Beyond Biomarkers: Immunophenotyping Emerging as Key to Precision IRAE Management

At the 2025 North American Neuroendocrine Tumor Society (NANETS) Multidisciplinary NET Medical Symposium, Alexa Meara, MD, explored the interface of oncology and rheumatology in the immunotoxicity management context in her presentation entitled, “Current vs Ideal Management of IO Toxicities: Rheumatologist Perspective.”

In an interview with Targeted Oncology®, Meara, clinical associate professor of internal medicine and rheumatologist at the Ohio State University Wexner Medical Center, broke down what predictive biomarkers are being investigated to stratify patients who are most at risk for severe or prolonged immune-related adverse events (IRAEs).

The current challenge in managing IRAEs is the absence of definitive biomarkers for risk stratification and treatment guidance. This knowledge gap is driving a fundamental shift toward precision immunomedicine, specifically through the immunophenotyping of patients.

The future of IRAE management requires clinicians to adopt a holistic view of the patient, recognizing that their preexisting health and genetic history significantly impact toxicity risk. Similar to how rheumatology uses a patient’s history to select targeted biologics (like IL-23 or IL-17 blockers) for arthritis, oncologists should leverage this detailed history to predict a patient's "pathway of least resistance" to inflammation. This predictive knowledge can inform appropriate prophylaxis before treatment or targeted therapy following an IRAE.

The central goal is to achieve focused immune upregulation against the cancer while avoiding the collateral damage of unfocused activation (cytokine storms), which currently necessitates broad immunosuppression with steroids.