Bart van Hoek1, Ellen Kapiteijn2, Maaike Biewenga1, Monique K van der Kooij3, Michel W J M Wouters4,5, Maureen J B Aarts6, Franchette W P J van den Berkmortel7, Jan Willem B de Groot8, Marye J Boers-Sonderen9, Geke A P Hospers10, Djura Piersma11, Rozemarijn S van Rijn12, Karijn P M Suijkerbuijk13, Albert J Ten Tije14, Astrid A M van der Veldt15, Gerard Vreugdenhil16, John B A G Haanen17, Alfons J M van der Eertwegh18. 1. Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands. 2. Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands. h.w.kapiteijn@lumc.nl. 3. Department of Medical Oncology, Leiden University Medical Centre, Leiden, The Netherlands. 4. Department of Medical and Surgical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 5. Scientific Bureau, Dutch Institute for Clinical Auditing, Leiden, The Netherlands. 6. Department of Medical Oncology, Maastricht University Medical Centre+, Maastricht, The Netherlands. 7. Department of Medical Oncology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands. 8. Isala Oncology Centre, Isala, Zwolle, The Netherlands. 9. Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands. 10. Department of Medical Oncology, University Medical Centre Groningen, Groningen, The Netherlands. 11. Department of Internal Medicine, Medisch Spectrum Twente, Enschede, The Netherlands. 12. Department of Internal Medicine, Medical Centre Leeuwarden, Leeuwarden, The Netherlands. 13. Cancer Centre, University Medical Centre Utrecht, Utrecht, The Netherlands. 14. Department of Internal Medicine, Amphia Hospital, Breda, The Netherlands. 15. Departments of Medical Oncology and Radiology and Nuclear Medicine, Erasmus Medical Centre Cancer Institute, Rotterdam, The Netherlands. 16. Department of Internal Medicine, Maxima Medical Centre, Eindhoven/Veldhoven, The Netherlands. 17. Department of Medical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 18. Department of Medical Oncology, Cancer Centre Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
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 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.
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 melanomapatients 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.
Authors: Sander Kelderman; Bianca Heemskerk; Harm van Tinteren; Rob R H van den Brom; Geke A P Hospers; Alfonsus J M van den Eertwegh; Ellen W Kapiteijn; Jan Willem B de Groot; Patricia Soetekouw; Rob L Jansen; Edward Fiets; Andrew J S Furness; Alexandra Renn; Marcin Krzystanek; Zoltan Szallasi; Paul Lorigan; Martin E Gore; Ton N M Schumacher; John B A G Haanen; James M G Larkin; Christian U Blank Journal: Cancer Immunol Immunother Date: 2014-03-08 Impact factor: 6.968
Authors: Mette-Triin Purde; Rebekka Niederer; Nikolaus B 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 Journal: J Cancer Res Clin Oncol Date: 2021-12-07 Impact factor: 4.553