Abstract 5096: Clinical feature of immune checkpoint inhibitor-induced pancreatic injury
Authors: Itani Junichiro , Ishikawa Takeshi , Doi Toshifumi , Sone Daiki , Morita Ryuichi , Iwai Naoto , Hirose Ryohei , Inoue Ken , Dohi Osamu , Yoshida Naohisa , Uchiyama Kazuhiko , Takagi Tomohisa , Konishi Hideyuki , Itoh Yoshito 
Published: March 2024

Abstract
Immune checkpoint inhibitors(ICIs) cause multiple adverse inflammatory reactions known as immune-related adverse events(irAEs), but ICI-related pancreatic injury(ICI-PI) is rare. ICI-PI ranges from asymptomatic hyperamylasemia to acute pancreatitis(ICI-AP), and its clinical features are not fully understood. We investigated the frequency and clinical features of ICI-PI and ICI-AP as well as their possible risk factors. Of the 186 consecutive cases who received ICI for GI cancers in our hospital from January 2020 to May 2022, 185 could be evaluated for serum amylase(AMY) levels pre- and post- ICI treatment. We retrospectively examined the clinical features and predictors of ICI-PI. Hyperamylasemia of grade 2 or higher according to CTCAE(v.5.0) was considered ICI-PI, and cases with other obvious factors were excluded. In the case of ICI-AP, we analyzed the pathological features of the tissues collected by EUS-FNA as well as the clinical features. The median of ICI doses was 6.0(range, 1-64), and the median duration of observation was 236 days(range, 17-1162). There were 25 cases of hyperamylasemia (higher than ULN) before starting ICI treatment. After starting ICI treatment, 14 patients(7.6%) developed ICI-PI, in all cases grade 2. The median time to onset of ICI-PI was 37.5 days(7-715). No cases discontinued ICI dosing due to ICI-PI, and no cases developed obvious pancreatic endocrine or exocrine insufficiency during the observation period. Overall survival was significantly longer in cases with ICI-PI than in those without ICI-PI(MST; 855 vs. 347days, p=0.029) and there was a trend toward longer PFS(MST; 160 vs. 96 days, p=0.057). Multivariate analysis revealed that only pretreatment serum AMY level(≥80 U/L) was a significant independent predictor of developing ICI-PI(HR: 5.00, 95% CI: 1.057-23.668, p=0.04). ICI-AP occurred in 2 cases(1.1%), both of them discontinued ICI treatment. Both cases showed enlarged pancreas on CT scan, negative serum IgG4 level, and responded well to steroid therapy. Pathological findings showed lymphoplasma cell infiltration, flower-like fibrosis, and obstructive phlebitis, which were similar to type 1 autoimmune pancreatitis(AIP) in one case. In the other case, neutrophil infiltration was observed in the stroma and epithelium, similar to type 2 AIP. The best overall response was PR in both cases with ICI-AP. The findings of this study indicate that higher pretreatment serum AMY levels may increase the probability of ICI-PI. ICI-PI cases without pancreatitis did not show any pancreatic endocrine or exocrine insufficiency during the observation period without interruption of ICI treatment and had favorable prognosis, but a more long-term evaluation of the impact on pancreatic function is needed. The clinical implications of ICI-related hyperamylasemia and its differences from ICI-AP remain uncertain and need to be explored in the future.
Citation Format: Junichiro Itani, Takeshi Ishikawa, Toshifumi Doi, Daiki Sone, Ryuichi Morita, Naoto Iwai, Ryohei Hirose, Ken Inoue, Osamu Dohi, Naohisa Yoshida, Kazuhiko Uchiyama, Tomohisa Takagi, Hideyuki Konishi, Yoshito Itoh. Clinical feature of immune checkpoint inhibitor-induced pancreatic injury [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5096.