Longitudinal plasma neurofilament light chain and patient-reported outcomes as complementary markers of vincristine-associated peripheral neuropathy in adults with lymphoma: a cohort study

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurotoxicity of cancer treatment with limited diagnostic, monitoring, and treatment options. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released during neuroaxonal injury and a promising biomarker of CIPN, but prospective evidence for NfL as a marker of CIPN from vincristine-containing lymphoma chemotherapy treatment remains limited. To fill this gap, we conducted a pragmatic single-center prospective observational cohort study of adults with non-Hodgkin lymphoma (NHL) receiving first-line vincristine-containing chemotherapy to evaluate NfL dynamics across multiple pre-cycle visits and assess relationships with patient-reported and clinician-graded neuropathy measures. We followed 25 participants during 4-6 months of chemotherapy, and a small subset of those participants (n=6) for 24-42 months post-chemotherapy. Serial plasma NfL was measured and CIPN symptoms were assessed using patient- and clinician-reported measures. Longitudinal changes were analyzed using mixed-effects models. Plasma NfL increased relative to pre-cycle1 at all timepoints (all p<0.001), increasing approximately fourfold by pre-cycle4. Patient-reported CIPN scores and clinician-graded neuropathy also increased during treatment. Exploratory pooled visit-level analyses showed a modest NfL-CIPN association (repeated measures correlation=0.439, p=0.020), while timepoint-specific, lagged, and post hoc sensitivity analyses suggested potential to predict persistent CIPN symptoms from early NfL concentrations. To our knowledge, these findings extend prospective evidence supporting NfL as a biomarker of vincristine exposure in adults with NHL receiving vincristine-containing therapy and may complement patient-reported symptom assessment, clinician grading, and dose-modification context in future CIPN monitoring studies.