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. 2019 May 3;7(1):118.
doi: 10.1186/s40425-019-0604-2.

Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment

Hamzah Abu-Sbeih  1 , Cynthia Nguyen Tran  2 , Phillip S Ge  1 , Manoop S Bhutani  1 , Mazen Alasadi  1 , Aung Naing  3 , Amir A Jazaeri  4 , Yinghong Wang  5
Affiliations

Case series of cancer patients who developed cholecystitis related to immune checkpoint inhibitor treatment

Hamzah Abu-Sbeih et al. J Immunother Cancer. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) represent a promising novel class of cancer therapy, but immune-mediated adverse events can complicate ICI treatment. Acute cholecystitis in patients receiving ICI therapy has not been characterized. We aimed to describe the clinical features of patients who developed ICI-related cholecystitis.

Methods: We evaluated a case series of patients at a tertiary cancer center who received ICI therapy and developed cholecystitis, diagnosed by clinical presentation and diagnostic imaging, during 2010-2018. Patients with a history of chronic cholecystitis or other etiologies of acute cholecystitis, such as cholelithiasis, were excluded. A chi-square test was used to compare the frequency of cholecystitis between ICI regimens. Kaplan-Meier and log rank analyses were used to compare survival between subgroups.

Results: Of the 4253 patients who received ICIs in the study period, 25 (0.6%) patients developed suspected ICI-related cholecystitis. Alternatively, of the 31,426 cancer-matched patients who received non-ICI therapy, 72 (0.2%) developed acalculous cholecystitis (P < 0.001). Among the 25 included patients, the median time from ICI initiation to cholecystitis was 6 months (range, 0.1-31 months). Fifteen (60%) patients received an inhibitor of programmed death protein 1 (anti-PD-1) or of its ligand (anti-PD-L1) as a single agent, and 10 (40%) patients received an inhibitor of cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) therapy alone or combined with anti-PD-1/L1. Anti-CTLA-4 monotherapy was associated with a higher risk of cholecystitis (P = 0.006). ICI therapy was discontinued in 20 patients, in three (12%) as a result of acute cholecystitis. Two (8%) patients developed sepsis, and four (16%) had perforation of the gallbladder wall. Five (20%) patients underwent surgical cholecystectomy, and eight (32%) underwent percutaneous drainage. Five (20%) patients were treated with steroids; two of them required surgery. Ten (40%) patients were able to restart ICI therapy. Patients who received a combination of anti-CTLA-4 and anti-PD-1/L1 had more complications of cholecystitis than did patients who received either agent alone (P = 0.03).

Conclusions: ICI treatment can result in a clinical condition similar to typical acute cholecystitis in a minority of patients. ICI-related cholecystitis should be managed in a similar fashion to typical cholecystitis. The efficacy of steroids for the treatment of ICI-related cholecystitis is unclear.

Keywords: Adverse event; Cholecystitis; Gallbladder; Immune checkpoint inhibitor; Immune-mediated cholecystitis; Immunotherapy.

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Conflict of interest statement

Ethics approval and consent to participate

The ethics approval of this study was granted by the Institutional Review Board committee at The University of Texas MD Anderson Cancer Center (PA18–0472). Consent was waived for this study.

Consent for publication

This study was granted a waiver for consent.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of included patients
Fig. 2
Fig. 2
Overall survival by steroid treatment
See this image and copyright information in PMC

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