Skip to main content
Top
Published in: Current Gastroenterology Reports 10/2023

17-10-2023 | Autoimmune Pancreatitis

Immune Checkpoint Inhibitor-Induced (Type 3) Autoimmune Pancreatitis

Authors: Anusha Shirwaikar Thomas, Suresh T. Chari

Published in: Current Gastroenterology Reports | Issue 10/2023

Login to get access

Abstract

Purpose of Review

Immune checkpoint inhibitors (ICI) have revolutionized cancer care and work primarily by blocking CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), and/or PD-1 (programmed cell death protein 1), and/or PD-L1 (programmed death-ligand 1), thereby providing highly efficacious anti-tumor activity. However, this unmitigated immune response can also trigger immune related adverse events (irAEs) in multiple organs, with pancreatic irAEs (now referred to as type 3 Autoimmune pancreatitis (AIP) being infrequent.

Recent Findings

Type 3 AIP is a drug-induced, immune mediated progressive inflammatory disease of the pancreas that may have variable clinical presentations viz., an asymptomatic pancreatic enzyme elevation, incidental imaging evidence of pancreatitis, painful pancreatitis, or any combination of these subtypes. Management is largely supportive with intravenous fluid hydration, pain control and holding the inciting medication. Steroids have not been shown to demonstrate a clear benefit in acute management. A rapid development pancreatic atrophy is observed on imaging as early as 1 year post initial injury.

Summary

Type 3 AIP is a chronic inflammatory disease of the pancreas that though predominantly asymptomatic and mild in severity can lead to rapid organ volume loss regardless of type of clinical presentation and despite steroid therapy.
Literature
2.
go back to reference •• Sayed Ahmed A, Abreo M, Thomas A, Chari ST. Type 3 autoimmune pancreatitis (immune checkpoint inhibitor-induced pancreatitis). Curr Opin Gastroenterol. 2022;38(5):516–20. https://doi.org/10.1097/MOG.0000000000000873. This paper provides a comprehensive overview on this novel form of drug induced, immune mediated chronic pancreatic injury- type 3 AIP. •• Sayed Ahmed A, Abreo M, Thomas A, Chari ST. Type 3 autoimmune pancreatitis (immune checkpoint inhibitor-induced pancreatitis). Curr Opin Gastroenterol. 2022;38(5):516–20. https://​doi.​org/​10.​1097/​MOG.​0000000000000873​. This paper provides a comprehensive overview on this novel form of drug induced, immune mediated chronic pancreatic injury- type 3 AIP.
3.
go back to reference •• Thomas AS, Abreo M, Sayed SA, Sireesha Yedururi YW, Chari ST. Autoimmune pancreatitis secondary to Immune checkpoint inhibitor therapy (type 3 AIP): insights into a new disease from serial pancreatic imaging. Gastroenterology. 2023;164(1):154–5. https://doi.org/10.1053/j.gastro.2022.09.042. This retrospective analysis provides insight into the radiological patterns of type 3 AIP as well as the short term radiologic profile of this form of chronic pancreatic injury in the largest database of patients with type 3 AIP. •• Thomas AS, Abreo M, Sayed SA, Sireesha Yedururi YW, Chari ST. Autoimmune pancreatitis secondary to Immune checkpoint inhibitor therapy (type 3 AIP): insights into a new disease from serial pancreatic imaging. Gastroenterology. 2023;164(1):154–5. https://​doi.​org/​10.​1053/​j.​gastro.​2022.​09.​042. This retrospective analysis provides insight into the radiological patterns of type 3 AIP as well as the short term radiologic profile of this form of chronic pancreatic injury in the largest database of patients with type 3 AIP.
4.
go back to reference George J, et al. Incidence of pancreatitis with the use of immune checkpoint inhibitors (ICI) in advanced cancers: a systematic review and meta-analysis. Pancreatology. 2019;19(4):587–94.CrossRefPubMed George J, et al. Incidence of pancreatitis with the use of immune checkpoint inhibitors (ICI) in advanced cancers: a systematic review and meta-analysis. Pancreatology. 2019;19(4):587–94.CrossRefPubMed
5.
go back to reference Su Q et al. Risk of immune-related pancreatitis in patients with solid tumors treated with immune checkpoint inhibitors: systematic assessment with meta-analysis. J Immunol Res. 2018;2018:1027323. Su Q et al. Risk of immune-related pancreatitis in patients with solid tumors treated with immune checkpoint inhibitors: systematic assessment with meta-analysis. J Immunol Res. 2018;2018:1027323.
6.
go back to reference Cramer P, et al. Gastrointestinal and hepatic complications of immune checkpoint inhibitors. Curr Gastroenterol Rep. 2017;19(1):3.CrossRefPubMed Cramer P, et al. Gastrointestinal and hepatic complications of immune checkpoint inhibitors. Curr Gastroenterol Rep. 2017;19(1):3.CrossRefPubMed
7.
go back to reference Abu-Sbeih H et al. Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury. J Immunother Cancer. 2019;7(1):31. Abu-Sbeih H et al. Clinical characteristics and outcomes of immune checkpoint inhibitor-induced pancreatic injury. J Immunother Cancer. 2019;7(1):31.
8.
go back to reference Jing Y, Zhang Y, Wang J, Li K, Chen X, Heng J, Gao Q, Ye Y, Zhang Z, Liu Y, Lou Y, Lin SH, Diao L, Liu H, Chen X, Mills GB, Han L. Association between sex and immune-related adverse events during immune checkpoint inhibitor therapy. J Natl Cancer Inst. 2021;113(10):1396–1404. https://doi.org/10.1093/jnci/djab035. Jing Y, Zhang Y, Wang J, Li K, Chen X, Heng J, Gao Q, Ye Y, Zhang Z, Liu Y, Lou Y, Lin SH, Diao L, Liu H, Chen X, Mills GB, Han L. Association between sex and immune-related adverse events during immune checkpoint inhibitor therapy. J Natl Cancer Inst. 2021;113(10):1396–1404. https://​doi.​org/​10.​1093/​jnci/​djab035.
14.
go back to reference Hsiehchen D, Naqash AR, Espinoza M, Von Itzstein MS, Cortellini A, Ricciuti B, Owen DH, Laharwal M, Toi Y, Burke M, Xie Y, Gerber DE. Association between immune-related adverse event timing and treatment outcomes. Oncoimmunology. 2022;11(1):2017162.CrossRefPubMedPubMedCentral Hsiehchen D, Naqash AR, Espinoza M, Von Itzstein MS, Cortellini A, Ricciuti B, Owen DH, Laharwal M, Toi Y, Burke M, Xie Y, Gerber DE. Association between immune-related adverse event timing and treatment outcomes. Oncoimmunology. 2022;11(1):2017162.CrossRefPubMedPubMedCentral
15.
go back to reference Yang H, Yao Z, Zhou X, Zhang W, Zhang X, Zhang F. Immune-related adverse events of checkpoint inhibitors: insights into immunological dysregulation. Clin Immunol. 2020;213:108377.CrossRefPubMed Yang H, Yao Z, Zhou X, Zhang W, Zhang X, Zhang F. Immune-related adverse events of checkpoint inhibitors: insights into immunological dysregulation. Clin Immunol. 2020;213:108377.CrossRefPubMed
19.
go back to reference •• Zhang T, Wang Y, Shi C, Liu X, Lv S, Wang X, Li W, PMCID. Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis. Front Pharmacol. 2022;13:955701. https://doi.org/10.3389/fphar.2022.955701. This systematic review and meta-analysis conducted to assess the incidence of PI in cancer patients with ICI exposure in randomized controlled trials, shows that combination ICI exposure confers increased risk of type 3 AIP. PD-L1 inhibitors confer a higher risk of type 3 AIP compared to CTLA4 blockers or PD-1 inhibitors. •• Zhang T, Wang Y, Shi C, Liu X, Lv S, Wang X, Li W, PMCID. Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis. Front Pharmacol. 2022;13:955701. https://​doi.​org/​10.​3389/​fphar.​2022.​955701. This systematic review and meta-analysis conducted to assess the incidence of PI in cancer patients with ICI exposure in randomized controlled trials, shows that combination ICI exposure confers increased risk of type 3 AIP. PD-L1 inhibitors confer a higher risk of type 3 AIP compared to CTLA4 blockers or PD-1 inhibitors.
23.
go back to reference Chennamadhavuni A, Abushahin L, Jin N, Presley CJ, Manne A. Risk factors and biomarkers for Immune-Related adverse events: a practical guide to identifying high-risk patients and rechallenging Immune Checkpoint inhibitors. Front Immunol. 2022;13:779691.CrossRefPubMedPubMedCentral Chennamadhavuni A, Abushahin L, Jin N, Presley CJ, Manne A. Risk factors and biomarkers for Immune-Related adverse events: a practical guide to identifying high-risk patients and rechallenging Immune Checkpoint inhibitors. Front Immunol. 2022;13:779691.CrossRefPubMedPubMedCentral
25.
go back to reference Thompson JA, Schneider BJ, Brahmer J, Achufusi A, Armand P, Berkenstock MK, et al. Management of immunotherapy-related toxicities, version 1.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(4):387–405. https://doi.org/10.6004/jnccn.2022.0020. Thompson JA, Schneider BJ, Brahmer J, Achufusi A, Armand P, Berkenstock MK, et al. Management of immunotherapy-related toxicities, version 1.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(4):387–405. https://​doi.​org/​10.​6004/​jnccn.​2022.​0020.
26.
27.
29.
go back to reference Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I, Davies MJ, Ernstoff MS, Fecher L, Ghosh M, Jaiyesimi I, Mammen JS, Naing A, Nastoupil LJ, Phillips T, Porter LD, Reichner CA, Seigel C, Song J-M, Thompson JA, Wang Y, Weber JS, Funchain P, Bollin K. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol 2021;39(36):4073–4126. Schneider BJ, Naidoo J, Santomasso BD, Lacchetti C, Adkins S, Anadkat M, Atkins MB, Brassil KJ, Caterino JM, Chau I, Davies MJ, Ernstoff MS, Fecher L, Ghosh M, Jaiyesimi I, Mammen JS, Naing A, Nastoupil LJ, Phillips T, Porter LD, Reichner CA, Seigel C, Song J-M, Thompson JA, Wang Y, Weber JS, Funchain P, Bollin K. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol 2021;39(36):4073–4126.
30.
go back to reference Puzanov I, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95.CrossRefPubMedPubMedCentral Puzanov I, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95.CrossRefPubMedPubMedCentral
31.
go back to reference Haanen J et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv264-iv6. Haanen J et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(Suppl 4):iv264-iv6.
32.
go back to reference Khurana S et al. Severe fistulizing pancreatitis in a patient with Merkel cell carcinoma treated with avelumab. Eur J Gastroenterol Hepatol. 2020;32(9):1266-7. Khurana S et al. Severe fistulizing pancreatitis in a patient with Merkel cell carcinoma treated with avelumab. Eur J Gastroenterol Hepatol. 2020;32(9):1266-7.
Metadata
Title
Immune Checkpoint Inhibitor-Induced (Type 3) Autoimmune Pancreatitis
Authors
Anusha Shirwaikar Thomas
Suresh T. Chari
Publication date
17-10-2023
Publisher
Springer US
Published in
Current Gastroenterology Reports / Issue 10/2023
Print ISSN: 1522-8037
Electronic ISSN: 1534-312X
DOI
https://doi.org/10.1007/s11894-023-00885-6

Other articles of this Issue 10/2023

Current Gastroenterology Reports 10/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.