Value of MRI, lumbar puncture questioned for immune cell-associated neurotoxicity syndrome
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Key takeaways:
- Clinicians rarely made therapeutic modifications based on MRI and lumbar puncture results.
- EEGs may be underutilized as a diagnostic tool for patients with ICANS.
MRIs and lumbar punctures may not provide enough therapeutic value to be standard-of-care diagnostic tests in patients suffering neurologic symptoms following chimeric antigen receptor T-cell therapy.
The findings of a retrospective study, published in Blood Advances, showed results of those diagnostic investigations rarely led to treatment modifications in individuals suffering from immune cell-associated neurotoxicity syndrome (ICANS), whereas electroencephalograms (EEGs) produced substantially more alterations.
“Our study shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and [lumbar punctures] appear to have a limited therapeutic impact,” researchers wrote. “Our results emphasize the role of EEG in the current guidelines, but [question] the need for systematic MRI and [lumbar puncture], which might be left to the discretion of the treating physician.”
John Baird, MD, assistant professor at City of Hope, reviewed the study and agreed on the value of EEGs, adding they tend to be “underutilized” in practice, but he questioned the conclusions regarding MRIs and lumbar punctures (LPs).
“We’re trying to make sure with some of this testing that we’re not missing some other reason besides just blaming it on the CAR T cells for why this patient became confused,” Baird told Healio. “Whether it’s an electrolyte imbalance, a fluid overload causing fluid in the lungs or trouble breathing, or an infection of some variety, I think that getting a negative test result is not necessarily completely useless because it does take a possibility off the table.”
Background and methods
CAR T-cell therapies have emerged for multiple hematologic malignancies over the last several years, and although they have proven effective, ICANS is a common treatment-related toxicity.
Global guidelines have recommended MRIs, LPs and EEGs as diagnostic tools to to confirm or rule out various diagnoses, according to background information provided by researchers.
“There is little to no clinical evidence to validate these,” Guillaume Manson, MD, a hematologist at University Hospital of Rennes, France, said in a press release. “Some of these tests, like a lumbar puncture, can be extremely taxing and invasive for patients,” he added. “Here, we wanted to get a better sense of when these interventions are necessary.”
Researchers evaluated 190 patients (median age, 64 years; 62% men; 48% had ICANS) treated with CAR-T at University Hospital of Rennes between August 2018 and January 2023.
They evaluated therapeutic modifications as the study’s primary endpoint.
For MRI, that meant changes to central nervous system-directed therapies, or alternations in management if the patient had nervous system involvement.
For LPs, modifications meant use of anti-infectious agents. For EEGs, they looked for changes in antiepileptics.
Results
Of patients who had ICANS, 80% underwent at least one of the diagnostic tests, and 34% had all three.
Clinicians conducted MRIs most often (78%) followed by EEGs (56%) and LP (47%).
MRIs produced normal results 80% of the time, including a range of 81% to 91% in grade 1 to grade 3 ICANS. Patients with grade 4 ICANS had mostly abnormal MRIs (58%).
The most common abnormal MRIs included aspecific hypersignal and stroke.
Only 4% of MRIs resulted in therapeutic modifications.
LPs did not detect any infections, although 7% of patients did have preemptive anti-infectious agents.
Abnormal EEGs occurred in 82% of individuals, including encephalopathy (45%) and seizure or status epilepticus (12%).
EEG results produced therapeutic modifications in 16% of patients, including in 24% of those with grade 3 or higher ICANS.
“EEG can have more value than has previously been attributed to it for managing ICANS,” Baird said, citing this as his primary takeaway from the study. “Unlike MRI and lumbar puncture, which are things that the primary team on the inpatient side, have a little bit more control over doing in a quicker fashion, with EEG we’re often at the mercy of the consulting teams, the neurologists and the technicians and the folks who are actually setting up and doing the EEG monitoring.”
Value of negative, next steps
Researchers did not say MRIs and LPs should not be performed.
“Our results highlight the need for novel ICANS management guidelines, which will limit the use of investigations to situations with a significant therapeutic impact and with an optimal risk-benefit ratio,” they wrote.
Baird believed the researchers may have discounted their utility too much.
“I want to see a little bit more under the hood,” he said. “For a lot of us who manage these patients, one of the core questions you’re always faced with ... is it true ICANS or is it some mimic that it is something else, like an infection?”
That answer can determine how much immune suppression a patient receives, thus doing an LP can have benefit despite no therapeutic modifications.
“By this study’s kind of accounting, that would be counted as this was useless. We didn’t actually find a new diagnosis that we’re going to treat,” he said. “We can, anecdotally, think back in the not-too-distant past and remember when we caught a viral infection, or when we caught an area of focal edema that we treated, and it seemed like the thing that really helped the patient get over the most severe parts of this experience.”
Baird did say the numbers showed clinicians could be more “discretionary in our ordering of head imaging and doing invasive procedures,” but highlighted the need for more research to find diagnostic tools that can produce answers.
“It’s kind of the million-dollar question from the research side,” Baird said. “There’s not necessarily a diagnostic gold standard to send off where you could say with a lot of confidence this has to be ICANS and can’t be anything else.”
References:
- Mauget M, et al. Blood Adv. 2024;doi:10.1182/bloodadvances.2023011669.
- MRI and lumbar puncture not necessarily required to manage CAR T-cell therapy complications (press release). Available at: https://www.hematology.org/newsroom/press-releases/2024/mri-and-lumbar-puncture-not-necessarily-required-to-manage-car-t-cell-therapy-complications. Published March 19, 2024. Accessed April 12, 2024.
For more information:
John Baird, MD, can be reached at jbaird@coh.org.
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Mauget M, et al. Blood Adv. 2024;doi:10.1182/bloodadvances.2023011669.
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