Neurological complications of cancer immunotherapy (CAR T cells)

Rubin, Daniel B.; Vaitkevicius, Henrikas

doi:10.1016/j.jns.2021.117405

Cited by 11 publications

(32 citation statements)

References 48 publications

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“…There is growing evidence suggesting that high levels of proinflammatory cytokines may produce endothelial activation with subsequent increased blood brain barrier permeability leading to cortical dysfunction such as a cortical spreading depression. 9 The presence of focal and generally reversible symptoms, the lack of structural findings on imaging, the absence of specific CSF findings, together with the focal slowing in the EEG exam, supports this hypothesis. 10 A central autonomic dysfunction leading to cardiovascular dysfunction has been described in epilepsy, multiple sclerosis, stroke and other neurological conditions.…”

mentioning

confidence: 83%

Neurotoxicity‐associated sinus bradycardia after chimeric antigen receptor T‐cell therapy

Català

Iacoboni

et al. 2022

Hematological Oncology

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The advent of chimeric antigen receptor (CAR) T-cell therapy has changed the therapeutic landscape of relapsed/refractory aggressive B-cell lymphomas. Cytokine release syndrome and immune effector cellassociated neurotoxicity syndrome (ICANS) are the typical adverse events associated with this therapy. Cardiovascular toxicities have also been reported in this setting. However, there is scarce data regarding the development of sinus bradycardia after CAR T-cell therapy. Here, we detail the clinical course of 4 patients with aggressive B-cell malignancies who received CAR T-cells and developed transient and reversible sinus bradycardia in the context of ICANS. We also discuss several hypotheses behind the pathophysiology of this potential new adverse event.

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mentioning

confidence: 83%

Neurotoxicity‐associated sinus bradycardia after chimeric antigen receptor T‐cell therapy

Català

Iacoboni

et al. 2022

Hematological Oncology

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“…deren Aggravation führen können, sind z. B. Temozolomid, Procarbazin, Vincristin, Lomustin, Bevacizumab, Marizomib und „Chimeric-antigen-receptor“(CAR)-T-Zellen [ 3 ].…”

Section: Hintergrundunclassified

“… Die ZNS(Zentralnervensystem)-Toxizität nach Behandlung mit CAR-T-Zellen muss sehr genau diagnostisch eingeordnet werden, ggf. ist eine Therapie mit Tocilizumab, einem gegen den Interleukin-6-Rezeptor gerichteten Antikörper, einzusetzen [ 3 ]. …”

Section: Systematisches Klinisches Und Diagnostisches Vorgehenunclassified

Tumortherapieassoziierte neurologische Symptome

2021

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ZusammenfassungDie onkologische Behandlung ist biomarkerbasierter, molekular maßgeschneiderter und effektiver geworden. Aufbauend auf der zunehmenden Entschlüsselung zellbiologischer und molekularer Mechanismen steigt auch die Zahl zielgerichteter medikamentöser Therapien. Es steigt zudem die Zahl der Langzeitüberlebenden. Eine neuro(onko)logische Betreuung wird immer wichtiger, nicht nur wegen vermehrter direkter tumorbedingter Symptome – wie etwa der höheren Inzidenz einer Metastasierung in das Zentralnervensystem –, sondern weil im Zuge dieser modernen onkologischen systemischen Therapieformen ein breites Spektrum therapieassoziierter neurologischer Symptome auftritt, die einer sorgfältigen und raschen neurologischen/neuroonkologischen Evaluation und Therapiekonzeption bedürfen. Das Ziel dieses Artikels ist es, das Bewusstsein für die häufigsten therapieassoziierten neurologischen Symptome zu schärfen.

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“…Other inflammatory markers, such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin, have been associated with increased ICANS severity, but lack specificity for ICANS because they are also elevated in CRS 9 , 14 . Neuroimaging, such as CT and MRI scans, do not typically reveal abnormalities with the exception of severe ICANS resulting in cerebral edema 22 , 23 . Multivariable models have been effective in assessing the overall risk of ICANS, but do not account for continuous changes in the grade of ICANS on the order of hours 24 , 25 .…”

Section: Introductionmentioning

confidence: 99%

EEG-based grading of immune effector cell-associated neurotoxicity syndrome

Jones

Eckhardt

Sun

et al. 2022

Sci Rep

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CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47–0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.

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Neurological complications of cancer immunotherapy (CAR T cells)

Cited by 11 publications

References 48 publications

Neurotoxicity‐associated sinus bradycardia after chimeric antigen receptor T‐cell therapy

Neurotoxicity‐associated sinus bradycardia after chimeric antigen receptor T‐cell therapy

Tumortherapieassoziierte neurologische Symptome

EEG-based grading of immune effector cell-associated neurotoxicity syndrome

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