ArticleJournal for immunotherapy of cancer2024
Neurofilament light chain levels as an early predictive biomarker of neurotoxicity after CAR T-cell therapy.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The gut microbiota-brain-CAR T cell axis: a systematic review of gut microbiome modulation and its impact on neurological complications and treatment responses in CAR T cell therapy.Frontiers in immunology · 2025Pooled it
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- Predictive Models for Toxicities after CAR T-cell Therapy: Challenges and Opportunities.Blood cancer discovery · 2026Review
- Neuronal injury biomarkers GFAP and neurofilament light chains (NfL) are associated with neurotoxicity and endothelial dysfunction in adult patients treated with antiCD19 CART cells.Clinical and experimental medicine · 2026Article
- Case Report: CAR-T therapy for relapsed diffuse large B-cell lymphoma in a patient with pre-existing Parkinson's disease-unfolding clinical challenges.Frontiers in oncology · 2026Article
- Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy.European journal of neurology · 2025Article
- Baseline Cognitive and Neurological Status Does Not Modify the Occurrence of ICANS in CAR T-Cell Therapy for Aggressive B-Cell Lymphoma.European journal of neurology · 2025Article
- The Struggle Between Chimeric Antigen Receptor T-Cell Therapy and Neurological Complications in Acute Lymphoblastic Leukemia Treatment.Current issues in molecular biology · 2025Review
- Biology-driven therapies of CAR T immune effector cell-associated neurotoxicity syndrome.Immunotherapy · 2025Review
- Immune Effector Cell-Associated Neurotoxicity Syndrome After CAR T-Cell Therapy and Other Psychiatric Manifestations: A Review and Case Series.Journal of clinical medicine · 2025Review
- In-depth analysis of the safety of CAR-T cell therapy for solid tumors.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant cause of morbidity associated with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. Early prediction of patients who will develop ICANS would be crucial to better guide individualized management of high-risk patients, but specific predictive markers are still missing. Serum neurofilament light chain (NfL) levels are a sensitive indicator of neuroaxonal injury in neurological diseases. Elevated NfL levels at the time of CAR T-cell infusion have been associated with the severity of ICANS, but their utility for earlier identification of patients with subclinical neurological damage has not been evaluated.We studied all consecutive adult patients who received commercial CAR T cells for relapsed/refractory B-cell lymphomas at Saint-Louis Hospital between January 2019 and February 2023. Patients with pre-existing or current neurological disease were excluded. NfL levels were quantified in frozen serum collected at the time of the decision to treat (ie, the day of leukapheresis) and at the time of treatment (ie, the day of infusion).Of the 150 study patients, 28% developed ICANS of any grade, including 15.3% of grade 2-4. Receiving a CAR construct with a CD28 domain (58% of patients) was the strongest predictor of grade 2-4 ICANS. Serum NfL levels were significantly higher in patients with grade 2-4 ICANS than in those with grade 0-1 ICANS, both at the time of leukapheresis and infusion. In multivariate models, NfL above the cut-off value was independently associated with grade 2-4 ICANS at leukapheresis (NfL>75 pg/mL, OR 4.2, 95% CI 1.2 to 14.2, p=0.022) and infusion (NfL>58 pg/mL, OR 4.3, 95% CI 1.3 to 13.7, p=0.015).In conclusion, high NfL levels at the time of the decision to proceed with CAR T-cell manufacturing may represent an early surrogate of underlying loss of neuroaxonal integrity that increases the risk of subsequent neurotoxicity. Incorporating NfL levels into the decision-making process based on each patient's risk profile could help determine the appropriate CAR product when possible, and guide the prophylactic or therapeutic management of ICANS.
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