Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

Biewenga, M.; Kooij, M.K. van der; Wouters, M.W.J.M.; Aarts, M.J.B.; Berkmortel, F.W.P.J. van den; Groot, J.W.B. de; ... ; Kapiteijn, E. (2021)

Article / Letter to editor

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 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.

• Ipilimumab
• Nivolumab
• CTLA-4 inhibitor
• PD-1 inhibitor
• Drug-induced Hepatitis
• Risk factors
• Progression-Free Survival
• Overall survival
• Immune-related adverse events
• Liver metastasis

• All authors: Biewenga, M.; Kooij, M.K. van der; Wouters, M.W.J.M.; Aarts, M.J.B.; Berkmortel, F.W.P.J. van den; Groot, J.W.B. de; Boers-Sonderen, M.J.; Hospers, G.A.P.; Piersma, D.; Rijn, R.S. van; Suijkerbuijk, K.P.M.; Tije, A.J. ten; Veldt, A.A.M. van der; Vreugdenhil, G.; Haanen, J.B.A.G.; Eertwegh, A.J.M. van der; Hoek, B. van; Kapiteijn, E.
• Date: 2021-02-25
• Journal: Hepatology International
• Volume: 15
• Issue: 2
• Pages: 510 - 519
• DOI: doi:10.1007/s12072-021-10151-4
• Link: https://link.springer.com/content/pdf/10.1007/s12072-021-10151-4.pdf