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

Mette-Triin Purde, Rebekka Niederer, Nikolaus Wagner, Stefan Diem, Fiamma Berner, Omar Hasan Ali, Dorothea Hillmann, Irina Bergamin, Markus Joerger, Martin Risch, Christoph Niederhauser, Tobias L Lenz, Martin Früh, Lorenz Risch, David Semela & Lukas Flatz

abstract

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.
   
citation Purde M T, Niederer R, Wagner N, Diem S, Berner F, Hasan Ali O, Hillmann D, Bergamin I, Joerger M, Risch M, Niederhauser C, Lenz T L, Früh M, Risch L, Semela D, Flatz L. Presence of autoantibodies in serum does not impact the occurrence of immune checkpoint inhibitor-induced hepatitis in a prospective cohort of cancer patients. J Cancer Res Clin Oncol 2021; 148:647-656.
   
type journal paper/review (English)
date of publishing 07-12-2021
journal title J Cancer Res Clin Oncol (148/3)
ISSN electronic 1432-1335
pages 647-656
PubMed 34874490
DOI 10.1007/s00432-021-03870-6