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Predictive Biomarkers of Immune Checkpoint Inhibitors-Related Toxicities
Abstract:
The emergence and continuous development of immune checkpoint inhibitors (ICIs) therapy brings a revolution in cancer therapy history, but the major hurdle associated with their usage is the concomitant ICIs-related toxicities that present a challenge for oncologists. The toxicities may involve non-specific symptoms of multiple systems as for the unique mechanism of formation, which are not easily distinguishable from traditional toxicities. A few of these adverse events are self-limiting and readily manageable, but others may limit treatment, cause interruption and need to be treated with methylprednisolone or tumor necrosis factor-α (TNF-α) antibody infliximab, and even directly threaten life. Early accurate recognition and adequate management are critical to the patient's prognosis and overall survival (OS). Several biomarkers such as the expression of programmed cell death ligand 1 (PD-L1), tumor mutation burden (TMB), and microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) have been proved to be the predictors for anti-tumor efficacy of ICIs, but there is a gap in clinical needs for effective biomarkers that predict toxicities and help filter out the patients who may benefit most from these costly therapies while avoiding major risks of toxicities. Here, we summarize several types of risk factors correlated with ICIs-related toxicities to provide a reference for oncologists to predict the occurrence of ICIs-related toxicities resulting in a timely process in clinical practice.
Insights
Immune checkpoint inhibitors (ICIs) revolutionize cancer treatment but cause toxicities. Identifying risk factors for these toxicities is crucial for safe and effective patient care.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Toxicology
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer therapy.
- However, ICIs can cause significant and sometimes life-threatening toxicities.
- These toxicities often present with non-specific symptoms, complicating diagnosis and management.
Purpose of the Study:
- To review risk factors associated with immune checkpoint inhibitor (ICI)-related toxicities.
- To aid oncologists in predicting and managing these adverse events.
- To improve patient outcomes and optimize the use of costly ICI therapies.
Main Methods:
- Literature review and synthesis of existing data on ICI-related toxicities.
- Identification and categorization of risk factors.
- Summary of current management strategies for ICI-induced adverse events.
Main Results:
- ICI toxicities can range from self-limiting to severe, requiring treatment interruption or specific interventions (e.g., methylprednisolone, infliximab).
- Existing biomarkers (PD-L1, TMB, MSI-H/dMMR) predict anti-tumor efficacy but not toxicity.
- Several risk factors correlate with the occurrence of ICI-related toxicities.
Conclusions:
- Early recognition and management of ICI toxicities are critical for patient prognosis and survival.
- There is a clinical need for biomarkers to predict ICI-related toxicities.
- Understanding risk factors can help oncologists anticipate and mitigate adverse events, improving patient selection and safety.
