Blood cancers

Tool can predict CAR T-cell therapy neurotoxicity

A simple tool has been developed to predict the delayed neurotoxicity that occurs in about half of patients who undergo CAR T-cell therapy.

The score  – based on readily available clinical and laboratory measures – will allow observation and treatment to be targeted at those most at risk, allowing low risk patients to be discharged from hospital sooner after treatment, according to US clinicians.

Writing in JAMA Neurology, doctors at Brigham and Women’s Hospital say that neurotoxicity is one of the two main adverse effects of CAR T-cell therapy, but generally occurs after about a week, in contrast to the cytokine release syndrome (CRS) that occurs soon after infusion.

Neurotoxicity can present as encephalopathy, aphasia, focal weakness, numbness, apraxia, seizures, or in rare cases, fulminant cerebral oedema and death, they write. And because of its unpredictability, many centres that offer CAR T-cell therapy currently keep all patients hospitalised for seven to 14 days to observe for neurologic symptoms.

The clinicians note that previous studies have shown that neurotoxicity is associated with factors such as higher serum levels of C-reactive protein (CRP), higher levels of the inflammatory cytokine IL-6 and serum ferritin levels, and also associated with early CRS and the use of tocilizumab to treat it.

They further investigated prognostic factors in a cohort of  204 adults receiving axicabtagene ciloleucel for relapsed or refractory lymphoma, of whom 58% subsequently developed neurotoxicity.

They identified nine factors on which to base a prognostic score: age, aggressive histologic subtype, fever, CRP, ferritin, WBC count, dose of tocilizumab and timing and severity of CRS.

When tested in an inner validation cohort comprising 45 patients, the score predicted neurotoxicity with an area under the curve (AUC) of 74%, a sensitivity of 82% and a specificity of 70%.

The study investigators said an advantage of their score is that it can be calculated from data that is readily available during the first few days of admission.

“This allows high-risk patients to be appropriately triaged to higher levels of care, where early symptoms of neurotoxicity can be more rapidly recognized and the resources necessary to monitor and treat are more readily available,” they wrote.

And as the use of CAR T-cell therapy becomes more widespread, the tool may also allow many patients to avoid unnecessary prolonged hospital stays,” they suggested.

“Similarly, patients who are unlikely to develop neurotoxicity may potentially be discharged earlier from the hospital, obviating the risks that accompany prolonged hospitalization and conserving substantial resources,” they concluded.

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