CAR T-Cell Therapy Complications: Comparison of Three Testing Modalities

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Magnetic resonance imaging (MRI) and lumbar puncture may not always be necessary for diagnosing and managing a serious neurologic complication associated with chimeric antigen receptor (CAR) T-cell therapy, according to a new study published by Mauget et al in Blood Advances. Findings further validated the use of the electroencephalogram (EEG)—a noninvasive test measuring electrical activity in the brain—in managing this neurotoxicity.

“When treating patients for CAR T-cell–associated toxicities, we typically follow pretty rigid guidelines based on phase I and II studies, and there is little to no clinical evidence to validate these,” explained senior study author Guillaume Manson, MD, 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 vs when we could do without them.”

Study Details

The study authors sought to evaluate the necessity of three diagnostic tests used to manage care for recipients of CAR T-cell therapy experiencing immune effector cell–associated neurotoxicity syndrome (ICANS). While the underlying mechanisms of ICANS are not entirely understood, patients with the syndrome may experience a range of neurologic symptoms, including confusion, tremors, seizures, and, in rare cases, serious brain swelling and comas.

National and international diagnostic guidelines recommend that health-care providers perform an MRI, a lumbar puncture, and/or an EEG, based on a complication’s severity, before beginning ICANS treatment. These interventions are expensive, can be invasive, and require extensive hospital resources. Further, these interventions are typically used to rule out other conditions, and treatments are seldom modified by the results of these tests.

The study authors collected data from 190 patients treated with CAR T-cell therapy at the University Hospital Centre of Rennes from August 2018 to January  2023. Among all the patients in the study, about 62% were male, and the average age was 64 years old, with ages ranging from 15 to 81 years. Most of the patients—about 73%—were being treated for refractory or relapsed diffuse large B-cell lymphoma. During treatment, roughly 48% of patients developed ICANS.

All study participants met with a neurologist and underwent an MRI as a baseline assessment before receiving CAR T-cell infusions. Among those who experienced ICANS, the treatment protocol depended on their unique case and physician recommendation, abiding by the existing guidelines. Most patients with ICANS (80%) underwent at least one intervention, and a third (34%) underwent all three (MRI, lumbar puncture, and EEG).

Study Findings

Researchers assessed how the different interventions affected patient treatment, such as how medications (for example, antibiotics and antiseizure therapy) were prescribed based on abnormal findings, and how these treatment courses changed patient outcomes. Among the 78% of patients who underwent MRI, 80% of scans showed normal results. Only 4% of those with abnormal findings had a change in treatment plans. Approximately 47% of patients underwent lumbar punctures, and no cases identified active infections, but 7% of patients had a treatment change based on suspected infections.

Among the 56% of patients who received EEGs, only 18% of these scans showed normal results. In 45% of patients, EEGs detected brain dysfunction, and in some cases, signs of seizures, even in those with no prior symptoms. As a result, 16% of treatment plans were altered based on abnormal EEG findings.

Results ultimately revealed that abnormal results were more common in patients with more severe ICANS. MRI results were often normal, and while lumbar puncture and EEG often showed abnormalities, it was more frequent with more severe cases of ICANS. When it came to treatment decisions, MRI rarely led to changes, lumbar puncture sometimes led to unnecessary treatments for suspected infections, and EEG often resulted in adjustments to antiepileptic medications.

This study is limited by its relatively small sample size and requires validation by further clinical studies. These findings suggest that lumbar puncture and MRI might not always be necessary for all patients with ICANS, as they often did not influence treatment. However, EEG often led to adjustments in medications, suggesting it remains a necessary diagnostic intervention.

Ultimately, Dr. Manson conveyed that these results represent a call to action to update existing guidelines for managing ICANS based on clinical evidence. He emphasized that these results do not imply that practitioners should never perform MRI or lumbar puncture—only that they may not be needed in all cases. If further evidence confirms that MRI and lumbar puncture are not necessary in all instances of ICANS, revised guidelines could potentially save patients time and money, as well as spare them from unnecessary medical procedures.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” said Dr. 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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