Nevertheless, whereas IMI after only local therapy (surgery without or with radio(chemo)therapy) did not improve the median OS, and the addition of TMZ during and after radiotherapy only marginally (albeit significantly) improved median OS from 11.8 to 12.6 months [2], the major shift in median OS from 11.8 to 22.07 months when both TMZ and IMI were combined together suggests a synergy between both modes of action for the improvement of the OS of patients with MGMT promoter-unmethylated GBM patients. This evidence concerns the gene MGMT and glioblastoma.