MGMT and brain neoplasm: In Checkmate-498 in exclusively unmethylated MGMT patients, nivolumab plus RT was significantly inferior to TMZ and RT in terms of OS.26 Seemingly, in Checkmate-548 in methylated MGMT patients, the addition of nivolumab to RT plus TMZ could not increase OS and PFS despite increased toxicity.27 The failure of ICIs, which is attributable to the immunologic coldness of brain tumors, have made investigators combine ICI with OV-based therapies, as described above, to see whether it can improve results.