Dataset Information

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

ABSTRACT:

Background and purpose

A real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN.

Methods

This single-center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score-clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6-12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa^® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2.

Results

Eighty-two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR-CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001).

Conclusions

A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.

SUBMITTER: Velasco R

PROVIDER: S-EPMC11295167 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Publications

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

Velasco Roser R Marco Carla C Domingo-Domenech Eva E Stradella Agostina A Santos Cristina C Laquente Berta B Ferrer German G Argyriou Andreas A AA Bruna Jordi J

European journal of neurology 20240701 9

<h4>Background and purpose</h4>A real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN.<h4>Methods</h4>This single-center prospective observational longitudinal study included patien ...[more]

PMID: 38952074

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Project description: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.

Project description:Neurofilament light chain (NfL), released during central nervous injury, has evolved as a powerful serum marker of disease severity in many neurological disorders, including infectious diseases. So far NfL has not been assessed in cerebral malaria in human or its rodent model experimental cerebral malaria (ECM), a disease that can lead to fatal brain edema or reversible brain edema. In this study we assessed if NfL serum levels can also grade disease severity in an ECM mouse model with reversible (n = 11) and irreversible edema (n = 10). Blood-brain-barrier disruption and brain volume were determined by magnetic resonance imaging. Neurofilament density volume as well as structural integrity were examined by electron microscopy in regions of most severe brain damage (olfactory bulb (OB), cortex and brainstem). NfL plasma levels in mice with irreversible edema (317.0 ± 45.01 pg/ml) or reversible edema (528.3 ± 125.4 pg/ml) were significantly increased compared to controls (103.4 ± 25.78 pg/ml) by three to five fold, but did not differ significantly in mice with reversible or irreversible edema. In both reversible and irreversible edema, the brain region most affected was the OB with highest level of blood-brain-barrier disruption and most pronounced decrease in neurofilament density volume, which correlated with NfL plasma levels (r = - 0.68, p = 0.045). In cortical and brainstem regions neurofilament density was only decreased in mice with irreversible edema and strongest in the brainstem. In reversible edema NfL plasma levels, MRI findings and neurofilament volume density normalized at 3 months' follow-up. In conclusion, NfL plasma levels are elevated during ECM confirming brain damage. However, NfL plasma levels fail short on reliably indicating on the final outcomes in the acute disease stage that could be either fatal or reversible. Increased levels of plasma NfL during the acute disease stage are thus likely driven by the anatomical location of brain damage, the olfactory bulb, a region that serves as cerebral draining pathway into the nasal lymphatics.

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Project description:Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3- to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke (n = 31), TIA (n = 9), and healthy controls (n = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.

Dataset Information

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

Background and purpose

Methods

Results

Conclusions

Publications

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

Similar Datasets

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