The Study: This study of 411 patients with grade 2 or 3 glioma with known IDH status, 1p/19q codeletion status, and MGMT methylation status sought to determine if the same holds true for grade 2 and 3 gliomas. The goal of the study was to determine if MGMT methylation status was prognostic of survival in the setting of known molecular prognostic markers. 32.8% were IDH-wild type, 36.3% were IDH-mutated, non-codeleted, and 30.9% were IDH-mutated and 1p/19q codeleted. In each of those groups, 41%, 53%, and 74%, respectively, were MGMT methylated. Among the 288 patients (70%) who were treated with alkylating chemotherapy, MGMT methylation was associated with higher median PFS (68 v 30 months) and OS (137 v 61 months). Among the remaining patients not treated with alkylating chemotherapy, MGMT methylation was not associated with survival. For the subset with IDH-mutated, 1p/19q codeleted tumors, MGMT methylation was associated with improved PFS (11.4 v 5.5 years) and OS (21.1 v 11.3 years). In the IDH-wild type subset, MGMT methylation was associated with improved PFS (18 v 9.8 mo) but not OS. And for IDH-mutated, non-codeleted tumors, MGMT methylation was wasn’t associated with PFS or OS. As we can see, the associations between MGMT methylation and survival were not consistent across subgroups, and there was strong interaction between methylation status and chemotherapy receipt in predicting survival. As a result, this editorial questions whether MGMT is an independent molecular prognostic factor of survival for grade 2 and 3 gliomas.
TBL: MGMT methylation status is associated with survival outcomes for IDH-mut, 1p/19q codeleted and IDH-wt gliomas treated with alkylating chemotherapy. | Kinslow, JAMA Oncol 2023