New Biomarker Detects Chemotherapy-Related Neurotoxicity

MONTREAL — Levels of neurofilament light chain (Nfl) may be a biomarker of chemotherapy-induced peripheral neurotoxicity (PIPN), new research suggests.

Investigators found Nfl levels increased in cancer patients following a first infusion of the medication paclitaxel and corresponded to neuropathy severity 6 to 12 months post-treatment, suggesting the blood protein may provide an early PIPN biomarker.

“Nfl after a single cycle could detect axonal degeneration,” said lead investigator Masarra Joda, a researcher and PhD candidate at the University of Sydney in Australia. He added that “quantification of Nfl may provide a clinically useful marker of emerging neurotoxicity in patients vulnerable to PIPN.”

The findings were presented June 24 at the Peripheral Nerve Society (PNS) 2024 Annual Meeting.

Common, Burdensome Side Effect

A common side effect of chemotherapy CIPN manifests as sensory neuropathy and causes degeneration of the peripheral axons. A protein biomarker of axonal degeneration, Nfl has previously been investigated as a way of identifying patients at risk of CIPN.

The goal of the current study was to identify the potential link between Nfl with neurophysiological markers of axon degeneration in patients receiving the neurotoxin chemotherapy paclitaxel.

The study included 93 cancer patients. All were assessed at the beginning, middle, and end of treatment. CIPN was assessed using blood samples of Nfl and the Total Neuropathy Score (TNS), the Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale and patient-reported measures using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire—Chemotherapy-Induced Peripheral Neuropathy Module (EORTC-CIPN20).

Axonal degeneration was measured with neurophysiological tests including sural nerve compound sensory action potential (CSAP) for the lower limbs, and sensory median nerve CSAP, as well as stimulus threshold testing for the upper limbs. 

Almost all of study participants (97%) were female. The majority (66%) had breast cancer and 30% had gynecological cancer. Most (73%) were receiving a weekly regimen of paclitaxel, and the remainder were treated with taxanes plus platinum once every 3 weeks. By the end of treatment, 82% of the patients had developed PIPN, which was mild in 44%, and moderate/severe in 38%. 

Nfl levels increased significantly from baseline to after the first dose of chemotherapy (P <.001 that="" nerve="" damage="" occurs="" from="" the="" very="" beginning="" of="" treatment="" senior="" investigator="" susanna="" park="" phd="" told="">Medscape Medical News. 

In addition, “patients with higher Nfl levels after a single paclitaxel treatment had greater neuropathy at the end of treatment (higher EORTC scores [P ≤ 0.026], and higher TNS scores [P ≤.00]),” added Park, who is associate professor at the University of Sydney.

“Importantly, we also looked at long-term outcomes beyond the end of chemotherapy, because chronic neuropathy produces a significant burden in cancer survivors,” said Park. 

” Among a total of 44 patients who completed the 6- to 12-month post-treatment follow-up, NfL levels after a single treatment were linked to severity of nerve damage quantified with neurophysiological tests, and greater Nfl levels at mid-treatment were correlated with worse patient and neurologically graded neuropathy at 6-12 months.”

Park said the results suggest that NfL may provide a biomarker of long-term axon damage and that Nfl assays “may enable clinicians to evaluate the risk of long-term toxicity early during paclitaxel treatment to hopefully provide clinically significant information to guide better treatment titration.” 

Currently, she said, CIPN is a prominent cause of dose reduction and early chemotherapy cessation. 

“For example, in early breast cancer around 25% of patients experience a dose reduction due to the severity of neuropathy symptoms.” But, she said, “there is no standardized way of identifying which patients are at risk of long-term neuropathy and therefore, may benefit more from dose reduction. In this setting, a biomarker such as Nfl could provide oncologists with more information about the risk of long-term toxicity and take that into account in dose decision-making.” 

For some cancers, she added, there are multiple potential therapy options.

“A biomarker such as NfL could assist in determining risk-benefit profile in terms of switching to alternate therapies. However, further studies will be needed to fully define the utility of NfL as a biomarker of paclitaxel neuropathy.” 

Promising Research

Commenting on the research for Medscape Medical News, Maryam Lustberg, MD, associate professor, director of the Center for Breast Cancer at Smilow Cancer Hospital, and Yale Cancer Center, and chief of Breast Medical Oncology at Yale Cancer Center, in New Haven, Connecticut, said the study “builds on a body of work previously reported by others showing that neurofilament light chains as detected in the blood can be associated with early signs of neurotoxic injury.” 

She added that the research “is promising, since existing clinical and patient-reported measures tend to under-detect chemotherapy-induced neuropathy until more permanent injury might have occurred.” 

Lustberg, who is immediate past president of the Multinational Association of Supportive Care in Cancer, said future studies are needed before Nfl testing can be implemented in routine practice, but that “early detection will allow earlier initiation of supportive care strategies such as physical therapy and exercise, as well as dose modifications, which may be helpful for preventing permanent damage and improving quality of life.” 

The investigators and Lustberg report no relevant financial relationships.