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


Authors: Raj, S. S.; Fei, T.; Fried, S.; Ip, A.; Fein, J. A.; Leslie, L. A.; Alarcon Tomas, A.; Leithner, D.; Peled, J. U.; Corona, M.; Dahi, P. B.; Danylesko, I.; Epstein-Peterson, Z.; Funnell, T.; Giralt, S. A.; Jacoby, E.; Kedmi, M.; Landego, I.; Lin, R. J.; Parascondola, A.; Pascual, L.; Orozco, N.; Park, J. H.; Palomba, M. L.; Salles, G.; Saldia, A.; Schöder, H.; Sdayoor, I.; Shah, G. L.; Scordo, M.; Shem-Tov, N.; Shimoni, A.; Slingerland, J.; Yerushalmi, R.; Nagler, A.; Greenbaum, B. D.; Vickers, A. J.; Suh, H. C.; Avigdor, A.; Perales, M. A.; van den Brink, M. R. M.; Shouval, R.
Article Title: An inflammatory biomarker signature of response to CAR-T cell therapy in non-Hodgkin lymphoma
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. © The Author(s) 2025.
Journal Title: Nature Medicine
Volume: 31
Issue: 4
ISSN: 1078-8956
Publisher: Nature Publishing Group  
Date Published: 2025-04-01
Start Page: 1183
End Page: 1194
Language: English
DOI: 10.1038/s41591-025-03532-x
PUBMED: 40169864
PROVIDER: scopus
PMCID: PMC12003198
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Roni Shouval -- Source: Scopus
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MSK Authors
  1. Maria Lia Palomba
    440 Palomba
  2. Sergio Andres Giralt
    1064 Giralt
  3. Heiko Schoder
    550 Schoder
  4. Jae Hong Park
    371 Park
  5. Andrew J Vickers
    887 Vickers
  6. Miguel-Angel Perales
    935 Perales
  7. Michael Scordo
    380 Scordo
  8. Gunjan Lalitchandra Shah
    438 Shah
  9. Catherine Amethyst Saldia
    26 Saldia
  10. Sandeep Sunder Raj
    23 Raj
  11. Richard Jirui Lin
    128 Lin
  12. Roni Shouval
    167 Shouval
  13. Gilles Andre Salles
    299 Salles
  14. Teng Fei
    45 Fei
  15. Ivan Patrick Landego
    21 Landego
  16. Joshua Alexaner Fein
    2 Fein