Neurological Effects of CAR-T therapy

A research team at Brigham and Women’s Hospital recently catalogued the neurological symptoms of patients administered chimeric antigen receptor (CAR) T-cell therapy in order to better understand its neurotoxic adverse effects.

CAR T-cell therapy is known to train and strengthen a patient’s immune system to attack tumors. Early successes in clinical trials have led to approvals of the therapy for the treatment of recurrent blood cancers, including leukemia and lymphoma. However, despite recent successes, CAR T-cell therapy carries the risk of severe adverse effects such as neurotoxicity, which can result in headache, confusion, and delirium. These effects are poorly understood and categorized, according to the researchers.

The observational cohort study, published in the Brain, consisted of 100 lymphoma patients admitted to the Dana-Farber/Brigham and Women’s Cancer Center for CAR T-cell therapy infusion through 2 months post-infusion. All diagnostic assessments, such as laboratory tests and imaging scans, were reviewed, according to the press release.

"We shared a few clinical cases early in the therapies which were very severe and unusual from a neurological standpoint," senior author Henrikas Vaitkevicius, MD, of the Department of Neurology, said in the release. "This sparked an interest to collaborate with oncology and T-cell therapy groups and allowed us to evaluate the majority of patients prospectively rather than retrospectively."

Among the most prevalent symptoms associated with CAR T-cell therapy is encephalopathy, a brain disease that causes confusion, with added symptoms of headache, tremor, weakness, and language dysfunction. Many of these effects were reversible and symptoms almost always resolved over time, according to the study. The authorse said these findings prove the widespread neurological effects found in patients after CAR T-cell therapy.

The authors also noted that these neurological deficits associated with CAR T-cell therapy originated from areas that appeared to be metabolically silent, implying that clinical assessment of neurotoxicity and the use of imaging are important.

Investigators are now building and validating a model for more accurate scoring and diagnosis of CAR T-associated neurotoxicity.