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“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.
The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.
ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.
However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.
While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.
To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.
Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.
The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.
While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.
Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.
While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.
“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.
The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
EEG Findings
Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.
Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.
Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.
Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).
In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.
Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.
A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.
With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.
Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.
“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.
“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.
“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.
Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.
“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.
“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,” he added.
Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.
“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.
The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.
ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.
However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.
While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.
To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.
Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.
The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.
While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.
Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.
While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.
“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.
The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
EEG Findings
Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.
Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.
Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.
Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).
In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.
Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.
A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.
With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.
Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.
“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.
“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.
“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.
Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.
“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.
“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,” he added.
Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.
“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.
The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.
ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.
However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.
While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.
To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.
Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.
The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.
While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.
Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.
While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.
“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.
The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
EEG Findings
Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.
Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.
Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.
Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).
In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.
Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.
A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.
With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.
Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.
“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.
“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.
“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.
Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.
“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.
“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,” he added.
Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.
FROM BLOOD ADVANCES