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Investigational Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Event Prediction and Diagnosis
Mitchell S von Itzstein1, Shaheen Khan2,3, David E Gerber1,3,4
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
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.
Insights
Immune checkpoint inhibitors (ICIs) offer cancer treatment advances but can cause immune-related adverse events (irAEs). Research is exploring novel biomarkers to predict and diagnose these potentially severe toxicities, improving patient safety.
Area of Science:
- Oncology
- Immunology
- Translational Medicine
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy.
- However, ICIs can induce immune-related adverse events (irAEs), affecting various organs and posing significant risks.
- The diagnosis and prediction of irAEs are complicated by diverse presentations and unpredictable timing.
Purpose of the Study:
- To review current and emerging biomarkers for the diagnosis and prediction of irAEs.
- To highlight the need for improved patient safety and selection for ICI therapy.
Main Methods:
- Review of conventional laboratory markers used for irAE monitoring.
- Investigation of novel biomarker candidates, including blood cell analysis, cytokines, autoantibodies, genetic factors, immune-cell subsets, T-cell repertoire, microbiome, tumor genomics, and radiomics.
Main Results:
- Traditional lab markers offer limited specificity for irAE diagnosis.
- Numerous novel biomarkers are under active investigation for improved irAE prediction and diagnosis.
- Biomarkers primarily aim to characterize patient immune function.
Conclusions:
- Novel biomarkers hold promise for enhancing the diagnosis and prediction of irAEs.
- Further research into these biomarkers is crucial for improving patient outcomes and safety during ICI therapy.
