An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma

Disease progression is a substantial challenge in patients with non-Hodgkin lymphoma (NHL) undergoing chimeric antigen receptor T cell (CAR-T) therapy. Here we present InflaMix (INFLAmmation MIXture Model), an unsupervised quantitative model integrating 14 pre-CAR-T infusion laboratory and cytokine measures capturing inflammation and end-organ function. Developed using a cohort of 149 patients with NHL, InflaMix revealed an inflammatory signature associated with a high risk of CAR-T treatment failure, including increased hazard of death or relapse (hazard ratio, 2.98; 95% confidence interval, 1.60-4.91; P < 0.001). Three independent cohorts comprising 688 patients with NHL from diverse treatment centers were used to validate our approach. InflaMix consistently and reproducibly identified patients with a higher likelihood of disease relapse and mortality, and it provided supplementary predictive value beyond established prognostic markers, including tumor burden. Moreover, InflaMix exhibited robust performance in cases with missing data, maintaining accuracy when considering only six readily available laboratory measures. These findings show that InflaMix is a valuable tool for point-of-care clinical decision-making in patients with NHL undergoing CAR-T therapy.

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Publication Details

Journal
Nature Medicine
Published
2025-04-01
DOI
https://doi.org/10.1038/s41591-025-03532-x
Citations
29
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
30.32
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An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma

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An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma

Marcel R.M. van den Brink, Ivetta Danylesko, Meirav Kedmi, Lori Ann Leslie, Heiko M. Schöder, Avichai Shimoni, Gunjan L. Shah, Richard J. Lin, Andrew Ip, Andrew Julian Vickers, Magdalena Corona, Inbal Sdayoor, Joshua Fein, Ivan Landego, Roni Shouval, L.C. Fernando Pascual, Jonathan U. Peled, Hyung C. Suh, Noga Shem‐Tov, Parastoo Bahrami Dahi, Michael Scordo, Doris Leithner, Shalev Fried, Amethyst Saldia, Maria Lia Palomba, Arnon Nagler, Zachary D. Epstein‐Peterson, Abraham Avigdor, Sandeep S. Raj, Benjamin D. Greenbaum, Allison Parascondola, Sergio A. Giralt, Ronit Yerushalmi, Miguel‐Angel Perales, Tyler Funnell, Gilles Salles, Elad Jacoby, John B. Slingerland, Ana Alarcón Tomás, Teng Fei, Jae H. Park, Natali Orozco
article en
29 citations

Abstract

Disease progression is a substantial challenge in patients with non-Hodgkin lymphoma (NHL) undergoing chimeric antigen receptor T cell (CAR-T) therapy. Here we present InflaMix (INFLAmmation MIXture Model), an unsupervised quantitative model integrating 14 pre-CAR-T infusion laboratory and cytokine measures capturing inflammation and end-organ function. Developed using a cohort of 149 patients with NHL, InflaMix revealed an inflammatory signature associated with a high risk of CAR-T treatment failure, including increased hazard of death or relapse (hazard ratio, 2.98; 95% confidence interval, 1.60-4.91; P < 0.001). Three independent cohorts comprising 688 patients with NHL from diverse treatment centers were used to validate our approach. InflaMix consistently and reproducibly identified patients with a higher likelihood of disease relapse and mortality, and it provided supplementary predictive value beyond established prognostic markers, including tumor burden. Moreover, InflaMix exhibited robust performance in cases with missing data, maintaining accuracy when considering only six readily available laboratory measures. These findings show that InflaMix is a valuable tool for point-of-care clinical decision-making in patients with NHL undergoing CAR-T therapy.

Nature MedicineVol. 31(4)
Hackensack University Medical Center (US), Memorial Sloan Kettering Cancer Center (US), Tel Aviv University (IL), Cornell University (US), Sheba Medical Center (IL), Hospital Universitario 12 De Octubre (ES), Hospital Universitario Puerta de Hierro Majadahonda (ES), City of Hope (US), Weill Cornell Medicine (US), Beckman Research Institute, University of Manitoba (CA)
Good health and well-being
Openalex Percentile: Top 0%
CAR-T cell therapy research
30.32
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