Neurologists evaluate neurological symptoms with CAR T-cell therapy

By Michael Woodhead

16 May 2019

Chimeric antigen receptor (CAR) T-cell therapy for blood cancers has numerous poorly-characterised neurologic adverse effects, a new US study shows.

A complex pattern of neurotoxicity that can result in headache, confusion, and delirium, is seen in 77% of patients undergoing the novel immunotherapy, according to neurologists and oncologists at Brigham and Women’s Hospital.

They evaluated neurological toxicity in a consecutive series of 100 patients up to two months after CAR T-cell therapy, for treatment of cancers such as  lymphoma (74%), myeloma (14%), leukaemia (10%), and sarcoma (2%). The median age of the cohort was 65 years old and 39% of patients were female.

The most commonly occurring neurological symptoms were encephalopathy (57%), headache (42%), tremor (38%), aphasia (35%) and focal weakness (11%).

Most of these effects were reversible, and symptoms almost always resolved over time, the study authors noted  in the article published in Brain.

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

The researchers also noted a unique pattern of activity, or inactivity, in their study. The neurological deficits associated with therapy often originated from areas which appeared 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,” said lead author and neurologist Dr Daniel 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.

“As this form of treatment is more widely adopted, recognition of the frequently encountered symptoms will be of increasing importance for the neurologists and oncologists caring for this growing patient population,” the study authors concluded.

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