Study Results Show Certain Interventions Unnecessary in Managing Complications From CAR T-Cell Therapy


Findings show that magnetic resonance imaging and lumbar puncture are not always needed when managing complications of CAR T-cell therapies, but may be beneficial in certain cases.

Study results published in Blood Advances demonstrate that magnetic resonance imaging (MRI) and lumbar puncture (LP) are not always necessary when diagnosing and managing serious neurological complications associated with chimeric antigen receptor (CAR) T-cell therapy. In addition, the study had also indicated that the electroencephalogram (EEG) is effective in managing neurotoxicities.1

MRI machine -- Image credit: phonlamaiphoto |

Image credit: phonlamaiphoto |

According to national and international diagnostic guidelines, it is recommended that health care providers perform an MRI, and a LP either with or without an EEG—depending on the severity of the condition—prior to initiation of immune effector cell-associated neurotoxicity syndrome (ICANS) treatment. Although the underlying conditions of ICANS have yet to be fully understood, patients can experience a variety of neurological symptoms including seizures, confusion, tremors, as well as—in rarer cases—brain swelling and comas.1

Although the 3 interventions—MRI, LP, and EEG—can be both expensive and invasive for patients with ICANS, they are helpful in ruling out other conditions and treatments that are rarely modified by the test results. The study authors wanted to evaluate the necessity of the diagnostic testing methods that are used to manage care for recipients of CAR T-cell therapy who are experiencing ICANS.1

“When treating patients for CAR T-cell associated toxicities, we typically follow pretty rigid guidelines based on phase 1 and 2 studies, and there is little to no clinical evidence to validate these,” said senior study author Guillaume Manson, hematologist, University Hospital of Rennes in Rennes, France, in a press release. “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.”1

A total of 190 patients aged 15 to 81 years (average of 64 years) who were treated with CAR T-cell therapy were enrolled in the study. The majority of patients (73%) were treated for refractory or relapsed diffused large B cell lymphoma (DLBCL), but all participants met with a neurologist and underwent an MRI scan as a baseline assessment prior to administration of CAR T-cell infusions.1

Approximately 48% of patients developed ICANS, and among those who developed it, their treatment protocol was dependent on their case and physician’s recommendation to adhere to current guidelines. Most patients with ICANS (80%) had underwent at least 1 intervention, with approximately 34% undergoing all 3 interventions. In addition, 74% of patients underwent MRI scans, of which 80% had scans that indicated normal results. Further, only 4% of these patients had abnormal findings, which required a change in their treatment plans. About 47% of patients underwent LP and although no cases had identified active infections, 7% of patients had to undergo changes in treatment because of suspected infections. Further, of the 56% of patients who received EEGs, 18% showed normal results on their scans; however, in 45% of patients, brain dysfunction was detected as well as signs of seizures without prior symptoms in some cases. This finding resulted in 16% of treatment plans being altered.1,2

The investigators observed that abnormal results were more common in patients who had more severe ICANS, and that MRI results were more likely to be normal compared to LP and EEG, which showed more abnormalities and consistent with severe ICANS. Further, MRI scans rarely led to changes in treatment decisions, however, LP and EEG sometimes led to unnecessary treatments for suspected infections and adjustments to antiepileptic medications, respectively.1

The study authors note that there are limitations due to a small sample size enrolled in the trial, requiring further research and validation to confirm the findings. Although the findings show that LP and MRI is not always necessary for patients with ICANs because they did not frequently influence treatment, EEG more often led to adjustments made in medications, indicating that this method may be necessary in diagnostic interventions. The investigators also emphasized that the findings are an indicator that changes to existing guidelines for ICANS management are necessary.1,2

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” said Manson in the press release. “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.”1


1. American Society of Hematology. MRI and Lumbar Puncture Not Necessarily Required to Manage CAR T-Cell Therapy Complications. News release. March 19, 2024. Accessed March 20, 2024.
2. Mauget, M, Lemercier, S, Quelven, Q, et al. Impact of diagnostic investigations in the management of CAR T-cell-associated neurotoxicity. Blood Adv 2024; doi:10.1182/bloodadvances.2023011669
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