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Metabolomics-derived pathway scores outperform inflammatory protein markers, providing risk prediction where proteomics fails
MORRISVILLE, North Carolina, February 17, 2026 /PRNewswire/ — MetabolismInc., the global leader in providing metabolomics solutions advancing a wide variety of life science research, diagnostics, therapeutic development and precision medicine applications, today announced that its cutting-edge global metabolomics platform has been used by researchers at Kite, a Gilead company, for the broadest metabolomic study Leveraging Metabolon’s global untargeted discovery panel, Kite researchers analyzed more than 3,800 longitudinal serum and plasma samples, as well as 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, allowed researchers to discover metabolic pathways strongly associated with serious neurological events (NE), significant and sometimes fatal toxicity of CAR-T cell therapy. Despite the transformative efficacy of CAR T cell therapies 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 underlying CAR T cell-associated neurotoxicity, information that is not accessible solely through proteomics or cytokine profiling,” said Heino Heyman, Director of Global Field Metabolomics Sciences at Metabolon. “By mapping disruptions in tryptophan catabolism, NMDA-related excitotoxicity, and polyamine metabolism, the analysis not only identified patients at risk for serious neurological events, but also highlighted actionable pathway targets to mitigate toxicity.
Using Metabolon’s high-resolution metabolomics platform, researchers identified clear and reproducible metabolic signatures that distinguished patients who developed high-grade EN (grade ≥ 3). Notable results include:
- High tryptophan degradation signals higher neurotoxicity risk – Patients who developed serious neurological events consistently showed higher tryptophan breakdown, leading to increased levels of metabolites, such as quinolinate. These markers were present before and after treatment and are strongly associated with an increased risk of neurotoxicity.
- Increased arginine pathway activity reflects increased immune stress – Severe cases also showed a change in the way the body processes arginine, leading to the production of more urea and acetylated polyamines, such as N1, N12-diacetylspermine. This pattern reflects increased activation of the immune system and may serve as another indicator of neurotoxicity risk.
- CSF results confirm metabolic disturbance in the brain – Cerebrospinal fluid samples taken during neurotoxic events showed the same metabolic disturbances observed in the 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 constructed from these biomarkers outperformed standard inflammatory markers (such as IL-6 and TNFα) in identifying patients at risk for serious neurological events. This demonstrates the potential for more accurate, metabolomics-based early warning tools.
- Key metabolites also track disease progression – The same metabolites linked to neurotoxicity, such as quinolinate and acetylated polyamines, were also associated with worse disease outcomes. Machine learning models have reinforced the importance of the tryptophan-kynurenine pathway for neurotoxicity associated with CAR T cell therapy.
“These results highlight the power of metabolomics to reveal mechanisms invisible to genomic, proteomic and cellular assays alone,” said Ro Hastie, CEO of Metabolon. “By enabling unprecedented resolution of metabolic dysfunction associated with CAR T cell therapy, Metabolon’s platform has helped identify novel biomarkers and potential therapeutic targets to alleviate severe neurotoxicity.
To learn more about Metabolon’s industry-leading global discovery panel, please visit: https://www.metabolon.com/services/untargeted-metabolomics/global-panel/
About Metabolon
MetabolismInc. is the global leader in metabolomics, with a mission to provide biochemical data and insights that expand and accelerate the impact of life sciences research and complement other “omics” technologies. With 25 years of experience, more than 15,000 customer projects, more than 4,000 scientific publication references and ISO 9001: 2015, CLIA and CAP certifications, Metabolon has developed cutting-edge scientific, technological and bioinformatics techniques. Metabolon’s Global Discovery Panel is powered by the world’s largest proprietary metabolomics reference library. Metabolon’s industry-leading expertise in data and translational science helps its customers and partners answer some of the hardest and most pressing questions in life sciences, accelerating research and improving development success. The company offers scalable and customizable multiomics solutions, including metabolomics and lipidomics, that meet customer needs from discovery through clinical trials and product lifecycle management. For more information, please visit www.metabolon.com and follow us LinkedIn And Twitter.
About metabolomics
Metabolomics, the large-scale study of all small molecules in a biological system, is the only omics technology that provides a complete functional readout of the current state of a biological system. Metabolomics allows researchers to see beyond the genetic variation of individuals, capturing the combined impact of genetic and environmental factors, including the effects of medications, diet, lifestyle and the microbiome, on human health. By measuring thousands of discrete chemical signals that form biological pathways in the body, metabolomics can reveal important biomarkers, enabling a better understanding of a drug’s mechanism of action, pharmacodynamics and safety profile, as well as individual responses to treatment.
SOURCE Metabolon, Inc.
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Source: PR Newswire
