Immune checkpoint inhibitors have not demonstrated a survival benefit in unselected high-grade glioma populations; however, a subset of patients may achieve durable disease control. We report the case of a 30-year-old male patient diagnosed with a right temporoparietal high-grade glioma, initially classified as anaplastic astrocytoma and later evolving to astrocytoma, isocitrate dehydrogenase (IDH)-mutant, grade 4 according to the 2021 World Health Organization classification. The patient underwent multiple surgical resections followed by radiotherapy with concomitant temozolomide and subsequent adjuvant temozolomide (Stupp protocol). Upon disease recurrence, he received second-line treatment with lomustine plus bevacizumab, with documented progression across successive lines of therapy. In the absence of standard therapeutic options, off-label nivolumab was initiated in November 2018 following further progression. The tumor harbored an IDH1 R132H mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Corticosteroids were discontinued prior to immunotherapy initiation. Serial magnetic resonance imaging demonstrated sustained radiological stability, without evidence of nodular enhancement or increased perfusion suggestive of recurrence. The most recent imaging assessment (March 2026) confirmed ongoing disease stability of more than seven years after treatment initiation. Treatment was well tolerated, with only mild immune-related arthralgias reported. The patient remains functionally independent, with stable mild residual hemiparesis. This case highlights the potential for prolonged disease stability under anti-Programmed cell death protein 1 (PD-1) therapy in selected patients with high-grade glioma. Although immunotherapy has not shown benefit in unselected populations, molecular features such as IDH mutation and MGMT promoter methylation, as well as the absence of corticosteroid use, may contribute to enhanced treatment responsiveness and warrant further investigation.
Santos et al. (Tue,) studied this question.