Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Objective quantification of pre-CAR-T EEG abnormalities for ICANS prognosis: insights from GTE scoring

Bone Marrow Transplantation volume 60, pages 1076–1078 (2025)Cite this article

Subjects

Access through your institution
Buy or subscribe

CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is an effective treatment for relapsed or refractory B-cell lymphoma but is associated with adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) [1]. While CRS is well understood as a cytokine-driven phenomenon, the pathogenesis of ICANS remains unclear, posing challenges for risk stratification and management [2, 3]. Identifying prognostic biomarkers is crucial for early intervention.

Various host-related factors (age, vascular status), therapy-related (CAR-T product type), and inflammatory (IL-1, IL-6) factors have been linked to ICANS risk [3]. Recent studies suggest that electroencephalography (EEG), a non-invasive tool for assessing brain activity, could help diagnose ICANS and assess its severity [4, 5]. Specifically, pre-CAR-T EEG abnormalities have been proposed as potential ICANS risk factors [6, 7].

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Higher GTE scores are associated with an increased incidence and severity of ICANS.

Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

References

  1. Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood. 2016;127:3312–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Morris EC, Neelapu SS, Giavridis T, Sadelain M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol. 2022;22:85–96.

    Article  CAS  PubMed  Google Scholar 

  3. Butt OH, Zhou AY, Ances BM, DiPersio JF, Ghobadi A. A systematic framework for predictive biomarkers in immune effector cell-associated neurotoxicity syndrome. Front Neurol. 2023;14:1110647. https://doi.org/10.3389/fneur.2023.1110647.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mauget M, Lemercier S, Quelven Q, Maamar A, Lhomme F, De Guibert S, et al. Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity. Blood Adv. 2024;8:2491–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jones DK, Eckhardt CA, Sun H, Tesh RA, Malik P, Quadri S, et al. EEG-based grading of immune effector cell-associated neurotoxicity syndrome. Sci Rep. 2022;12:20011. https://doi.org/10.1038/s41598-022-24010-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pensato U, Amore G, Muccioli L, Sammali S, Rondelli F, Rinaldi R, et al. CAR t-cell therapy in BOlogNa-NEUrotoxicity TReatment and Assessment in Lymphoma (CARBON-NEUTRAL): proposed protocol and results from an Italian study. J Neurol. 2023;270:2659–73.

    Article  CAS  PubMed  Google Scholar 

  7. Hernani R, Aiko M, Victorio R, Benzaquén A, Pérez A, Piñana JL, et al. EEG before chimeric antigen receptor T-cell therapy and early after onset of immune effector cell-associated neurotoxicity syndrome. Clin Neurophysiol. 2024;163:132–42.

    Article  PubMed  Google Scholar 

  8. Barcelon EA, Mukaino T, Yokoyama J, Uehara T, Ogata K, Kira JI, et al. Grand Total EEG Score Can Differentiate Parkinson’s Disease From Parkinson-Related Disorders. Front Neurol. 2019;10:398. https://doi.org/10.3389/fneur.2019.00398.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Claus JJ, Strijers RL, Jonkman EJ, Ongerboer de Visser BW, Jonker C, Walstra GJ, et al. The diagnostic value of electroencephalography in mild senile Alzheimer’s disease. Clin Neurophysiol. 1999;110:825–32.

    Article  CAS  PubMed  Google Scholar 

  10. Möhn N, Bonda V, Grote-Levi L, Panagiota V, Fröhlich T, Schultze-Florey C, et al. Neurological management and work-up of neurotoxicity associated with CAR T cell therapy. Neurol Res Pr. 2022;4:1. https://doi.org/10.1186/s42466-021-00166-5.

    Article  Google Scholar 

  11. Schoeberl F, Tiedt S, Schmitt A, Blumenberg V, Karschnia P, Burbano VG, et al. Neurofilament light chain serum levels correlate with the severity of neurotoxicity after CAR T-cell treatment. Blood Adv. 2022;6:3022–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We acknowledge the technical staff at the Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, for the EEG test. We also thank the ward and transfusion center staff for supporting CAR-T cell therapy.

Author information

Author notes

  1. These authors contributed equally: Hidetaka Nakagaki, Takuji Yamauchi

Authors and Affiliations

  1. Department of Hematology, Oncology & Cardiovascular Medicine, Kyushu University Hospital, Fukuoka, 812-8582, Japan

    Hidetaka Nakagaki, Takuji Yamauchi, Daisuke Ishihara, Hiroshi Imanaga, Kensuke Sasaki, Teppei Sakoda, Fumiaki Jinnouchi, Kohta Miyawaki, Takahiro Shima, Yoshikane Kikushige, Yasuo Mori, Koichi Akashi & Koji Kato

  2. Department of Neurology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Takahiko Mukaino, Mitsuru Watanabe, Hiroshi Shigeto & Noriko Isobe

  3. Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Hospital, Fukuoka, 812-8582, Japan

    Ayumi Sakata, Eriko Watanabe, Taeko Hotta & Yuya Kunisaki

  4. Division of Medical Technology, Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Ayumi Sakata & Hiroshi Shigeto

Authors
  1. Hidetaka Nakagaki
    View author publications

    Search author on:PubMed Google Scholar

  2. Takuji Yamauchi
    View author publications

    Search author on:PubMed Google Scholar

  3. Takahiko Mukaino
    View author publications

    Search author on:PubMed Google Scholar

  4. Ayumi Sakata
    View author publications

    Search author on:PubMed Google Scholar

  5. Eriko Watanabe
    View author publications

    Search author on:PubMed Google Scholar

  6. Mitsuru Watanabe
    View author publications

    Search author on:PubMed Google Scholar

  7. Daisuke Ishihara
    View author publications

    Search author on:PubMed Google Scholar

  8. Hiroshi Imanaga
    View author publications

    Search author on:PubMed Google Scholar

  9. Kensuke Sasaki
    View author publications

    Search author on:PubMed Google Scholar

  10. Teppei Sakoda
    View author publications

    Search author on:PubMed Google Scholar

  11. Fumiaki Jinnouchi
    View author publications

    Search author on:PubMed Google Scholar

  12. Kohta Miyawaki
    View author publications

    Search author on:PubMed Google Scholar

  13. Takahiro Shima
    View author publications

    Search author on:PubMed Google Scholar

  14. Yoshikane Kikushige
    View author publications

    Search author on:PubMed Google Scholar

  15. Yasuo Mori
    View author publications

    Search author on:PubMed Google Scholar

  16. Taeko Hotta
    View author publications

    Search author on:PubMed Google Scholar

  17. Yuya Kunisaki
    View author publications

    Search author on:PubMed Google Scholar

  18. Hiroshi Shigeto
    View author publications

    Search author on:PubMed Google Scholar

  19. Noriko Isobe
    View author publications

    Search author on:PubMed Google Scholar

  20. Koichi Akashi
    View author publications

    Search author on:PubMed Google Scholar

  21. Koji Kato
    View author publications

    Search author on:PubMed Google Scholar

Contributions

HN, TY, DI, HI, KS, TS, FJ, KM, TS, YK, YM, and KK performed CAR-T cell therapy and were involved in the clinical care of the patients. AS, EW, TH, and YK conducted the EEG tests. TM, MW, and HS analyzed the EEGs and calculated the GTE scores. HN, TY, NI, KA, and KK wrote the manuscript with help from all authors.

Corresponding author

Correspondence to Koji Kato.

Ethics declarations

Competing interests

KK; Honoraria: AbbVie, Bristol-Myers Squibb, Chugai, Dainippon-Sumitomo, Janssen, Kyowa Kirin, MSD, AbbVie, Ono, Gilead Sciences, Novartis; Consulting or Advisory Role: AbbVie, AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Janssen, Bristol-Myers Squibb, Novartis, Gilead Sciences; Research Funding: AbbVie, Astellas, MSD, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Janssen, Kyowa Kirin, Novartis, Ono, Gilead Sciences.

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Kyushu University. All methods were performed in accordance with the relevant guidelines and regulations. Informed consent was obtained from all participants.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakagaki, H., Yamauchi, T., Mukaino, T. et al. Objective quantification of pre-CAR-T EEG abnormalities for ICANS prognosis: insights from GTE scoring. Bone Marrow Transplant 60, 1076–1078 (2025). https://doi.org/10.1038/s41409-025-02616-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-025-02616-z

Search

Advanced search

Quick links