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Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers
Ashley M Hopkins1,2, Andrew Rowland1,2, Ganessan Kichenadasse1
1Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Flinders Drive, Bedford Park, Adelaide, South Australia 5042, Australia.
Abstract:
Immune checkpoint inhibitors (ICI) are an important development in the treatment of advanced cancer. A substantial proportion of patients treated with ICI do not respond, and additionally patients discontinue treatment due to adverse effects. While many novel biological markers related to the specific mechanisms of ICI actions have been investigated, there has also been considerable research to identify routinely available blood and clinical markers that may predict response to ICI therapy. If validated, these markers have the advantage of being easily integrated into clinical use for nominal expense. Several markers have shown promise, including baseline and post-treatment changes in leucocyte counts, lactate dehydrogenase and C-reactive protein. While promising, the results between studies have been inconsistent due to small sample sizes, follow-up time and variability in the assessed markers. To date, research on routinely available blood and clinical markers has focussed primarily on ICI use in melanoma, the use of ipilimumab and on univariate associations, but preliminary evidence is emerging for other cancer types, other ICIs and for combining markers in multivariable clinical prediction models.
Insights
Predicting patient response to immune checkpoint inhibitors (ICI) is crucial. This study explores easily accessible blood and clinical markers to identify non-responders and those experiencing adverse effects, aiming for cost-effective integration into cancer care.
Area of Science:
- Oncology
- Immunology
- Biomarker Research
Background:
- Immune checkpoint inhibitors (ICI) represent a significant advancement in treating advanced cancers.
- However, a considerable number of patients do not respond to ICI therapy or discontinue treatment due to adverse effects.
- Identifying predictive markers is essential for optimizing patient selection and treatment outcomes.
Purpose of the Study:
- To investigate routinely available blood and clinical markers for predicting response to immune checkpoint inhibitors (ICI) in cancer patients.
- To assess the potential of these markers for cost-effective integration into clinical practice.
- To address inconsistencies in previous research by exploring broader applications and multivariable models.
Main Methods:
- Review of existing literature on blood and clinical markers associated with ICI response.
- Analysis of markers such as leukocyte counts, lactate dehydrogenase, and C-reactive protein.
- Exploration of preliminary evidence for other cancer types, ICIs, and multivariable prediction models.
Main Results:
- Several routinely available markers, including leukocyte counts, lactate dehydrogenase, and C-reactive protein, have shown promise in predicting ICI response.
- Inconsistencies in results across studies are attributed to small sample sizes, varied follow-up times, and marker assessment variability.
- Emerging evidence suggests potential for markers in diverse cancer types and combination with other ICIs.
Conclusions:
- Routinely available blood and clinical markers hold promise for predicting ICI response and guiding treatment decisions.
- Further validation and multivariable modeling are needed to overcome current inconsistencies and enhance clinical utility.
- Validated markers could enable cost-effective, personalized cancer therapy selection.
