Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer

Invest New Drugs. 2017 Aug;35(4):529-536. doi: 10.1007/s10637-017-0453-0. Epub 2017 Mar 20.

Abstract

Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3.0 mg/kg) every 2 weeks until disease progression or irAEs occurred. Clinical data regarding the duration of nivolumab treatment, symptoms, laboratory abnormalities, pathological findings of liver parenchyma biopsy specimens, and management of nivolumab-related cholangitis were analyzed. Results Our analysis revealed that nivolumab-related cholangitis was characterized by (1) localized extrahepatic bile duct dilation without obstruction; (2) diffuse hypertrophy of the extrahepatic bile duct wall; (3) a dominant increase in the biliary tract enzymes alkaline phosphatase and gamma-glutamyl transpeptidase relative to the hepatic enzymes aspartate and alanine aminotransferase; (4) normal or reduced levels of the serum immunological markers antinuclear antibody, antimitochondrial antibody, smooth muscle antibody, and immunoglobulin G4; (5) the pathological finding of biliary tract cluster of differentiation 8-positive T cell infiltration from liver biopsy; and (6) a moderate to poor response to steroid therapy. Conclusions Nivolumab-related cholangitis is associated with distinct imaging and clinicopathological features that distinguish it from acute cholangitis of common etiologies and other immune-related cholangitis. Further studies are warranted to establish the optimal management of patients with this irAE.

Keywords: Cholangitis; Immune-related adverse event; Nivolumab monotherapy; Programmed death-1.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cholangitis / chemically induced*
  • Cholangitis / diagnostic imaging
  • Cholangitis / pathology
  • Female
  • Humans
  • Liver / diagnostic imaging
  • Liver / pathology
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nivolumab

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Nivolumab