Endocrine adverse events related with immune checkpoint inhibitors: an update for clinicians

Immunotherapy. 2020 May;12(7):481-510. doi: 10.2217/imt-2019-0132. Epub 2020 Apr 29.

Abstract

Designated as scientific breakthrough of current decade, immune checkpoint inhibitors attenuate the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1)/ligand 1 (PD-L1) pathways, depriving cancer cells of a key strategy of evasion from immunosurveillance. The reinvigoration of immune response translates into clinical success, inevitably entwined with a novel constellation of immune-related adverse events. The present review dissects the endocrine immune-related adverse events, emphasizing their unique profile featured by unpredictable onset, irreversibility, nonspecific symptoms, wide clinical spectrum and sophisticated diagnostic work-up. Guidelines advocate individualized decision-making process guided by clinicians' judgement. Future perspective should be governed by five principles - prevention, anticipation, detection, treatment, monitoring - aiming to gain the optimal profit diminishing immunotoxicity.

Keywords: CTLA-4; PD-1; PD-L1; endocrine immune-related adverse events; immune checkpoint inhibitors; immune-related adrenal insufficiency; immune-related diabetes mellitus; immune-related hypophysitis; immune-related thyroid dysfunction.

Publication types

  • Review

MeSH terms

  • Addison Disease / chemically induced
  • Addison Disease / diagnosis
  • Addison Disease / therapy
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • Biomarkers, Pharmacological
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / therapy
  • Endocrine System Diseases / chemically induced*
  • Endocrine System Diseases / diagnosis
  • Endocrine System Diseases / therapy
  • Humans
  • Hypophysitis / chemically induced
  • Hypophysitis / diagnosis
  • Hypophysitis / therapy
  • Immune Checkpoint Inhibitors / adverse effects*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Thyroid Diseases / chemically induced
  • Thyroid Diseases / diagnosis
  • Thyroid Diseases / therapy

Substances

  • B7-H1 Antigen
  • Biomarkers, Pharmacological
  • CTLA-4 Antigen
  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor