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. 2023 Dec 7;3(3):361-367.
doi: 10.1016/j.gastha.2023.11.020. eCollection 2024.

Immune Checkpoint Inhibitor-Induced Pancreatic Injury: Clinical and Radiological Profile and Response to Steroids

Anusha Shirwaikar Thomas  1 , Michael Abreo  1 , Ahmed Sayed Ahmed  1 , Sai Prasada Rao Manikonda  2 , Mostafa Eyada  3 , Aaron Issac  4 , Fiyinfoluwa Abraham  4 , Jake Sheraj Jacob  5 , Yinghong Wang  1 , Sireesha Yedururi  1 , Suresh T Chari  1
Affiliations

Immune Checkpoint Inhibitor-Induced Pancreatic Injury: Clinical and Radiological Profile and Response to Steroids

Anusha Shirwaikar Thomas et al. Gastro Hep Adv. .

Abstract

Background and aims: Immune checkpoint inhibitor therapy causes numerous immune-related adverse events, including autoimmune pancreatic injury (AIPI), which results in rapid organ atrophy. We profiled the clinico-radiological features, short-term natural history, and response to steroids of AIPI.

Methods: We retrospectively reviewed medical records of 229/11,165 (2.1%) adult patients with AIPI. One hundred and ten out of 229 (48%) had abdominal computerized tomography (CT) scan at lipase elevation; data of 110 without pancreatic metastases were analyzed. We analyzed serial CT-based pancreas volumetry data in 48 patients with AIPI (32 with normal CT and 16 with pancreatitis on CT at lipase elevation). We examined impact of steroids on pain and disease course.

Results: In AIPI (n = 229), median lipase elevation was 4x upper limit of normal (range: 3-40x). The injury was more often asymptomatic than painful (143/229 (62%) vs 86/229 (38%), P < .000). Majority (83/110 (75%) had normal CT, often in painless vs painful disease: 51/57 (90%) vs 32/53 (60%), P < .001) 25% had interstitial pancreatitis. On serial pancreas volumetry, marked volume (cc) loss occurred 1 year after vs 3 months before lipase elevation in both normal CT (median 81.6 vs 61.3, P = .00) and pancreatitis on CT groups (91.8 vs 60.5, P = .00), ≥20% volume loss occurred in 47% vs 73%, respectively (P = .08). Steroids, when used did not mitigate pain, biochemical relapse, pancreas volume loss or 1-year diabetes incidence (7.2%).

Conclusion: Autoimmune pancreatic injury (AIPI) is uniquely characterized by painless lipase elevation, normal pancreas on CT and rapid pancreatic volume loss on follow-up. Steroids do not appear to have a role in management.

Keywords: CTLA-4; Chronic Pancreatitis; Immune-Related Adverse Events; PD-L1; Pancreatic Atrophy; Steroids; Type 3 AIP.

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Figures

Figure 1
Figure 1
(A) Serial pancreatic volume (median, cm3) in relation to time of lipase elevation among patients with normal CT at presentation of type 3 AIP. (B) Serial pancreatic volume (median, cm3) in relation to time of lipase elevation among patients with pancreatitis on CT at presentation of type 3 AIP. (C) Percentage of patients with ≥ 20% pancreatic volume loss at 1 year with normal CT and pancreatitis on CT at presentation of type 3 AIP in comparison to controls. (D) Serial pancreatic volume (median, cm3) in relation to before and 1 year after ICI exposure among patients with and without pain at presentation of type 3 AIP. (E) Serial pancreatic volume (median, cm3) in relation to before and 1 year after ICI exposure among patients with and without steroid exposure for type 3 AIP. (F) Percentage of patients with ≥ 20% pancreatic volume loss at 1 year with or without steroid exposure at presentation of type 3 AIP.
Figure 2
Figure 2
Imaging changes over time in type 3 AIP. Serial contrast-enhanced CTs of the abdomen and 1 representative patient before the start of immunotherapy in 4 months before the diagnosis of pancreatitis (A) at the time of diagnosis of immune mediated pancreatitis (B) and 1 year after the diagnosis of pancreatitis (C). (B) shows diffuse enlargement of the entire pancreas associated with peripancreatic stranding (arrows). (C) shows pancreatic volume loss without ductal dilatation or calcification or fatty replacement.
Figure A1
Figure A1
Patient selection diagram. ∗Three hundred sixteen patients were found to have > 3 ULN (upper limit of normal) lipase with/without pain. Eighty seven patients were excluded due to other etiology for pancreatitis (gallstone-3, alcohol-2, metastasis-35, drug-21, other-26).
See this image and copyright information in PMC

References

    1. Sury K., Perazella M.A., Shirali A.C. Cardiorenal complications of immune checkpoint inhibitors. Nat Rev Nephrol. 2018;14:571–588. - PubMed
    1. Ramos-Casals M., Brahmer J.R., Callahan M.K., et al. Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers. 2020;6:38. - PMC - PubMed
    1. Sayed Ahmed A., Abreo M., Thomas A., et al. Type 3 autoimmune pancreatitis (immune checkpoint inhibitor-induced pancreatitis) Curr Opin Gastroenterol. 2022;38:516–520. - PubMed
    1. Chari S.T., Kloeppel G., Zhang L., et al. Histopathologic and clinical subtypes of autoimmune pancreatitis: the honolulu consensus document. Pancreatology. 2010;10(6):664–672. - PubMed
    1. Shirwaikar Thomas A., Wang Y. In: Managing immunotherapy related organ toxicities: a practical guide. Wang Y., editor. Springer International Publishing; Cham: 2022. Gastroenterology (GI) pp. 81–96.

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