In a study reported in JAMA Oncology, Kinslow et al found that MGMT promoter methylation (mMGMT) was associated with improved survival outcomes in patients receiving alkylating chemotherapy for low-grade and anaplastic gliomas.
Study Details
The study involved 411 patients with grade II or III gliomas from three prospective cohort studies (MSK-IMPACT, EORTC 26951, and Columbia University) with data collected between August 1995 and August 2022.
Key Findings
Of the 411 patients, 229 had mMGMT and 182 had unmethylated MGMT promoter status (uMGMT). Alkylating chemotherapy was received by 288 patients overall, including 69% of the mMGMT group and 72% of the uMGMT group.
mMGMT was found in 56 (42%) of 135 patients with IDH wild-type gliomas, 79 (53%) of 149 with IDH-mutant and noncodeleted gliomas, and 94 (74%) of 127 with IDH-mutant and 1p/19q-codeleted gliomas.
On multivariate analysis among patients who received chemotherapy, median progression-free survival was 30 months (95% confidence interval [CI] = 15–54 months) in the uMGMT group vs 68 months (95% CI = 54–132 months] in the mMGMT group (adjusted hazard ratio [aHR] = 1.95, 95% CI = 1.39–2.75, P < .001). Median overall survival was 61 months (95% CI = 47–97 months) in the uMGMT group vs 137 months (95% CI = 104 months to not reached) in the mMGMT group (aHR = 1.65, 95% CI = 1.11–2.46, P = .01).
Among patients receiving chemotherapy, adjusted hazard ratios for uMGMT vs mMGMT were 2.15 (P = .005) for progression-free survival and 1.69 (P = .06) for overall survival among patients with IDH wild-type gliomas and 2.99 (P = .003) and 4.21 (P = .02), respectively, among patients with IDH-mutant and codeleted gliomas. No significant differences on univariate analysis were observed among patients with IDH-mutant and noncodeleted gliomas for progression-free survival (HR = 1.19, P = .56) or overall survival (1.07, P = .85); the subgroup thus was not included in multivariate analysis.
In analysis adjusting for clinical factors, uMGMT status was associated with:
- Poorer progression-free survival (aHR = 2.15, P = .005) and overall survival (aHR = 1.69, P = .06) among patients with IDH wild-type gliomas
- Poorer progression-free survival (aHR = 2.99, P = .003) and overall survival (aHR = 4.21, P = .02) among patients with IDH-mutant and codeleted gliomas
- No significant difference in progression-free survival (aHR = 1.19, P = .56) or overall survival (aHR = 1.07, P = .85) among those with IDH-mutant and noncodeleted gliomas.
Among patients who did not receive chemotherapy, mMGMT status was not associated with progression-free survival or overall survival.
The investigators concluded, “This study suggests that mMGMT is associated with response to alkylating chemotherapy for low-grade and anaplastic gliomas and may be considered as a stratification factor in future clinical trials of patients with IDH wild-type and IDH-mutant and codeleted tumors.”
Tony J.C. Wang, MD, of the Department of Radiation Oncology, Columbia University Irving Medical Center, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by a grant from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
