Investigational Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Event Prediction and Diagnosis

Mitchell S. von Itzstein, Shaheen Khan, David E. Gerber

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of multiple cancers. However, these promising therapies may also cause immune-related adverse events (irAEs) in a substantial proportion of patients. These autoimmune phenomena may affect almost any organ system and may occur at almost any point in therapy. In some instances, these toxicities are life-threatening and potentially permanent. Diverse clinical presentation and unpredictable timing further complicate their anticipation and diagnosis. CONTENT: To improve patient safety and selection for ICI use, biomarkers for irAE diagnosis and prediction are under development. Clinicians may use traditional laboratory markers such as routine chemistries, creatinine clearance, thyroid function tests, and serum cortisol/adrenocorticotrophic hormone to monitor for specific irAEs, but noted aberrations may not necessarily represent an immune-mediated etiology. Novel biomarkers have the potential to be more specific to assist in the diagnosis of irAEs. The prediction of irAEs is more challenging. Apart from a history of autoimmune disease, no other clinical parameters are routinely used to project risk. Biomarker candidates under investigation for irAE diagnosis and prediction include blood cell analysis, chemokines/cytokines, autoantibodies, and genetic predisposition, such as human leukocyte antigen haplotype. Among other emerging candidates are immune-cell subsets, T-cell repertoire, fecal microbiome, tumor genomics, and radiomic characterization. SUMMARY: Several conventional laboratory indexes of end-organ dysfunction are currently in routine clinical use for irAE monitoring and diagnosis. Novel biomarkers for the prediction and diagnosis of these irAEs, which primarily characterize patient immune function, represent an area of active investigation.

Original languageEnglish (US)
Pages (from-to)779-793
Number of pages15
JournalClinical chemistry
Volume66
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Investigational Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Event Prediction and Diagnosis'. Together they form a unique fingerprint.

Cite this