Blood Adv. 2022 Jan 18:bloodadvances.2021006144. doi: 10.1182/bloodadvances.2021006144. Online ahead of print.
ABSTRACT
Antitumor therapy with CD19-targeted chimeric antigen-receptor-modified T (CAR T) cells is highly efficient. However, treatment is often complicated by a unique profile of unpredictable neurotoxic side effects of varying degrees known as immune effector cell-associated neurotoxicity syndrome (ICANS). Here, in 96 patients receiving CAR T-cells for refractory B-cell malignancies at two major CAR T-cell centers, we examined whether serum levels of neurofilament light chain (NfL), a marker of neuroaxonal injury, correlate with the severity of ICANS. Serum NfL levels were measured before and after infusion of CAR T cells using a single-molecule enzyme-linked immunosorbent assay and correlated with the severity of ICANS. Elevated NfL serum levels prior to treatment were associated with more severe ICANS, in both unadjusted and adjusted analyses (p<0.01). Multivariate statistical models revealed a significant increase in NfL levels after CAR T-cell infusion (p<0.05), which correlated with the severity of ICANS (p<0.001). Pre-existing neuroaxonal injury, characterized by higher NfL levels before CAR T-cell treatment, correlated with the severity of subsequent ICANS. Thus, serum NfL level might serve as a predictive biomarker for assessing the severity of ICANS and for improving patient monitoring following CAR T-cell transfusion. However, these preliminary results should be validated in a larger prospective cohort of patients.
PMID:35042236 | DOI:10.1182/bloodadvances.2021006144
