Blood group O attributes to prolonged progression-free survival, overall survival, and 5-year survival in isocitrate dehydrogenase-wildtype glioblastoma patients with MGMT promoter methylation

Background. Glioblastoma (GBM) remains incurable despite multimodal therapeutic approaches. Here, we assessed the relevance of ABO blood groups for progression-free survival (PFS), overall survival (OS), and long-term survival in a large cohort of isocitrate dehydrogenase (IDH)-wildtype (wt) GBM patients. Methods. Consecutive GBM patients (2009-2020) at a large tertiary brain tumor center were included, and clinical data were retrospectively abstracted. We dichotomized patients into those with blood group O and those with a Non-O blood group. Patient, tumor, and treatment characteristics were compared between these groups. Association with outcomes was assessed in univariable and multivariable settings via log-rank tests and Cox proportional hazards regressions, respectively. Results. Five hundred fifty-four GBM IDH-wt had available ABO information. There were no substantial differences in patient, tumor, or treatment characteristics between group O and group Non-O. In contrast, blood group O patients showed increased PFS, OS, and 5-year survivals in both univariable and multivariable analyses. Differences were strongly pronounced in patients with MGMT promoter methylated tumors receiving standardized radiochemotherapy (OS blood group O 24.6 months [95%CI 17.8-31.4] vs Non-O 17.7 months [14.1-21.3], P = .015 log-rank analysis, hazard ratio 0.70 [95%CI 0.53-0.94]), but not apparent in MGMT promoter unmethylated tumors and in patients without (standardized) adjuvant therapy. Conclusion. Blood group O status in conjunction with MGMT promoter methylation (including weak methylation) is an independent favorable prognostic marker in GBM IDH-wt patients receiving standardized radiochemotherapy. This finding is unprecedented, suggesting a linkage between the downregulation of a DNA repair protein and the absence of a functional blood cell surface glycosyltransferase.