An Investigation of Nine Patients with Gastrointestinal Immune-Related Adverse Events Caused by Immune Checkpoint Inhibitors

Digestion. 2020;101(1):60-65. doi: 10.1159/000504647. Epub 2019 Dec 4.

Abstract

Introduction/aims: Immune checkpoint inhibitors (ICIs) sometimes cause immune-related adverse events (irAEs), of which there is little information in the literatures. The objective of this study was to characterize the clinical features of gastrointestinal irAEs (GI irAEs).

Materials and methods: From a total of 250 patients who were administered anti-PD-1 antibodies (nivolumab and pembrolizumab), we retrospectively identified 9 patients with grade 2 or higher GI irAE based on medical records. Patient characteristics, clinical features, imaging and pathological findings, and treatment course were evaluated.

Results: Grade 2 or higher GI irAEs were observed in 9 (3.6%) patients. Of the 9 patients who experienced GI irAE, 8 were male, and mean age was 63.2 years. Five patients received nivolumab and 4 received pembrolizumab. The GI irAEs observed were diarrhea in 7 patients and bloody stool in 2 patients. Grade 2 GI irAEs were identified in 3 patients and grade 3 GI irAEs in 6 patients. The average time from ICI administration to the onset of GI irAEs was 22.2 weeks (range 7-56 weeks) for nivolumab and 19.7 weeks (range 11-28 weeks) for pembrolizumab. Endoscopic findings showed ulcerative colitis-like findings in 3 of 7 patients, and pathological examination revealed crypt epithelial cell apoptosis in 6 of 7 patients. Eight of the 9 patients received steroids, and 2 patients received infliximab additionally. All GI irAEs were manageable.

Conclusions: Because of the lack of specific clinical, imaging, and pathological findings, information of ICI use was indispensable for diagnosis. Although GI irAEs are controllable by steroid and infliximab, further studies regarding management strategy will be needed.

Keywords: Anti PD-1 antibodies; Gastrointestinal immune-related adverse event; Immune checkpoint inhibitors.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Colitis / chemically induced*
  • Colon / drug effects
  • Diarrhea / chemically induced*
  • Female
  • Gastrointestinal Hemorrhage / chemically induced*
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / therapy*
  • Nivolumab / adverse effects
  • Nivolumab / pharmacology
  • Nivolumab / therapeutic use
  • Retrospective Studies

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Cell Cycle Proteins
  • Nivolumab
  • pembrolizumab