Impact of molecular and clinical variables on survival outcome with immunotherapy for glioblastoma patients: A systematic review and meta‐analysis

BACKGROUND: Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno‐oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors. METHODS: A quantitative meta‐analysis was conducted using the random‐effects model. Several potential factors were also reviewed qualitatively. RESULTS: A total of 39 clinical trials were included after screening 1317 papers. Patients with O6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression‐free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death‐ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non‐immunotherapy. CONCLUSION: Several factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker‐driven prospective studies are warranted.