Neoadjuvant Triplet Immune Checkpoint Blockade in Newly Diagnosed Glioblastoma

Abstract 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 low1,2. Anti-PD-1 ICI monotherapy administered post-primary resection or after recurrence has not improved GBM outcomes3,4. 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.