Brigham and Women’s Hospital Study Neurological Side Effects of CAR T-cell Therapy

In the Future, Computers Could Facilitate Neurological Condition Monitoring and Diagnoses

Science Daily reported that Brigham and Women’s Hospital organized a team to catalog neurological symptoms of recent patient CAR T-cell therapy to better understand neurotoxic side effects. Of note, neurological symptoms were observed frequently (77% of patients report at least one symptom); they are temporary.

CAR T-cell therapy has fundamentally transformed the clinical treatment of cancer. Under the immunotherapy umbrella, CAR T-cell treatment trains and strengthens a patient’s own immune system to attack tumors. Recent clinical research has led to FDA approvals for recurrent blood cancers including leukemia and lymphoma.

New treatments made possible by CAR T-cell therapy opens up new risks—in some cases potentially severe ones—for side effects. Potential categories include neurotoxicity triggering everything from headaches to confusion to delirium among other neural changes. As reported by Science Daily, debilitating effects remain poorly understood and characterized.

The Brigham and Women’s Hospital team embarked on a research effort to categorize neurotoxic side effects. “The mechanism underlying CAR T-cell-associated neurotoxicity is unknown and symptoms can be very hard to predict,” said lead author Daniel Rubin, MD, PhD, of the Department of Neurology at the Brigham. “We conducted this study to better define the specific neurologic symptoms experienced by patients after CAR T-cell therapy.” To define clinical symptoms of CAR-T-associated neurotoxicity, the team conducted an observational cohort study of 100 lymphoma patients admitted to the Dana-Farber/Brigham and Women’s Cancer Center for CAR T-cell therapy between 2015 and 2018. The team evaluated symptoms from the start of CAR T-cell therapy infusion through two months’ post-infusion. In addition, all diagnostic assessments, including laboratory tests and imaging scans, were reviewed.

We shared a few clinical cases early in the therapies which were very severe and unusual from a neurological standpoint,” said senior author Henrikas Vaitkevicius, MD, of the Department of Neurology. “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.”

“Despite the common occurrence of neurologic symptoms, imaging studies such as MRI, which serve as a cornerstone of neurologic diagnosis, were almost always normal,” remarked Rubin. “In contrast, diagnostic studies that more directly evaluated neuronal functioning, like EEG and PET scan, could reliably detect and predict neurologic dysfunction.”

As a next step, investigators are building and validating a model for more accurate scoring and diagnosis of CAR T-associated neurotoxicity.

Lead Reserch/Investigator

Henrikas Vaitkevicius, MD, of the Department of Neurology.