Prognostic Utility of Histology and Idh-mutation Status for Immunotherapy Response in High Grade Glioma: A Hazard Meta-analysis

Introduction: The survival and treatment response of immunotherapy (IT) in World Health Organization Grade III (G3) glioma or IDH mutation (IDHmt) glioma is understudied, as most research has focused on glioblastoma and IDH-wild type (IDHwt) tumors.

Methods: A systematic literature search was conducted in PubMed, Google Scholar, Cochrane, and Scopus databases following PRISMA guidelines. A random-effects meta-analysis was performed, with the primary endpoint being overall mortality.

Results: From 1223 studies, 21 studies involving 207 patients with Grade III glioma and 11 studies with 82 patients with IDHmt glioma were included. Patients received treatments including tumor vaccines (15 studies: 89 G3, 17 IDHmt), immune checkpoint inhibitors (2 studies: 1 G3, 39 IDHmt), oncolytic viruses (7 studies: 16 G3, 20 IDHmt), and radioimmunotherapy (8 studies: 101 G3, 6 IDHmt). Grade III tumors were predominantly anaplastic astrocytoma (155/207, 72.2%, 95% CI: 62.64-81.76) and anaplastic oligodendroglioma (33/207, 15.95%, 95% CI: 8.55-23.35). The mean overall survival from IT administration was 28.8 months (95% CI: 15.38-42.13) for newly diagnosed Grade III tumors and 56.7 months (95% CI: 48.25-65.15) for newly diagnosed IDHmt glioma. For recurrent cases, mean progression-free survival post-IT was 5.4 months (95% CI: 4.09-6.72) in Grade III tumors and 6.9 months (95% CI: 2.07-11.76) in IDHmt tumors. Across studies, the hazard ratio for overall mortality in Grade III tumors compared to glioblastoma under the same IT protocol was 0.37 (71/207, 95% CI: 0.17-0.79, p< 0.01), and 0.23 (28/43, 95% CI: 0.05-1.07, p=0.06) comparing IDHmt to IDHwt glioma.

Conclusion : This is the first comprehensive meta-analysis to examine immunotherapy in Grade III and IDH-mutant glioma, indicating longer survival after immunotherapy than IDH-wt glioma and glioblastoma.