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

CNS Neurosci Ther. 2022 Oct;28(10):1476-1491. doi: 10.1111/cns.13915. Epub 2022 Jul 13.

Abstract

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.

Keywords: glioblastoma multiforme; immunotherapy; meta-analysis; predictive factor.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / therapy
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • Glioblastoma* / genetics
  • Glioblastoma* / therapy
  • Humans
  • Immunotherapy*
  • Neoplasm Recurrence, Local / genetics
  • Prognosis

Substances

  • DNA Modification Methylases