Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 28;8(10):2491-2498.
doi: 10.1182/bloodadvances.2023011669.

Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity

Matteo Mauget  1   2 , Sophie Lemercier  3 , Quentin Quelven  2 , Adel Maamar  2 , Faustine Lhomme  1 , Sophie De Guibert  1 , Roch Houot  1   4 , Guillaume Manson  1
Affiliations

Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity

Matteo Mauget et al. Blood Adv. .

Abstract

International guidelines regarding the management of immune effector cell-associated neurotoxicity syndrome (ICANS) recommend several diagnostic investigations, including magnetic resonance imaging (MRI), lumbar puncture (LP), and electroencephalogram (EEG) based on ICANS grade. However, the impact of these investigations has not yet been evaluated. Here, we aimed to describe the role of MRI, LP, and EEG in the management of ICANS in a cohort of real-life patients treated with chimeric antigen receptor (CAR) T cells at the University Hospital of Rennes, France. Between August 2018 and January 2023, a total of 190 consecutive patients were treated with CAR T cells. Among those, 91 (48%) developed ICANS. MRI was performed in 71 patients (78%) with ICANS, with a therapeutic impact in 4% of patients, despite frequent abnormal findings. LP was performed in 43 patients (47%), which led to preemptive antimicrobial agents in 7% of patients, although no infection was eventually detected. Systematic EEG was performed in 51 patients (56%), which led to therapeutic modifications in 16% of patients. Our study shows that EEG is the diagnostic investigation with the greatest therapeutic impact, whereas MRI and LP appear to have a limited therapeutic impact. Our results emphasize the role of EEG in the current guidelines but question the need for systematic MRI and LP, which might be left to the discretion of the treating physician.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest disclosure: R.H. reports honoraria from Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda, and Roche; and consultancy at Kite/Gilead, Novartis, Bristol Myers Squibb/Celgene, ADC Therapeutics, Incyte, and Miltenyi. G.M. reports honoraria from Bristol Myers Squibb/Celgene, Gilead-Kite, and Takeda. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Diagnostic investigation strategies (n = 91). EEG, Electroencephalogram; LP, Lumbar puncture; MRI, Magnetic resonance imaging.
Figure 2.
Figure 2.
Therapeutic modifications due to investigations. EEG, Electroencephalogram; LP, Lumbar puncture; MRI, Magnetic resonance imaging.
See this image and copyright information in PMC

References

    1. Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25(4):625–638. - PubMed
    1. Schmidts A, Wehrli M, Maus MV. Toward better understanding and management of CAR-T cell-associated toxicity. Annu Rev Med. 2021;72:365–382. - PubMed
    1. Belin C, Devic P, Ayrignac X, et al. Description of neurotoxicity in a series of patients treated with CAR T-cell therapy. Sci Rep. 2020;10(1) - PMC - PubMed
    1. Lowe KL, Mackall CL, Norry E, Amado R, Jakobsen BK, Binder G. Fludarabine and neurotoxicity in engineered T-cell therapy. Gene Ther. 2018;25(3):176–191. - PubMed
    1. Hunter BD, Jacobson CA. CAR T-cell associated neurotoxicity: mechanisms, clinicopathologic correlates, and future directions. J Natl Cancer Inst. 2019;111(7):646–654. - PubMed

Substances