Serum neurofilament light chain (sNFL) as a predictive biomarker for Chemotherapy-induced peripheral neurotoxicity (CIPN): consideration of current evidence, validation steps, and barriers to CIPN biomarker implementation in clinical practice—a narrative review

Purpose: Several anticancer drugs can cause chemotherapy-induced peripheral neurotoxicity (CIPN) in approximately 70% of patients; of these, 30% continue to have chronic symptoms hampering quality of life. As more people live with and beyond cancer therapy, it is becoming increasingly important for clinicians to assess those at higher risk of CIPN and provide care for managing CIPN severity. Biomarkers could be appropriate in this regard. However, an initial step towards biomarker-informed care is to advance scientific knowledge regarding the potential of current biomarkers such as neurofilament light chain (NfL). Here, outcomes of a CIPN biomarker workshop and discussions among clinical and scientific experts held during the MASCC 2024 annual conference are reported. The aims of this work are to (1) identify knowledge gaps regarding the potential for serum NfL (sNfL) as a predictive CIPN biomarker, (2) provide guidance for future biomarker research, and (3) explore whether sNfL is ready for use in clinical practice. Methods: Consensus of the experts was gained using a Normative Group Technique. A two-stage iterative approach was used: Stage 1 involved a literature review and an in-person workshop; Stage 2 involved a virtual zoom event to confirm understanding and priorities following the workshop. Results: Eleven studies identified that increases in serum NfL after receiving 2-3 chemotherapy doses are associated with CIPN severity post treatment. Despite preliminary evidence suggesting positive correlations among sNfL and CIPN objective and subjective measures, wide variation in sNfL levels, the prescribed neurotoxic chemotherapy agent, dose and schedule, and symptom assessment time points make it difficult to use sNfL as a predictor of CIPN severity. Conclusions: While there is potential for sNfL to be a useful biomarker, larger scale research exploring the predictive value is needed before sNfL can be used to inform clinical decision-making. Identifying links with validated clinical assessments could be utilized to enhance biomarker accuracy and to address the multiple pathological mechanisms of neurotoxicity that occur from the differing chemotherapies. Moreover, workshop participants identified significant barriers to biomarker implementation (e.g. costs, long processing time, and unknown cut off points).