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

Maaike Biewenga; Monique K van der Kooij; Michel W J M Wouters; Maureen J B Aarts; Franchette W P J van den Berkmortel; Jan Willem B de Groot; Marye J Boers-Sonderen; Geke A P Hospers; Djura Piersma; Rozemarijn S van Rijn; Karijn P M Suijkerbuijk; Albert J Ten Tije; Astrid A M van der Veldt; Gerard Vreugdenhil; John B A G Haanen; Alfons J M van der Eertwegh; Bart van Hoek; Ellen Kapiteijn

doi:10.1007/s12072-021-10151-4

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

Maaike Biewenga, Monique K van der Kooij, Michel W J M Wouters, Maureen J B Aarts, Franchette W P J van den Berkmortel, Jan Willem B de Groot, Marye J Boers-Sonderen, Geke A P Hospers, Djura Piersma, Rozemarijn S van Rijn, Karijn P M Suijkerbuijk, Albert J Ten Tije, Astrid A M van der Veldt, Gerard Vreugdenhil, John B A G Haanen, Alfons J M van der Eertwegh, Bart van Hoek, Ellen Kapiteijn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	510-519
Number of pages	10
Journal	Hepatology International
Volume	15
Issue number	2
DOIs	https://doi.org/10.1007/s12072-021-10151-4
Publication status	Published - Apr 2021

Bibliographical note

Funding:
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 efectiveness 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.

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Biewenga, M., van der Kooij, M. K., Wouters, M. W. J. M., Aarts, M. J. B., van den Berkmortel, F. W. P. J., de Groot, J. W. B., Boers-Sonderen, M. J., Hospers, G. A. P., Piersma, D., van Rijn, R. S., Suijkerbuijk, K. P. M., Ten Tije, A. J., van der Veldt, A. A. M., Vreugdenhil, G., Haanen, J. B. A. G., van der Eertwegh, A. J. M., van Hoek, B., & Kapiteijn, E. (2021). Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients. Hepatology International, 15(2), 510-519. https://doi.org/10.1007/s12072-021-10151-4

@article{4a7b71aa692f4e7ba115e059dfae091f,

title = "Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients",

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.",

author = "Maaike Biewenga and \{van der Kooij\}, \{Monique K\} and Wouters, \{Michel W J M\} and Aarts, \{Maureen J B\} and \{van den Berkmortel\}, \{Franchette W P J\} and \{de Groot\}, \{Jan Willem B\} and Boers-Sonderen, \{Marye J\} and Hospers, \{Geke A P\} and Djura Piersma and \{van Rijn\}, \{Rozemarijn S\} and Suijkerbuijk, \{Karijn P M\} and \{Ten Tije\}, \{Albert J\} and \{van der Veldt\}, \{Astrid A M\} and Gerard Vreugdenhil and Haanen, \{John B A G\} and \{van der Eertwegh\}, \{Alfons J M\} and \{van Hoek\}, Bart and Ellen Kapiteijn",

note = "Funding: 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 efectiveness 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.",

year = "2021",

month = apr,

doi = "10.1007/s12072-021-10151-4",

language = "English",

volume = "15",

pages = "510--519",

journal = "Hepatology International",

issn = "1936-0533",

publisher = "Springer",

number = "2",

}

Biewenga, M, van der Kooij, MK, Wouters, MWJM, Aarts, MJB, van den Berkmortel, FWPJ, de Groot, JWB, Boers-Sonderen, MJ, Hospers, GAP, Piersma, D, van Rijn, RS, Suijkerbuijk, KPM, Ten Tije, AJ, van der Veldt, AAM, Vreugdenhil, G, Haanen, JBAG, van der Eertwegh, AJM, van Hoek, B & Kapiteijn, E 2021, 'Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients', Hepatology International, vol. 15, no. 2, pp. 510-519. https://doi.org/10.1007/s12072-021-10151-4

TY - JOUR

T1 - Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

AU - Biewenga, Maaike

AU - van der Kooij, Monique K

AU - Wouters, Michel W J M

AU - Aarts, Maureen J B

AU - van den Berkmortel, Franchette W P J

AU - de Groot, Jan Willem B

AU - Boers-Sonderen, Marye J

AU - Hospers, Geke A P

AU - Piersma, Djura

AU - van Rijn, Rozemarijn S

AU - Suijkerbuijk, Karijn P M

AU - Ten Tije, Albert J

AU - van der Veldt, Astrid A M

AU - Vreugdenhil, Gerard

AU - Haanen, John B A G

AU - van der Eertwegh, Alfons J M

AU - van Hoek, Bart

AU - Kapiteijn, Ellen

N1 - Funding: 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 efectiveness 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.

PY - 2021/4

Y1 - 2021/4

N2 - 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.

AB - 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.

U2 - 10.1007/s12072-021-10151-4

DO - 10.1007/s12072-021-10151-4

M3 - Article

C2 - 33634373

SN - 1936-0533

VL - 15

SP - 510

EP - 519

JO - Hepatology International

JF - Hepatology International

IS - 2

ER -

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

Abstract

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