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Pancreatic involvement due to immune checkpoint inhibitors: a proposed classification

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Background

Drug-induced acute pancreatitis (AP) is uncommon and pancreatic involvement due to immune checkpoint inhibitors (ICI) in published reports relied on the National Cancer Institute’s (NCI) Common Terminology Criteria for Adverse Events (CTCAE). CTCAE definition of AP differs from the revised Atlanta classification diagnostic criteria. This study aims to classify the spectrum of pancreatic involvement in patients receiving ICI therapy into categories built on the revised Atlanta classification.

Methods

A retrospective cohort study of cancer patients receiving cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) inhibitors between 2011 and 2020. Pancreas-specific immune-related adverse events (irAEs) were categorized into AP and pancreatic injury.

Results

Forty-seven patients on ICI therapy met selection criteria. Twenty patients (43%) had AP, while 27 (57%) had pancreatic injury. Fifteen patients (75%) developed mild AP. Five patients progressed to pancreatic atrophy, and two patients (4%) developed exocrine pancreatic insufficiency. In both groups, most patients received nivolumab therapy (70% vs. 67%, p = 0.08) with no difference in mean number of nivolumab doses (9 vs. 10, p = 0.69). There was no correlation between the mean number of nivolumab or pembrolizumab doses and AP events (OR 0.94, p = 0.26, and OR 0.98, p = 0.86), but the duration of ICI therapy was significantly related to pancreatic atrophy (OR 1.01, p = 0.05; 95% CI 1.00–1.02).

Conclusion

Based on the novel classification, majority of pancreatic irAEs were classified as asymptomatic pancreatic injury but with some risk of pancreatic atrophy. This classification can help in assessing patterns of pancreatic involvement, pathogenesis, and treatment decisions.

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Abbreviations

CTCAE:

Common terminology criteria for adverse events

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

EPI:

Exocrine pancreatic insufficiency

ICI:

Immune checkpoint inhibitors

irAEs:

Immune-related adverse events

IRB:

Institutional review board

NCI:

National cancer institute

PD-1:

Programmed cell death protein 1

UNL:

Upper normal limit

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Acknowledgements

The study had no funding support. Robert R. McWilliams received prior compensation from Zentalis Pharmaceuticals for advisory services. All other authors of this manuscript have no conflict of interest to disclose.

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Authors and Affiliations

  1. Division of Gastroenterology, Washington University in Saint Louis, St. Louis, MO, USA

    Motaz Ashkar

  2. Division of Gastroenterology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Shruti Chandra & Santhi Swaroop Vege

  3. Department of Radiology, Mayo Clinic, Rochester, MN, USA

    Hiroaki Takahashi & Naoki Takahashi

  4. Division of Oncology, Mayo Clinic, Rochester, MN, USA

    Robert R. McWilliams

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  1. Motaz Ashkar
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  2. Shruti Chandra
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  4. Hiroaki Takahashi
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Contributions

MA and SSV contributed to conception and design; MA, HT, and SSV contributed to analysis and data interpretation; MA contributed to manuscript writing; MA, SC, HT, NT, RRM, and SSV contributed to critical revision of the article for important intellectual content; MA, SC, HT, NT, RRM, and SSV contributed to final approval of the article; MA and HT contributed to statistical expertise; MA, SC, and HT contributed to collection and assembly of data.

Corresponding author

Correspondence to Santhi Swaroop Vege.

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Conflict of interest

Motaz Ashkar, Shruti Chandra, Hiroaki Takahash, Naoki Takahashi, Santhi Swaroop Vege—no conflict of interest to disclose and no project-related funding support. Robert R. McWilliams—Zentalis Pharmaceuticals advisor, no project-related funding.

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Ashkar, M., Chandra, S., Vege, S.S. et al. Pancreatic involvement due to immune checkpoint inhibitors: a proposed classification. Cancer Immunol Immunother 72, 895–901 (2023). https://doi.org/10.1007/s00262-022-03295-1

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  • DOI: https://doi.org/10.1007/s00262-022-03295-1

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