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
. 2021 Sep 1;23(9):1569-1575.
doi: 10.1093/neuonc/noab077.

Evaluation of mid-term (6-12 months) neurotoxicity in B-cell lymphoma patients treated with CAR T cells: a prospective cohort study

Didier Maillet  1 , Catherine Belin  1 , Christine Moroni  2 , Stefania Cuzzubbo  1 , Renata Ursu  1 , Lila Sirven-Villaros  1   3 , Roberta Di Blasi  3   4 , Catherine Thieblemont  3   4 , Antoine F Carpentier  1   3
Affiliations

Evaluation of mid-term (6-12 months) neurotoxicity in B-cell lymphoma patients treated with CAR T cells: a prospective cohort study

Didier Maillet et al. Neuro Oncol. .

Abstract

Background: Chimeric antigen receptor-modified T (CAR T) cells are profoundly changing the standard of care in B-cell malignancies. This new therapeutic class induces a significant number of acute neurotoxicity, but data regarding mid- and long-term neurological safety are scarce. We evaluated mid-term neurological safety, with special emphasis on cognitive functions, in a series of adults treated with CAR T cells.

Methods: Patients treated in a single center with CD19-targeted CAR T cells for a relapsing B-cell lymphoma were prospectively followed up by neurologists. Before CAR T-cell infusion, all patients underwent neurological examinations with neuropsychological testing and filled out questionnaires assessing anxiety, depression, and cognitive complaints. Patients surviving without tumor progression were re-evaluated similarly, 6-12 months later.

Results: In this prospective cohort of 56 consecutive adult patients treated with CAR T cells, 27 were eligible for mid-term evaluation (median time 7.6 months). Twelve patients developed an acute and reversible neurotoxicity with median duration time of 5.5 days. In all patients, neurological examination on mid-term evaluation was similar to baseline. In self-assessment questionnaires, 63% of patients reported clinically meaningful anxiety, depression, or cognitive difficulties at baseline, a number reduced to 44% at the time of mid-term evaluation. On cognitive assessments, no significant deterioration was found when compared to baseline, in any cognitive functions assessed (verbal and visual memory, executive functions, language, and praxis), even in patients who developed acute neurotoxicity.

Conclusion: In this cohort of patients treated with CD19-targeted CAR T cells, we found no evidence for neurological or cognitive toxicity, 6-12 months after treatment.

Keywords: B-cell lymphoma; CAR T cells; axicabtagene ciloleucel; brain; immune effector cell-associated neurotoxicity syndrome; lymphoma; nervous system; neurotoxicity; tisagenlecleucel; toxicity.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flowchart of the patients analyzed in the study.
See this image and copyright information in PMC

References

    1. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531–2544. - PMC - PubMed
    1. Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;377: 45–56. - PubMed
    1. Topp MS, Gökbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66. - PubMed
    1. Gust J, Hay KA, Hanafi LA, et al. Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov. 2017;7(12):1404–1419. - PMC - PubMed
    1. Santomasso BD, Park JH, Salloum D, et al. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov. 2018;8(8):958–971. - PMC - PubMed

Publication types