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Evaluating the Patient with Neurotoxicity after Chimeric Antigen Receptor T-cell Therapy

  • Neuro-oncology (GJ Lesser, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Chimeric antigen receptor (CAR) T-cells are now a well-established treatment for hematologic malignancies. Their use in clinical practice has expanded quite rapidly and hospitals have developed CAR T-cell protocols to evaluate patients for associated toxicities, and particularly for neurotoxicity. There are many variables that influence the risk for developing this complication, many of which are not fully understood. The severity can be related to a particular product. Clinical vigilance is critical to facilitate early recognition of neurotoxicity, hence the importance of pre-CAR T-cell neurological evaluation of each patient. While details of such an evaluation may slightly differ between institutions, generally a comprehensive neurological evaluation including assessment of cognitive abilities along with magnetic resonance imaging (MRI) of the brain is a gold standard. Management of neurotoxicity requires a well-orchestrated team approach with specialists from oncology, neurology, oftentimes neurosurgery and neuro-intensive care. Diagnostic work-up frequently includes detailed neurologic evaluation with comparison to the baseline assessment, imaging of the brain, electroencephalogram, and lumbar puncture. While steroids are uniformly used for treatment, many patients also receive tocilizumab for an underlying and frequently concomitant cytokine release syndrome (CRS) in addition to symptom-driven supportive care. Novel CAR T-cell constructs and other agents allowing for potentially lower risk of toxicity are being explored. While neurotoxicity is predominantly an early, and reversible, event, a growing body of literature suggests that late neurotoxicity with variable clinical presentation can also occur.

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  1. Shannon P. Fortin Ensign and Charles Gaulin contributed equally to this work.

Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ, 85054, USA

    Shannon P. Fortin Ensign MD, PhD, Charles Gaulin MBBS, Januario Castro MD, Javier Munoz MD, MS, MBA & Allison Rosenthal DO

  2. Department of Neurosurgery and Neurology, University of Oklahoma, Norman, OK, USA

    Maya Hrachova DO

  3. Department of Neurology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN, 55905, USA

    Michael Ruff MD

  4. Department of Neurology, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ, 85054, USA

    Ehab Harahsheh MBBS & Maciej M. Mrugala MD, PhD, MPH

  5. Raymond G. Murphy VA Medical Center, 1501 San Pedro Drive SE, Albuquerque, NM, 87108, USA

    Kevin Vicenti MD, MS

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Dr. Fortin Ensign has nothing to disclose. Dr. Gaulin has nothing to disclose. Dr. Hrachova has nothing to disclose. Dr. Ruff has nothing to disclose. Dr. Harahsheh has nothing to disclose. Dr. Vicenti has nothing to disclose. Dr. Castro has nothing to disclose. Dr. Munoz reports personal fees from Pharmacyclics/Abbvie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Fosunkite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, Servier, Novartis, Morphosys/Incyte, Mei pharma, Zodiac, grants from Bayer, Gilead/Kite Pharma, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, other from Targeted Oncology, OncView, Curio, Kyowa, Physicians’ Education Resource, Dava, Global clinical insights, MJH, Shanghai Youyao, and Seattle Genetics, other from Gilead/Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche, during the conduct of the study. Dr. Rosenthal has nothing to disclose. Dr. Mrugala has nothing to disclose.

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Fortin Ensign, S.P., Gaulin, C., Hrachova, M. et al. Evaluating the Patient with Neurotoxicity after Chimeric Antigen Receptor T-cell Therapy. Curr. Treat. Options in Oncol. 23, 1845–1860 (2022). https://doi.org/10.1007/s11864-022-01035-2

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