Real-World Application of PD-1 Inhibitors in High-Grade Glioma: A Case Series

Background/Objectives: Patients with high-grade glioma (HGG) have a poor prognosis despite maximal safe resection, radiotherapy, and chemotherapy, partly because of the immunosuppressive tumor microenvironment. Unfortunately, all phase III trials of anti-PD-1 therapy to date have failed to yield positive results in HGGs. Recent early-phase trials have identified promising strategies involving immune checkpoint inhibitors. Here, we share our 8-year experience with anti-PD-1 therapy in patients with HGG in a real-world setting. Methods: All patients with HGG who received PD-1 inhibitor-based therapy at our center between 2018 and 2026 were included. Medical records were reviewed longitudinally for each patient, and the latest follow-up data were collected. Patients lost to follow-up were excluded. Results: Four regimens involving anti-PD-1 treatment were identified in 22 patients with HGG (newly diagnosed = 11, recurrent = 11): (1) VEGFR-targeted therapy plus PD-1 inhibition (9 recurrent HGGs), (2) the "2-THE-TOP" regimen (tumor-treating fields plus temozolomide and PD-1 inhibitor therapy) (5 newly diagnosed HGGs), (3) anti-PD-1 monotherapy (2 recurrent and 2 newly diagnosed HGGs), and (4) neoadjuvant plus adjuvant anti-PD-1 therapy (4 newly diagnosed HGGs). Median overall survival for these four regimens was 32.7, 20.3, 28.6, and 31.8 months, respectively. No grade 3-4 treatment-related adverse events were recorded. Conclusions: Our preliminary observations suggest that PD-1 blockade may remain a viable option for patients with HGG when combined with specific therapies, administered with careful timing, and applied in selected patients.