Metabolomics-Derived Pathway Scores Outperform Inflammatory Protein Markers—Delivering Risk Prediction Where Proteomics Falls Short
MORRISVILLE, N.C. – February 17, 2026 – Metabolon, Inc., the global leader in providing metabolomics solutions advancing a wide variety of life science research, diagnostic, therapeutic development, and precision medicine applications, today announced its industry-leading global metabolomics platform was used by researchers from Kite, a Gilead company, for the most extensive metabolomic study ever conducted in the context of CAR T-cell therapy. Leveraging Metabolon’s untargeted Global Discovery Panel, Kite researchers analyzed more than 3,800 longitudinal serum and plasma samples—and a rare set of cerebrospinal fluid (CSF) samples—from patients treated with the FDA-approved anti-CD19 CAR T-cell therapies axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel).
The multi-trial meta-cohort, spanning six clinical studies, enabled investigators to uncover metabolic pathways strongly associated with severe neurological events (NEs), a significant and sometimes life-threatening toxicity of CAR T-cell therapy. Despite the transformative efficacy of CAR T-cell treatments for large B-cell lymphoma (LBCL), mantle cell lymphoma, follicular lymphoma, and B-cell acute lymphoblastic leukemia, the biological drivers of neurotoxicity have remained poorly understood.
“This study demonstrates how metabolomics uniquely exposes the biological pathways driving CAR T-cell–associated neurotoxicity, insights that are not accessible through proteomics or cytokine profiling alone,” said Heino Heyman, Director of Global Field Metabolomics Sciences at Metabolon. “By mapping disruptions in tryptophan catabolism, NMDA-linked excitotoxicity, and polyamine metabolism, the analysis not only identified patients at risk for severe neurologic events but also highlighted actionable pathway targets to mitigate toxicity. These findings demonstrate that metabolomics provides a functional, pathway-level understanding of safety and patient response, which is crucial for enhancing cell therapy design, monitoring strategies, and clinical outcomes.
Using Metabolon’s high-resolution metabolomics platform, researchers identified clear and reproducible metabolic signatures that distinguished patients who developed high-grade NEs (grade ≥ 3). Notable findings include:
- Elevated Tryptophan Breakdown Signals Higher Neurotoxicity Risk – Patients who developed severe neurological events consistently showed higher breakdown of tryptophan, leading to increased levels of metabolites, such as quinolinate. These markers were present both before and after treatment and are strongly associated with heightened neurotoxicity risk.
- Increased Arginine Pathway Activity Reflects Heightened Immune Stress – Severe cases also showed a shift in how the body processes arginine, resulting in the production of more urea and acetylated polyamines, such as N1, N12-diacetylspermine. This pattern reflects increased immune system activation and may serve as another indicator of neurotoxicity risk.
- CSF Findings Confirm Metabolic Disruption in the Brain – Cerebrospinal fluid samples taken during neurotoxic events showed the same metabolic disruptions observed in blood—higher levels of glutamate and other stress-related metabolites—confirming that these changes directly involve the central nervous system.
- Metabolite-Based Scores Predict Neurotoxicity Better Than Traditional Markers – New metabolic pathway scores built from these biomarkers outperformed standard inflammatory markers (such as IL-6 and TNFα) in identifying patients at risk for severe neurological events. This demonstrates the potential for more accurate, metabolomics-driven early warning tools.
- Key Metabolites Also Track with Disease Progression – The same metabolites linked to neurotoxicity—such as quinolinate and acetylated polyamines—were also associated with worse disease outcomes. Machine-learning models reinforced the importance of the tryptophan-kynurenine pathway for neurotoxicity associated with CAR T cell therapy.
“These findings underscore the power of metabolomics to reveal mechanisms that are invisible to genomic, proteomic, and cellular assays alone,” said Ro Hastie, CEO of Metabolon. “By enabling unprecedented resolution into metabolic dysfunction associated with CAR T-cell therapy, Metabolon’s platform has helped identify new biomarkers and potential therapeutic targets to mitigate severe neurotoxicity.”
To learn more about Metabolon’s industry-leading Global Discovery Panel, please visit: https://www.metabolon.com/services/untargeted-metabolomics/global-panel/
