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

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


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.

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / adverse effects*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Cancer Care Facilities / statistics & numerical data
  • Cholecystectomy
  • Cholecystitis / chemically induced
  • Cholecystitis / epidemiology*
  • Cholecystitis / immunology
  • Cholecystitis / therapy
  • Drainage
  • Female
  • Glucocorticoids / therapeutic use
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Retrospective Studies
  • Tertiary Care Centers / statistics & numerical data
  • Treatment Outcome


  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Glucocorticoids
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor