Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a potential complication following Chimeric Antigen Receptor (CAR) T-cell infusion. Biomarkers to aid in early diagnosis and severity assessment are lacking. We aim to describe and compare serum neurofilament light chain (sNfL) dynami...

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Autores: Vilaseca, Andreu|||0000-0001-8147-8505, Ariño, Helena|||0000-0003-4036-1671, Iacoboni, Gloria|||0000-0003-0805-9288, Feijoo, Samantha, Zabalza, Ana|||0000-0003-3860-5251, Fissolo, Nicolás|||0000-0002-7701-9346, Arévalo, María Jesús|||0000-0003-0626-5555, Carpio Segura, Cecilia del Carmen|||0000-0001-9346-0134, Tintoré, Mar|||0000-0001-9999-5359, Comabella López, Manuel|||0000-0002-2373-6657, Montalban, Xavier|||0000-0002-0098-9918, Barba, Pere|||0000-0001-7076-7969, Vidal-Jordana, Angela|||0000-0002-7270-5507
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:dnet:uabarcelona_::5f7834e40d6235f883c909bd6f45cc5d
Acceso en línea:https://ddd.uab.cat/record/328388
https://dx.doi.org/urn:doi:10.1111/ene.70305
Access Level:acceso abierto
Palabra clave:Autoimmune neurology
Biomarker
CAR-T cells
ICANS
Immunotherapy
Lymphoma
Neuroaxonal damage
Oncology
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spelling Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell TherapyVilaseca, Andreu|||0000-0001-8147-8505Ariño, Helena|||0000-0003-4036-1671Iacoboni, Gloria|||0000-0003-0805-9288Feijoo, SamanthaZabalza, Ana|||0000-0003-3860-5251Fissolo, Nicolás|||0000-0002-7701-9346Arévalo, María Jesús|||0000-0003-0626-5555Carpio Segura, Cecilia del Carmen|||0000-0001-9346-0134Tintoré, Mar|||0000-0001-9999-5359Comabella López, Manuel|||0000-0002-2373-6657Montalban, Xavier|||0000-0002-0098-9918Barba, Pere|||0000-0001-7076-7969Vidal-Jordana, Angela|||0000-0002-7270-5507Autoimmune neurologyBiomarkerCAR-T cellsICANSImmunotherapyLymphomaNeuroaxonal damageOncologyImmune effector cell-associated neurotoxicity syndrome (ICANS) is a potential complication following Chimeric Antigen Receptor (CAR) T-cell infusion. Biomarkers to aid in early diagnosis and severity assessment are lacking. We aim to describe and compare serum neurofilament light chain (sNfL) dynamics in non-Hodgkin lymphoma (NHL) patients undergoing anti-CD19 CAR T-cell therapy, based on ICANS presence and severity. This is a case-control study nested within a cohort of NHL patients treated with anti-CD19 CAR T-cells at a tertiary care center. From this cohort, we selected those who developed ICANS and had available blood samples. These patients were compared to matched NHL patients without ICANS from the same cohort. sNfL concentrations were measured immediately pre-infusion and on days 7 and 14 post-infusion, with z -scores calculated against a normative database. Mixed linear and ROC analysis assessed sNfL dynamics by ICANS presence and severity. Of 159 patients treated, 54 (34%) developed ICANS. We included 32 patients with ICANS and 22 matched controls. Baseline sNfL concentrations were similarly elevated in both ICANS and non-ICANS patients. However, on day 7, patients with moderate-severe ICANS (grade ≥ 2) had higher sNfL levels (median z -score 2.33) than those with mild or no ICANS (median z -score 1.72; p = 0.022). The optimal cutoff to discriminate moderate-severe ICANS from other patients based on sNfL was a z -score of 2.14 on day 7 (p = 0.004). Moderate-severe ICANS is associated with elevated sNfL levels by day 7 post-infusion, indicating early neuroaxonal damage and underscoring sNfL as a valuable biomarker for assessing ICANS severity. 22025-01-0120252025-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/328388https://dx.doi.org/urn:doi:10.1111/ene.70305reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:dnet:uabarcelona_::5f7834e40d6235f883c909bd6f45cc5d2026-06-06T12:50:31Z
dc.title.none.fl_str_mv Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
title Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
spellingShingle Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
Vilaseca, Andreu|||0000-0001-8147-8505
Autoimmune neurology
Biomarker
CAR-T cells
ICANS
Immunotherapy
Lymphoma
Neuroaxonal damage
Oncology
title_short Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
title_full Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
title_fullStr Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
title_full_unstemmed Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
title_sort Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy
dc.creator.none.fl_str_mv Vilaseca, Andreu|||0000-0001-8147-8505
Ariño, Helena|||0000-0003-4036-1671
Iacoboni, Gloria|||0000-0003-0805-9288
Feijoo, Samantha
Zabalza, Ana|||0000-0003-3860-5251
Fissolo, Nicolás|||0000-0002-7701-9346
Arévalo, María Jesús|||0000-0003-0626-5555
Carpio Segura, Cecilia del Carmen|||0000-0001-9346-0134
Tintoré, Mar|||0000-0001-9999-5359
Comabella López, Manuel|||0000-0002-2373-6657
Montalban, Xavier|||0000-0002-0098-9918
Barba, Pere|||0000-0001-7076-7969
Vidal-Jordana, Angela|||0000-0002-7270-5507
author Vilaseca, Andreu|||0000-0001-8147-8505
author_facet Vilaseca, Andreu|||0000-0001-8147-8505
Ariño, Helena|||0000-0003-4036-1671
Iacoboni, Gloria|||0000-0003-0805-9288
Feijoo, Samantha
Zabalza, Ana|||0000-0003-3860-5251
Fissolo, Nicolás|||0000-0002-7701-9346
Arévalo, María Jesús|||0000-0003-0626-5555
Carpio Segura, Cecilia del Carmen|||0000-0001-9346-0134
Tintoré, Mar|||0000-0001-9999-5359
Comabella López, Manuel|||0000-0002-2373-6657
Montalban, Xavier|||0000-0002-0098-9918
Barba, Pere|||0000-0001-7076-7969
Vidal-Jordana, Angela|||0000-0002-7270-5507
author_role author
author2 Ariño, Helena|||0000-0003-4036-1671
Iacoboni, Gloria|||0000-0003-0805-9288
Feijoo, Samantha
Zabalza, Ana|||0000-0003-3860-5251
Fissolo, Nicolás|||0000-0002-7701-9346
Arévalo, María Jesús|||0000-0003-0626-5555
Carpio Segura, Cecilia del Carmen|||0000-0001-9346-0134
Tintoré, Mar|||0000-0001-9999-5359
Comabella López, Manuel|||0000-0002-2373-6657
Montalban, Xavier|||0000-0002-0098-9918
Barba, Pere|||0000-0001-7076-7969
Vidal-Jordana, Angela|||0000-0002-7270-5507
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Autoimmune neurology
Biomarker
CAR-T cells
ICANS
Immunotherapy
Lymphoma
Neuroaxonal damage
Oncology
topic Autoimmune neurology
Biomarker
CAR-T cells
ICANS
Immunotherapy
Lymphoma
Neuroaxonal damage
Oncology
description Immune effector cell-associated neurotoxicity syndrome (ICANS) is a potential complication following Chimeric Antigen Receptor (CAR) T-cell infusion. Biomarkers to aid in early diagnosis and severity assessment are lacking. We aim to describe and compare serum neurofilament light chain (sNfL) dynamics in non-Hodgkin lymphoma (NHL) patients undergoing anti-CD19 CAR T-cell therapy, based on ICANS presence and severity. This is a case-control study nested within a cohort of NHL patients treated with anti-CD19 CAR T-cells at a tertiary care center. From this cohort, we selected those who developed ICANS and had available blood samples. These patients were compared to matched NHL patients without ICANS from the same cohort. sNfL concentrations were measured immediately pre-infusion and on days 7 and 14 post-infusion, with z -scores calculated against a normative database. Mixed linear and ROC analysis assessed sNfL dynamics by ICANS presence and severity. Of 159 patients treated, 54 (34%) developed ICANS. We included 32 patients with ICANS and 22 matched controls. Baseline sNfL concentrations were similarly elevated in both ICANS and non-ICANS patients. However, on day 7, patients with moderate-severe ICANS (grade ≥ 2) had higher sNfL levels (median z -score 2.33) than those with mild or no ICANS (median z -score 1.72; p = 0.022). The optimal cutoff to discriminate moderate-severe ICANS from other patients based on sNfL was a z -score of 2.14 on day 7 (p = 0.004). Moderate-severe ICANS is associated with elevated sNfL levels by day 7 post-infusion, indicating early neuroaxonal damage and underscoring sNfL as a valuable biomarker for assessing ICANS severity.
publishDate 2025
dc.date.none.fl_str_mv 2
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/328388
https://dx.doi.org/urn:doi:10.1111/ene.70305
url https://ddd.uab.cat/record/328388
https://dx.doi.org/urn:doi:10.1111/ene.70305
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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