Neurological Side Effects of CAR T-Cell Therapy Revealed

By Lois Zoppi, B.A.May 16 2019

Researchers at Brigham and Women’s Hospital quantified the neurological symptoms associated with CAR T-cell therapy and found that 77 percent of patients receiving the treatment experienced at least one neurological side effect.

Shutterstock | Alpha Tauri 3D Graphics

CAR T-cell therapy, known in full as chimeric antigen receptor T-cell therapy, is a new immunotherapy treatment used for cancer that is developed to work according to a patient’s individual blood make up, meaning their cells can fight tumors with a personally cultivated treatment. The therapy involves reprogramming the patient’s immune cells so they can be used to target cancer.

The treatment lasts several weeks, with blood taken from the patient that is then ‘taught’ to fight cancer cells. The CAR-T blood is then given back to the patient so they can begin to fight the cancer cells in their body.

CAR T-cell therapy has been approved for use in the NHS against cases of relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) in patients up to the age of 25 that have not responded to other treatments. A second type of CAR T-cell therapy has been approved for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) as well.

Trials have shown that CAR T-cell therapy can cure some patients of cancer, but it is a complex treatment with risks attached.

Despite its success in early clinical trials, there are still risks of significant side effects from CAR T-cell therapy. Neurological changes are amongst the list of side effects, with neurotoxicity causing headaches, confusion, and delirium causing concern. The full range of side effects associated with CAR T-cell therapy has yet to be fully understood.

The researchers at Brigham and Women’s Hospital conducted a new study to catalogue the side effects experienced by patients using CAR T-cell therapy, in particular investigating rates of neurotoxicity. The study involved an observational cohort study including 100 lymphoma patients at the Dana-Farber/Brigham and Women’s Cancer Center for CAR T-cell therapy between 2015 and 2018.

Symptoms were monitored when patients began CAR T-cell therapy until two months after their last infusion of CAR T-cells. Imaging scans, lab tests, and diagnostic assessments were also reviewed as part of the study.

The mechanism underlying CAR T-cell-associated neurotoxicity is unknown and symptoms can be very hard to predict,”

Study’s lead author Daniel Rubin, MD, PhD, of the Department of Neurology at the Brigham and Women’s Hospital.

“We conducted this study to better define the specific neurologic symptoms experienced by patients after CAR T-cell therapy.”

Results produced by the study show that neurological side effects are common amongst patients undergoing CAR T-cell therapy. Encephalopathy, a name for a group of brain diseases and not the name for a specific condition in itself, was the side effect most commonly experienced.

Encephalopathy causes symptoms such as confusion, headaches, tremors, weakness, and difficulties with language. It is important to note that the majority of these side effects were not found to be permanent when connected to CAR T-cell therapy, and patients’ symptoms lessened or resolved over time.

Senior author Henrikas Vaitkevicius, MD, from the Department of Neurology, said:

“We shared a few clinical cases early in the therapies which were very severe and unusual from a neurological standpoint. 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.”

Another discovery found as a result of the study that is important when considering the neurotoxicity associated with CAR T-cell therapy is a pattern of inactivity in the brain. The neurological problems stemming from CAR T-cell therapy were often found to come from areas of the brain that were seemingly metabolically silent.

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

The next step in research calls for researchers to build a certified model capable of scoring and diagnosing CAR T-associated neurotoxicity more accurately.