Despite early reports of response to immunotherapy, a recent Phase 3 CheckMate-498 study using PD-1 blockade nivolumab in MGMT–unmethylated newly diagnosed GBM failed to meet primary endpoints (Hosea, 2019) highlighting the need to better stratify patients and identify potential responders as well as testing potential combinational therapies. The gene discussed is MGMT; the disease is glioblastoma.