin, Irina, Joerger, Markus, Risch, Martin, Niederhauser, Christoph, Lenz, Tobias L., Früh, Martin, Risch, Lorenz, Semela, David, Flatz, Lukas
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Biomarkers, Tumor - blood; Biomarkers, Tumor - immunology; Cancer; Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; Case-Control Studies; Female; Follow-Up Studies; Hematology; Hepatitis; Hepatitis - blood; Hepatitis - epidemiology; Hepatitis - etiology; Hepatitis - immunology; Histocompatibility antigen HLA; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Internal Medicine; Liver diseases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Male; Medical prognosis; Medicine; Medicine & Public Health; Melanoma; Melanoma - drug therapy; Melanoma - immunology; Melanoma - pathology; Middle Aged; Non-small cell lung carcinoma; Oncology; Original Article – Cancer Research; Original – Cancer Research; Patients; Prognosis; Prospective Studies; Small cell lung carcinoma; Survival Rate; Switzerland - epidemiology
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-021-03870-6

Purpose Immune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients. Methods Data from a prospective biomarker cohort comprising melanoma and non-small cell lung cancer (NSCLC) patients were used to analyze the incidence of ICI-induced hepatitis, putatively associated factors, and outcome. Results 40 patients with melanoma and 91 patients with NSCLC received ICI between July 2016 and May 2019. 11 patients developed ICI-induced hepatitis (8.4%). Prior to treatment, 45.5% of patients in the hepatitis cohort and 43.8% of the control cohort showed elevated titers of autoantibodies commonly associated with autoimmune liver diseases ( p  = 0.82). We found two nominally significant associations between the occurrence of ICI-induced hepatitis and HLA alleles associated with autoimmune liver diseases among NSCLC patients. Of note, significantly more patients with ICI-induced hepatitis developed additional irAEs in other organs ( p  = 0.0001). Neither overall nor progression-free survival was affected in the hepatitis group. Conclusion We found nominally significant associations of ICI-induced hepatitis with two HLA alleles. ICI-induced hepatitis showed no correlation with liver-specific autoantibodies, but frequently co-occurred with irAEs affecting other organs. Unlike other irAEs, ICI-induced hepatitis is not associated with a better prognosis.