Brain FDG-PET findings in chimeric antigen receptor T-cell therapy neurotoxicity for diffuse large B-cell lymphoma
© 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging..
BACKGROUND AND PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy is potentially associated with treatment-related toxicities mainly consisting of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B-cell lymphoma patients treated with CAR-T.
METHODS: Twenty-one refractory DLCBLs underwent whole-body and brain [18 F]-fluorodeoxyglucose (FDG) PET before and 30 days after treatment with CAR-T. Five patients did not develop inflammatory-related side effects, 11 patients developed CRS, while in 5 patients CRS evolved in ICANS. Baseline and post-CAR-T brain FDG-PET were compared with a local controls dataset to identify hypometabolic patterns both at single-patient and group levels (p < .05 after correction for family-wise error [FWE). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed on baseline FDG-PET and compared between patients' subgroups (t-test).
RESULTS: ICANS showed an extended and bilateral hypometabolic pattern mainly involving the orbitofrontal cortex, frontal dorsolateral cortex, and anterior cingulate (p < .003 FWE-corrected). CRS without ICANS showed significant hypometabolism in less extended clusters mainly involving bilateral medial and lateral temporal lobes, posterior parietal lobes, anterior cingulate, and cerebellum (p < .002 FWE-corrected). When compared, ICANS showed a more prominent hypometabolism in the orbitofrontal and frontal dorsolateral cortex in both hemispheres than CRS (p < .002 FWE-corrected). Mean baseline MTV and TLG were significantly higher in ICANS than CRS (p < .02).
CONCLUSIONS: Patients with ICANS are characterized by a frontolateral hypometabolic signature coherently with the hypothesis of ICANS as a predominant frontal syndrome and with the more prominent susceptibility of frontal lobes to cytokine-induced inflammation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Journal of neuroimaging : official journal of the American Society of Neuroimaging - 33(2023), 5 vom: 08. Sept., Seite 825-836 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Morbelli, Silvia [VerfasserIn] |
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| Links: |
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| Themen: |
0Z5B2CJX4D |
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| Anmerkungen: |
Date Completed 02.11.2023 Date Revised 11.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/jon.13135 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM35793251X |
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| 100 | 1 | |a Morbelli, Silvia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Brain FDG-PET findings in chimeric antigen receptor T-cell therapy neurotoxicity for diffuse large B-cell lymphoma |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 02.11.2023 | ||
| 500 | |a Date Revised 11.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging. | ||
| 520 | |a BACKGROUND AND PURPOSE: Chimeric antigen receptor (CAR) T-cell therapy is potentially associated with treatment-related toxicities mainly consisting of cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS). We evaluated brain metabolic correlates of CRS with and without ICANS in diffuse large B-cell lymphoma patients treated with CAR-T | ||
| 520 | |a METHODS: Twenty-one refractory DLCBLs underwent whole-body and brain [18 F]-fluorodeoxyglucose (FDG) PET before and 30 days after treatment with CAR-T. Five patients did not develop inflammatory-related side effects, 11 patients developed CRS, while in 5 patients CRS evolved in ICANS. Baseline and post-CAR-T brain FDG-PET were compared with a local controls dataset to identify hypometabolic patterns both at single-patient and group levels (p < .05 after correction for family-wise error [FWE). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were computed on baseline FDG-PET and compared between patients' subgroups (t-test) | ||
| 520 | |a RESULTS: ICANS showed an extended and bilateral hypometabolic pattern mainly involving the orbitofrontal cortex, frontal dorsolateral cortex, and anterior cingulate (p < .003 FWE-corrected). CRS without ICANS showed significant hypometabolism in less extended clusters mainly involving bilateral medial and lateral temporal lobes, posterior parietal lobes, anterior cingulate, and cerebellum (p < .002 FWE-corrected). When compared, ICANS showed a more prominent hypometabolism in the orbitofrontal and frontal dorsolateral cortex in both hemispheres than CRS (p < .002 FWE-corrected). Mean baseline MTV and TLG were significantly higher in ICANS than CRS (p < .02) | ||
| 520 | |a CONCLUSIONS: Patients with ICANS are characterized by a frontolateral hypometabolic signature coherently with the hypothesis of ICANS as a predominant frontal syndrome and with the more prominent susceptibility of frontal lobes to cytokine-induced inflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CAR-T | |
| 650 | 4 | |a brain PET | |
| 650 | 4 | |a lymphoma | |
| 650 | 4 | |a neuroinflammation | |
| 650 | 7 | |a Receptors, Chimeric Antigen |2 NLM | |
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| 650 | 7 | |a Fluorodeoxyglucose F18 |2 NLM | |
| 650 | 7 | |a 0Z5B2CJX4D |2 NLM | |
| 700 | 1 | |a Gambella, Massimiliano |e verfasserin |4 aut | |
| 700 | 1 | |a Raiola, Anna Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Ghiggi, Chiara |e verfasserin |4 aut | |
| 700 | 1 | |a Bauckneht, Matteo |e verfasserin |4 aut | |
| 700 | 1 | |a Raimondo, Tania Di |e verfasserin |4 aut | |
| 700 | 1 | |a Lapucci, Caterina |e verfasserin |4 aut | |
| 700 | 1 | |a Sambuceti, Gianmario |e verfasserin |4 aut | |
| 700 | 1 | |a Inglese, Matilde |e verfasserin |4 aut | |
| 700 | 1 | |a Angelucci, Emanuele |e verfasserin |4 aut | |
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