Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients
Biewenga, Maaike; van der Kooij, Monique K; Wouters, Michel W J M; Aarts, Maureen J B; van den Berkmortel, Franchette W P J; de Groot, Jan Willem B; Boers-Sonderen, Marye J; Hospers, Geke A P; Piersma, Djura; van Rijn, Rozemarijn S; Suijkerbuijk, Karijn P M; Ten Tije, Albert J; van der Veldt, Astrid A M; Vreugdenhil, Gerard; Haanen, John B A G; van der Eertwegh, Alfons J M; van Hoek, Bart; Kapiteijn, Ellen
(2021) Hepatology international, volume 15, issue 2, pp. 510 - 519
(Article)
Abstract
BACKGROUND: Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide
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cohort. METHODS: Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3-4 hepatitis and outcome. RESULTS: 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). CONCLUSION: Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.
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Keywords: CTLA-4 inhibitor, Drug-induced Hepatitis, Immune-related adverse events, Ipilimumab, Liver metastasis, Nivolumab, Overall survival, PD-1 inhibitor, Progression-Free Survival, Risk factors, Hepatology, Journal Article
ISSN: 1936-0533
Publisher: Springer New York
Note: Funding Information: This research received no external funding. The Netherlands Organization for Health Research and Development funded the start-up of the Dutch Melanoma Treatment Registry (DMTR). Grant number: 836002002. This grant was awarded under the effectiveness research for high-cost medicine program. From its foundation, the DMTR has been sponsored by BMS, Novartis, Roche Nederland B.V., MSD, and Pierre Fabre via the Dutch Institute for Clinical Auditing (DICA). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Publisher Copyright: © 2021, The Author(s).
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