PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease

Lorenz Kocheise; Ignazio Piseddu; Joscha Vonderlin; Eric T. Tjwa; Gustav Buescher; Lucy Meunier; Pia Goeggelmann; Francesca Fianchi; Jerome Dumortier; Mar Riveiro Barciela; Tom J. G. Gevers; Benedetta Terziroli Beretta-Piccoli; Maria-Carlota Londono; Sona Frankova; Thomas Roesner; Vincent Joerg; Constantin Schmidt; Fabian Glaser; Jan P. Sutter; Thorben W. Fruendt; Ansgar W. Lohse; Samuel Huber; Johann von Felden; Marcial Sebode; Kornelius Schulze

doi:10.3389/fimmu.2023.1326078

PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease

Lorenz Kocheise^*, Ignazio Piseddu, Joscha Vonderlin, Eric T. Tjwa, Gustav Buescher, Lucy Meunier, Pia Goeggelmann, Francesca Fianchi, Jerome Dumortier, Mar Riveiro Barciela, Tom J. G. Gevers, Benedetta Terziroli Beretta-Piccoli, Maria-Carlota Londono, Sona Frankova, Thomas Roesner, Vincent Joerg, Constantin Schmidt, Fabian Glaser, Jan P. Sutter, Thorben W. FruendtAnsgar W. Lohse, Samuel Huber, Johann von Felden, Marcial Sebode, Kornelius Schulze

^*Corresponding author for this work

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

Abstract

IntroductionImmune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD.MethodsWe contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.ResultsIn this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades >= 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.DiscussionThis European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.

Original language	English
Article number	1326078
Number of pages	9
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1326078
Publication status	Published - 10 Jan 2024

Keywords

autoimmune disease (AID)
immune checkpoint inhibitors (ICI)
autoimmune liver diseases (AILD)
immune related adverse effects (irAEs)
PD-1/PD-L1 immune checkpoint inhibitors
autoimmune hepatitis (AIH)
primary sclerosing cholangites (PSC)
primary biliary cholangitis (PBC)
CHOLANGITIS
RISK

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10.3389/fimmu.2023.1326078Licence: CC BY

1 Erratum / corrigendum / retractions

Corrigendum: PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease
Kocheise, L., Piseddu, I., Vonderlin, J., Tjwa, E. T., Buescher, G., Meunier, L., Goeggelmann, P., Fianchi, F., Dumortier, J., Barciela, M. R., Gevers, T. J. G., Beretta-Piccoli, B. T., Londono, M.-C., Frankova, S., Roesner, T., Joerg, V., Schmidt, C., Glaser, F., Sutter, J. P. & Fruendt, T. W. & 5 others, Lohse, A. W., Huber, S., von Felden, J., Sebode, M. & Schulze, K., 24 Jan 2024, In: Frontiers in Immunology. 15, 2 p., 1369747.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

Open Access

Cite this

Kocheise, L., Piseddu, I., Vonderlin, J., Tjwa, E. T., Buescher, G., Meunier, L., Goeggelmann, P., Fianchi, F., Dumortier, J., Riveiro Barciela, M., Gevers, T. J. G., Terziroli Beretta-Piccoli, B., Londono, M.-C., Frankova, S., Roesner, T., Joerg, V., Schmidt, C., Glaser, F., Sutter, J. P., ... Schulze, K. (2024). PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease. Frontiers in Immunology, 14, Article 1326078. https://doi.org/10.3389/fimmu.2023.1326078

@article{8ef2381afba844148950038b00696d0d,

title = "PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease",

abstract = "IntroductionImmune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD.MethodsWe contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.ResultsIn this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades >= 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.DiscussionThis European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.",

keywords = "autoimmune disease (AID), immune checkpoint inhibitors (ICI), autoimmune liver diseases (AILD), immune related adverse effects (irAEs), PD-1/PD-L1 immune checkpoint inhibitors, autoimmune hepatitis (AIH), primary sclerosing cholangites (PSC), primary biliary cholangitis (PBC), CHOLANGITIS, RISK",

author = "Lorenz Kocheise and Ignazio Piseddu and Joscha Vonderlin and Tjwa, {Eric T.} and Gustav Buescher and Lucy Meunier and Pia Goeggelmann and Francesca Fianchi and Jerome Dumortier and {Riveiro Barciela}, Mar and Gevers, {Tom J. G.} and {Terziroli Beretta-Piccoli}, Benedetta and Maria-Carlota Londono and Sona Frankova and Thomas Roesner and Vincent Joerg and Constantin Schmidt and Fabian Glaser and Sutter, {Jan P.} and Fruendt, {Thorben W.} and Lohse, {Ansgar W.} and Samuel Huber and {von Felden}, Johann and Marcial Sebode and Kornelius Schulze",

year = "2024",

month = jan,

day = "10",

doi = "10.3389/fimmu.2023.1326078",

language = "English",

volume = "14",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

}

Kocheise, L, Piseddu, I, Vonderlin, J, Tjwa, ET, Buescher, G, Meunier, L, Goeggelmann, P, Fianchi, F, Dumortier, J, Riveiro Barciela, M, Gevers, TJG, Terziroli Beretta-Piccoli, B, Londono, M-C, Frankova, S, Roesner, T, Joerg, V, Schmidt, C, Glaser, F, Sutter, JP, Fruendt, TW, Lohse, AW, Huber, S, von Felden, J, Sebode, M & Schulze, K 2024, 'PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease', Frontiers in Immunology, vol. 14, 1326078. https://doi.org/10.3389/fimmu.2023.1326078

TY - JOUR

T1 - PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease

AU - Kocheise, Lorenz

AU - Piseddu, Ignazio

AU - Vonderlin, Joscha

AU - Tjwa, Eric T.

AU - Buescher, Gustav

AU - Meunier, Lucy

AU - Goeggelmann, Pia

AU - Fianchi, Francesca

AU - Dumortier, Jerome

AU - Riveiro Barciela, Mar

AU - Gevers, Tom J. G.

AU - Terziroli Beretta-Piccoli, Benedetta

AU - Londono, Maria-Carlota

AU - Frankova, Sona

AU - Roesner, Thomas

AU - Joerg, Vincent

AU - Schmidt, Constantin

AU - Glaser, Fabian

AU - Sutter, Jan P.

AU - Fruendt, Thorben W.

AU - Lohse, Ansgar W.

AU - Huber, Samuel

AU - von Felden, Johann

AU - Sebode, Marcial

AU - Schulze, Kornelius

PY - 2024/1/10

Y1 - 2024/1/10

N2 - IntroductionImmune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD.MethodsWe contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.ResultsIn this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades >= 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.DiscussionThis European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.

AB - IntroductionImmune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune and cholestatic liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD.MethodsWe contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs.ResultsIn this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades >= 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI.DiscussionThis European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.

KW - autoimmune disease (AID)

KW - immune checkpoint inhibitors (ICI)

KW - autoimmune liver diseases (AILD)

KW - immune related adverse effects (irAEs)

KW - PD-1/PD-L1 immune checkpoint inhibitors

KW - autoimmune hepatitis (AIH)

KW - primary sclerosing cholangites (PSC)

KW - primary biliary cholangitis (PBC)

KW - CHOLANGITIS

KW - RISK

U2 - 10.3389/fimmu.2023.1326078

DO - 10.3389/fimmu.2023.1326078

M3 - Article

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1326078

ER -

PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease

Abstract

Keywords

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Corrigendum: PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune and cholestatic liver disease

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