Anti-programmed cell death-1 and anti-programmed cell death ligand-1 immune-related liver diseases: from clinical pivotal studies to real-life experience

Expert Opin Biol Ther. 2020 Sep;20(9):1047-1059. doi: 10.1080/14712598.2020.1762562. Epub 2020 May 19.

Abstract

Introduction: Monoclonal antibodies directed against programmed cell death-1 (anti-PD-1) and its ligand (anti-PD-L1) showed a significant efficacy among different immunogenic metastatic tumors such as melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC). Between immune-related adverse events (irAEs) dependent on immune checkpoint inhibitors (ICPIs), immune-related liver diseases are uncommon and a definitive diagnosis is not always feasible.

Areas covered: We revised data from phase II/III clinical trials and real-world retrospective analyses on liver-related adverse events induced by anti-PD-1 (nivolumab/pembrolizumab) and anti-PD-L1 (atezolizumab) in advanced cancer populations (melanoma, NSCLC and RCC). Furthermore, we described clinical-pathological patterns of immune-related liver diseases in real-life.

Expert opinion: Use of anti-PD-1 and anti-PD-L1 led to a paradigm shift in the management of patients with melanoma, NSCLC and RCC. IrAEs can occur potentially in any tissue, leading to discontinuation of ICPIs, at least in a small proportion of these patients, and to a negative impact on their prognosis. Hepatobiliary immune-related adverse events are underestimated due to inappropriate monitoring. Development of novel diagnostic and therapeutic strategies for cancer patients receiving ICPIs as well as the identification of predictive biomarkers of liver injury could allow a better patients' selection and improve clinical outcomes of immune-related liver diseases.

Keywords: Anti-programmed cell death-1; anti-programmed cell death-ligand 1; cholecystitis; hepatitis; immune checkpoint inhibitors; immune-related liver disease; large-duct cholangitis; small-duct cholangitis.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • B7-H1 Antigen / immunology*
  • B7-H1 Antigen / metabolism
  • Digestive System Diseases / etiology
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Melanoma / drug therapy
  • Nivolumab / adverse effects
  • Nivolumab / therapeutic use
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • atezolizumab