Standardizing the Digital Signal: How an Ontology of Early Warning Signs Can Predict Cytokine Release Syndrome

The Challenge of Cytokine Release Syndrome in Modern Immunotherapy

The landscape of oncology has been radically altered by the advent of cancer-targeted immunotherapies, particularly chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies. While these treatments offer unprecedented efficacy in previously refractory malignancies, they are frequently complicated by Cytokine Release Syndrome (CRS). CRS is a systemic inflammatory response characterized by the massive release of cytokines, leading to symptoms ranging from mild flu-like illness to life-threatening multi-organ failure. Currently, the management of CRS relies heavily on intermittent clinical assessments and reactive intervention. However, the transient and rapid onset of this syndrome often means that by the time clinical symptoms are obvious, the patient is already in a state of high-grade toxicity. There is an urgent, unmet medical need for methods that can detect the physiological precursors of CRS before they manifest as clinical crises.

Digital health technologies (DHTs) offer a potential solution. By utilizing wearable sensors and continuous monitoring, clinicians can track vital signs in real-time, capturing the subtle physiological shifts—digital biomarkers—that precede overt CRS. However, the field has been hampered by a lack of standardization in what should be measured and how those measures relate to clinical outcomes. A recent study by Medberry et al. (2025) addresses this gap by developing a comprehensive ontology of early warning signs for CRS using a robust mixed-methods approach.