Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab

Purpose: There is an unmet need for new treatment options and biomarkers for patients with glioblastoma (GBM). Here we investigated three non-invasive biomarkers: type VI collagen degraded by granzyme B (C4G) and matrix metalloproteases (C4M), respectively, and ADAM10-degraded Tau (Tau-A). Methods: Biomarker levels in pre- and on-treatment serum samples from patients with recurrent GBM (n = 39) treated with nivolumab and bevacizumab (NCT03890952) were compared to healthy levels (n = 22) and associated with overall survival (OS) outcome (median cutpoint). Longitudinal changes in biomarkers were investigated by a Mixed-effects analysis. Results: Tau-A (p < 0.0001) and C4G (p = 0.005), but not C4M (p = 0.106), were increased in patients. High Tau-A and C4G associated with improved OS (Tau-A: HR = 0.41, 95%CI = 0.20–0.86, C4G: HR = 0.47, 95%CI = 0.24–0.94). Only C4G increased with treatment (p = 0.024–0.005). Conclusions: Tau-A and C4G are elevated in serum from patients with recurrent GBM and prognostic for OS. If validated, these biomarkers could be applied to clinical trials.