Neoadjuvant Triplet Immune Checkpoint Blockade in Newly Diagnosed Glioblastoma
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Glioblastoma (GBM) is an aggressive primary brain tumor with a dismal prognosis. Given the paucity of tumor infiltrating lymphocytes (TILs), an immune suppressive tumor microenvironment and a low tumor mutation burden, the potential benefits of immune checkpoint inhibition (ICI) for GBM patients are considered low 1,2 . Anti-PD-1 ICI monotherapy administered post-primary resection or after recurrence has not improved GBM outcomes 3,4 . Here, we present the first case of newly diagnosed IDH-wildtype, MGMT -unmethylated GBM treated with upfront neoadjuvant triplet ICI (anti-PD-1/anti-CTLA4/anti-LAG3). Twelve days post-therapy, the primary resected GBM showed anti-PD-1-bound TILs and marked TIL infiltration and activation, compared with baseline biopsy. After 10 months, there is no recurrence.
