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Chimeric Antigen Receptor T-Cell Therapy: Are Neuroradiologists Prepared?

Chimeric Antigen Receptor T-Cell Therapy: Are Neuroradiologists Prepared? LETTERS Chimeric Antigen Receptor T-Cell Therapy: Are Neuroradiologists Prepared? read with interest the Practice Vignette by Valand et al with neurotoxicity compared with pretreatment. In addition, Gust regard to neurotoxicity of chimeric antigen receptor T-cell et al demonstrated increased CSF levels of S100 calcium bind- (CAR T) therapy for hematologic cancers. The authors con- ing protein B and glial fibrillary acidic protein in patients with cluded that brain MR imaging is unremarkable in mild forms of neurotoxicity, indicating astrocyte injury, which would explain neurotoxicity and only demonstrates nonspecific findings in the the presence of cerebral edema, given the key role of glial cells context of severe neurotoxicity, which can resemble chronic mi- in osmotic regulation in the brain. crovascular ischemia and migraine. While I agree that the imag- In conclusion, neuroradiologists should have a high level of ing findings are not pathognomonic, 2 case series in patients with suspicion for CAR T therapy neurotoxicity in patients with severe CD19-directed CAR T–induced neurotoxicity showed bilateral thalamic and brain stem involvement. Designing pro- similar imaging findings of bilateral thalamic and brain stem spective studies with advanced MR imaging sequences focus- involvement with extension to the basal gangRlia and extreme ing on the detection of early brain edema would be crucial to capsule, resembling central-variant posterior reversible encephal- better understand this entity and discover early imaging find- opathy syndrome or acute necrotizing encephalopathy in a subset ings of CAR T therapy neurotoxicity. 2,3 of patients. Another reported imaging finding was transient lesions of the splenium of the corpus callosum characterized by restricted diffusion and T2 prolongation with resolution on REFERENCES subsequent imaging. In addition, a recent study indicated re- 1. Valand HA, Huda F, Tu RK. Chimeric antigen receptor t-cell stricted diffusion in the bilateral occipital cortex, which demon- therapy: what the neuroradiologist needs to know. AJNR Am J strated hypometabolism on subsequent FDG-PET imaging. Neuroradiol 2019;40:766–68 CrossRef Medline 2. Santomasso BD, Park JH, Salloum D, et al. Clinical and biological Considering that all the available studies only reported findings correlates of neurotoxicity associated with CAR t-cell therapy in on conventional MR imaging, it should not be surprising that the patients with b-cell acute lymphoblastic leukemia. Cancer Discov authors detected abnormalities only in a subset of patients with 2018;8:958–71 CrossRef Medline severe neurotoxicity. 3. Gust J, Finney OC, Li D, et al. Glial injury in neurotoxicity after pedi- CAR T therapy neurotoxicity represents a continuum rang- atric cd19-directed chimeric antigen receptor t cell therapy. Ann Neurol 2019;86:42–54 CrossRef Medline ing from different degrees of neurotoxicity to severe brain edema in lethal cases, which is corroborated by postmortem 2,3 2 studies. Santomasso et al analyzed excitatory agonists such S.A. Nabavizadeh Department of Radiology as glutamate (Glut) and quinolinic acid (QA) in the CSF of 13 Hospital of University of Pennsylvania patients receiving CD19-directed CAR T treatment and demon- Perelman School of Medicine of the University of Pennsylvania strated a significant increase in Glut and QA CSF levels during Philadelphia, Pennsylvania http://dx.doi.org/10.3174/ajnr.A6186 E52 Letters Oct 2019 www.ajnr.org http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Neuroradiology American Journal of Neuroradiology

Chimeric Antigen Receptor T-Cell Therapy: Are Neuroradiologists Prepared?

American Journal of Neuroradiology , Volume 40 (10) – Oct 1, 2019

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Publisher
American Journal of Neuroradiology
ISSN
0195-6108
eISSN
1936-959X
DOI
10.3174/ajnr.A6186
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Abstract

LETTERS Chimeric Antigen Receptor T-Cell Therapy: Are Neuroradiologists Prepared? read with interest the Practice Vignette by Valand et al with neurotoxicity compared with pretreatment. In addition, Gust regard to neurotoxicity of chimeric antigen receptor T-cell et al demonstrated increased CSF levels of S100 calcium bind- (CAR T) therapy for hematologic cancers. The authors con- ing protein B and glial fibrillary acidic protein in patients with cluded that brain MR imaging is unremarkable in mild forms of neurotoxicity, indicating astrocyte injury, which would explain neurotoxicity and only demonstrates nonspecific findings in the the presence of cerebral edema, given the key role of glial cells context of severe neurotoxicity, which can resemble chronic mi- in osmotic regulation in the brain. crovascular ischemia and migraine. While I agree that the imag- In conclusion, neuroradiologists should have a high level of ing findings are not pathognomonic, 2 case series in patients with suspicion for CAR T therapy neurotoxicity in patients with severe CD19-directed CAR T–induced neurotoxicity showed bilateral thalamic and brain stem involvement. Designing pro- similar imaging findings of bilateral thalamic and brain stem spective studies with advanced MR imaging sequences focus- involvement with extension to the basal gangRlia and extreme ing on the detection of early brain edema would be crucial to capsule, resembling central-variant posterior reversible encephal- better understand this entity and discover early imaging find- opathy syndrome or acute necrotizing encephalopathy in a subset ings of CAR T therapy neurotoxicity. 2,3 of patients. Another reported imaging finding was transient lesions of the splenium of the corpus callosum characterized by restricted diffusion and T2 prolongation with resolution on REFERENCES subsequent imaging. In addition, a recent study indicated re- 1. Valand HA, Huda F, Tu RK. Chimeric antigen receptor t-cell stricted diffusion in the bilateral occipital cortex, which demon- therapy: what the neuroradiologist needs to know. AJNR Am J strated hypometabolism on subsequent FDG-PET imaging. Neuroradiol 2019;40:766–68 CrossRef Medline 2. Santomasso BD, Park JH, Salloum D, et al. Clinical and biological Considering that all the available studies only reported findings correlates of neurotoxicity associated with CAR t-cell therapy in on conventional MR imaging, it should not be surprising that the patients with b-cell acute lymphoblastic leukemia. Cancer Discov authors detected abnormalities only in a subset of patients with 2018;8:958–71 CrossRef Medline severe neurotoxicity. 3. Gust J, Finney OC, Li D, et al. Glial injury in neurotoxicity after pedi- CAR T therapy neurotoxicity represents a continuum rang- atric cd19-directed chimeric antigen receptor t cell therapy. Ann Neurol 2019;86:42–54 CrossRef Medline ing from different degrees of neurotoxicity to severe brain edema in lethal cases, which is corroborated by postmortem 2,3 2 studies. Santomasso et al analyzed excitatory agonists such S.A. Nabavizadeh Department of Radiology as glutamate (Glut) and quinolinic acid (QA) in the CSF of 13 Hospital of University of Pennsylvania patients receiving CD19-directed CAR T treatment and demon- Perelman School of Medicine of the University of Pennsylvania strated a significant increase in Glut and QA CSF levels during Philadelphia, Pennsylvania http://dx.doi.org/10.3174/ajnr.A6186 E52 Letters Oct 2019 www.ajnr.org

Journal

American Journal of NeuroradiologyAmerican Journal of Neuroradiology

Published: Oct 1, 2019

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