28 May 2019

A US study has outlined the neurotoxic side effects of chimeric antigen receptor T-cell therapy.

CAR T-cell therapy has been hailed as a medical breakthrough, with several treatments approved in the UK for recurrent blood cancers. Nevertheless, there is a risk of severe side effects, including neurotoxicity, which can result in headache, confusion, and delirium, among other neural changes. However, to date the extent of neurotoxic side-effects of CAR T-cell therapy has been poorly understood.

A team at Brigham and Women's Hospital in Boston, USA, catalogued the neurological symptoms of 100 patients who had received CAR T-cell therapy. They found that while 77% of patients experienced at least one neurological symptom, the effects were temporary.

The team, led by Dr Henrikas Vaitkevicius of the Department of Neurology at the Brigham, conducted an observational cohort study of 100 patients admitted to the Dana-Farber/Brigham and Women's Cancer Center for CAR T-cell therapy between 2015 and 2018. The patients had a range of cancers, including lymphoma (74%), multiple myeloma (14%), leukaemia (10%), and sarcoma (2%).

They evaluated symptoms from the start of CAR T-cell therapy infusion until two months after treatment ceased. They also studied all diagnostic assessments, including laboratory tests and imaging scans.

Publishing their results in in journal Brain, they found that the most common symptom was encephalopathy, while headache, tremor, weakness and language dysfunction were also observed. Importantly, most of these side effects were reversible, and symptoms almost always resolved over time.

The research team also discovered that the neurological deficits associated with CAR T-cell therapy often originate from areas of the brain which appeared to be metabolically silent. They say that this has implications for the clinical assessment of neurotoxicity, with EEG and PET scans proving more useful for identifying neurologic dysfunction than MRI.

The team is now building and validating a model for more accurate scoring and diagnosis of CAR T-cell therapy-associated neurotoxicity.

Source: Rubin, D.B., Danish, H.H., Ali, A.B., Li, K., LaRose, S., Monk, A.D., Cote, D.J., Spendley, L., Kim, A.H., Robertson, M.S., Torre, M., Smith, T.R., Izzy, S., Jacobson, C.A., Lee, J.W., Vaitkevicius, H. (2019) “Neurological toxicities associated with chimeric antigen receptor T-cell therapy”, Brain, available from doi: 10.1093/brain/awz053


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