Chimeric Antigen Receptor T Cell-Related Neurotoxicity: Mechanisms, Clinical Presentation, and Approach to Treatment

TY - JOUR

T1 - Chimeric Antigen Receptor T Cell-Related Neurotoxicity

T2 - Mechanisms, Clinical Presentation, and Approach to Treatment

AU - Rice, Jessica

AU - Nagel, Sarah

AU - Randall, Julie

AU - Hinson, Holly

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Purpose of review: Chimeric antigen receptor T cell (CAR-T) adoptive cell therapy is an effective treatment for patients with refractory B cell malignancies. As its use has grown, there has been an increase in the incidence of a serious, potentially fatal neurotoxicity known as immune effector cell-associated neurotoxicity syndrome (ICANS). This review discusses the clinical manifestations of this neurotoxicity syndrome, current grading systems, management strategies, and proposed biologic mechanisms leading to neurotoxicity. Recent findings: Current research suggests that patients with a higher disease burden and higher CAR-T cell doses are positively associated with the development of ICANS, as are elevated serum levels of proinflammatory cytokines and the presence of cytokine release syndrome (CRS). While patterns observed on neuroimaging and electroencephalogram (EEG) are non-specific for the diagnosis of ICANS, each modality may provide helpful clinical information such as the detection of cerebral edema, the most serious of associated symptoms. Anti-epileptic medications and corticosteroids may ameliorate the symptoms of ICANS. Summary: The mechanism for ICANS is currently unknown; however, systemic inflammation and cytokine production triggering a cascade of endothelial activation and BBB disruption likely contribute. With limited treatment options available, further clinical research into the precise mechanism and treatment is urgently needed as the use of CAR-T and other adoptive cell therapies continues to grow.

AB - Purpose of review: Chimeric antigen receptor T cell (CAR-T) adoptive cell therapy is an effective treatment for patients with refractory B cell malignancies. As its use has grown, there has been an increase in the incidence of a serious, potentially fatal neurotoxicity known as immune effector cell-associated neurotoxicity syndrome (ICANS). This review discusses the clinical manifestations of this neurotoxicity syndrome, current grading systems, management strategies, and proposed biologic mechanisms leading to neurotoxicity. Recent findings: Current research suggests that patients with a higher disease burden and higher CAR-T cell doses are positively associated with the development of ICANS, as are elevated serum levels of proinflammatory cytokines and the presence of cytokine release syndrome (CRS). While patterns observed on neuroimaging and electroencephalogram (EEG) are non-specific for the diagnosis of ICANS, each modality may provide helpful clinical information such as the detection of cerebral edema, the most serious of associated symptoms. Anti-epileptic medications and corticosteroids may ameliorate the symptoms of ICANS. Summary: The mechanism for ICANS is currently unknown; however, systemic inflammation and cytokine production triggering a cascade of endothelial activation and BBB disruption likely contribute. With limited treatment options available, further clinical research into the precise mechanism and treatment is urgently needed as the use of CAR-T and other adoptive cell therapies continues to grow.

KW - Adoptive cell transfer

KW - Blood-brain barrier

KW - Cerebral edema

KW - Chimeric antigen receptor T cell

KW - Immune effector cell-associated neurotoxicity syndrome

UR - http://www.scopus.com/inward/record.url?scp=85069447782&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069447782&partnerID=8YFLogxK

U2 - 10.1007/s11940-019-0580-3

DO - 10.1007/s11940-019-0580-3

M3 - Review article

AN - SCOPUS:85069447782

VL - 21

JO - Current Treatment Options in Neurology

JF - Current Treatment Options in Neurology

SN - 1092-8480

IS - 8

M1 - 40

ER -