Neurologic Complications of Chimeric Antigen Receptor Therapy

Remarkable progress has been made with the availability of chimeric antigen receptor (CAR) T-cell products for treating refractory tumors. Neurotoxicity associated with these products is called immune effector cell associated neurotoxicity. Neurologic manifestations recognized with these products range from the more common encephalopathy, seizures, to the very rare cerebral edema. Encephalopathy is graded using Immune Effector Cell-Associated Encephalopathy grading score. Diagnosis, clinical grading, ancillary tools of neurologic assessment (computed tomography, magnetic resonance imaging, electroencephalogram, fundus examination, transcranial Doppler ultrasound, positron emission tomography), and treatment paradigms have improved, leading to better outcomes. Recognition of the common clinical presentations of CAR T-cell product neurotoxicity leads to early intervention, prevents worsening to higher grades, and helps identify any unique toxicities to a given product. Solid tumor antigen target CAR T-cell products in trials have shown much fewer instances of neurotoxicity compared to the current approved hematologic tumor products for refractory leukemia and lymphoma. Common underlying mechanisms for neurotoxicity is the triggered cytokine storm and engagement of the proliferating transfused CAR T-cells with patient’s tumor and host’s cells. Management of the neurotoxicity centers around use of glucocorticoids in most patients. Dosage and duration of steroids have been in a delicate balance among survival of CAR T-cells, mitigation of neurotoxicity, and limiting steroid toxicity in a very compromised patient. Newer ways of mitigating these toxicities with cytokine antagonists are being explored for prevention and treatment. Tremendous efforts by various investigators, clinicians, and nurses at the bedside have led to early recognition and early treatment, leading to better outcomes of this unique neurotoxicity.