CAR T-Cell Immunotherapy
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A team of French researchers has found that the use of magnetic resonance imaging (MRI) and lumbar puncture (LP) may not always be necessary as a diagnostic tool to help doctors manage serious neurotoxicity related to CAR T-cell therapy. The study, published today in the journal Blood Advances, further validated the use of noninvasive electroencephalogram (EEG) testing to measure electrical activity in the brain as sufficient to manage this condition.

“When treating patients for CAR T-cell associated toxicities, we typically follow pretty rigid guidelines based on phase one and two studies, and there is little to no clinical evidence to validate these,” said senior author Guillaume Manson, a hematologist at the University Hospital of Rennes in Rennes, France. “Some of these tests, like a lumbar puncture, can be extremely taxing and invasive for patients. Here, we wanted to get a better sense of when these interventions are necessary versus when we could do without them.”

Each of the three methods, MRI, LP, and EEG, have been used to manage the care of patients of CAR T-cell therapy who experience immune effector cell-associated neurotoxicity syndrome (ICANS). Patients with this condition can experience a range of neurological symptoms including confusion, tremors, and seizures. In its most serious form, ICANS can also lead to serious brain swelling and coma.

Current treatment guideline for ICANS recommend the use of any of the three diagnostic modalities for ICANS based on the severity of the symptoms to help determine the best treatments. But these methods can be either expensive, or invasive and require extensive hospital resource utilization. Further, the diagnostic techniques used, more usually rule out conditions other than ICANS, and the treatment regimen is rarely altered based on the findings.

For this study, the team collected data from 190 patients who had been treated with CAR T cells between August 2018 and January 2023 at the University Hospital Centre of Rennes. The average age of patients was 64 (with ages ranging from 15 to 81) and 62% of study subjects were male. Of the total, 73% were being treated for refractory/relapsed diffuse large B cell lymphoma (DLBCL), and 48% of all participant experienced some form of ICANS.

Prior to receiving CAR T-cell therapy the participants had a baseline assessment from an MRI scan. Of the patients who experience ICANS, their treatment and diagnostic protocol were dependent on their unique symptoms and physician recommendations using existing medical guidelines. Eighty percent of the patients with ICANS underwent at least one of the three interventions, and roughly one-third (34%) underwent all three.

Patients who received an MRI scan (78%) showed that eight in ten returned normal results and only four percent of those with abnormal findings had their treatment plan changed as a result. Nearly half of the patients (47%) received lumbar puncture and while no active infections were identified, seven percent of patients had their treatment changed based on suspected infections.

By comparison, 45% of patients who received an EEG showed brain dysfunction and in some of these cases signs of seizures, even in those with no prior symptoms. In total, EEG testing resulted in a change of treatment plans in 16% of cases based on abnormal results.

Not surprisingly, abnormal test results were more common among people with more severe ICANS, though MRI often returned normal results while LP and EEG showed abnormalities.

Manson noted that these study results will require further validation due to the limited size of this initial work. But the results do suggest that MRI and LP might not always be necessary as part of the management of patients with ICANS, while an EEG assessment more often led to adjusting medications. His hope is that with further research current medical guidelines could be amended to better indicate in what circumstances each of the interventions is recommended.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” said Manson. “We did this research to generate clinical evidence to inform guidelines that support physicians in making clinical decisions when treating patients with these complex, and sometimes severe conditions.”

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