Neurofilament Light Chain: A Potential Biomarker for Chemotherapy Induced Peripheral Neuropathy in Pediatric Adolescent Young Adults

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common treatment side effect in both pediatric and adolescent young adult patients (AYAs). CIPN causes significant clinical challenges resulting in chemotherapy dose reductions in attempt to improve painful symptoms, and additionally can result in decreased health-related quality of life and potentially impacting disease outcomes. CIPN detection in children and AYAs is a challenge, and current tools for CIPN detection rely on moderate to severe CIPN phenotypes in patients >12 years of age, with no patient reported outcomes (PROs) validated for younger children. Earlier, more sensitive tools for CIPN detection are need for younger patients. Neurofilament light chain (NF-L) is an emerging biomarker that has shown correlation with axonal damage in rat models, with the potential to serve as an early and sensitive biomarker of CIPN. This pilot study aimed to describe changes in NF-L in children and AYAs with CIPN.

Methods: This single-center, prospective study examined patients aged >10 years with leukemia or lymphoma who received a backbone chemotherapy regimen which included a tubulin toxin. CIPN was assessed by PROs with the FACT-GOG-ntx. Outcomes were evaluated at baseline prior to chemotherapy, day 1 of each chemotherapy cycle, and 6-12 weeks after last dose of chemotherapy. Values were reported as the Normalized Protein eXpression (NPX) per OLINK standard reporting on a log2. Negative N-FL values were excluded from percent change calculations. Values were calculated at baseline, first follow up, and at 90 days or the closest visit to 90 days.

Results: A total of 11 participants (aged 12-24 years) who received tubulin toxin chemotherapy backbones including to treat B-lymphoblastic leukemia (n=3), Hodgkin lymphoma (n=7), and mature B-cell lymphoma (n=1) were analyzed. 10 participants had a median % change in baseline NF-L of 67.94%. Mean NF-L levels increased from baseline timepoint (mean 2.32, median 2.16) to time point 2 (mean= 3.28, median 3.47) and remained increased at the follow-up visit closest to 90 days (mean 3.85, median 4.38). All participants had CIPN as evidenced by FACT-GOG-ntx scores, with majority of scores changing overtime from timepoint 1 (mean=1.27, median=0) to timepoint 2 (mean=3.55, median=3.00).

Conclusions: We report the first investigation of N-FL in the pediatric and AYA cancer setting as a potential novel biomarker for early and sensitive CIPN detection. These results are hypothesis generating and serve as the foundation for larger, future studies to continue investigating N-Fl as an early and objective detection measure of CIPN in this unique patient population.

Orgel:Jazz Pharma: Consultancy. Roth:Pfizer: Research Funding.