Analysis Of Mgmt Promoter Methylation In Malignant Gliomas

Testing for O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation has been proposed as a method to predict which patients with malignant gliomas may benefit from the use of alkylating agent chemotherapy, such as temozolomide (TMZ). Malignant gliomas are often treated with combined therapy, including resection, chemotherapy, and radiotherapy. However, combined therapy may be too intense in the elderly population, in whom these tumors are most commonly seen. The following conclusions are based on a review of the evidence, including but not limited to published evidence and clinical expert opinion, solicited via BCBSA's Clinical Input Process. For individuals who have high-grade glioma(s) who receive MGMT promoter methylation testing, the evidence includes cohort studies of prognosis, studies nested within randomized trials, and treatment trials that selected subjects based on MGMT methylation status. Relevant outcomes include overall survival, disease-specific survival, test accuracy, and changes in disease status. While there are no studies directly evaluating whether the use of MGMT methylation testing improves patient outcomes, MGMT status is consistently associated with outcomes of glioma patients. Data from randomized controlled trials have shown that MGMT promoter methylation is predictive for response to alkylating chemotherapeutic agents such as TMZ. The response rate and overall survival with the use of TMZ are higher in patients who have MGMT promoter methylation. While TMZ offers some benefit regardless of MGMT methylation status, studies have consistently suggested that MGMT methylation identifies patients who are more likely to benefit from TMZ. TMZ combined with radiotherapy remains the standard of care for most patients. TMZ is associated with a modest increase in hematologic adverse events compared with radiotherapy alone. Counseling about risks and benefits in a patient with comorbidities may result in a choice to avoid TMZ when that patient is less likely to benefit from the treatment. The published evidence supports a meaningful improvement in the net health outcome. Evidence reported through clinical input further supports that this use provides a clinically meaningful improvement in net health outcome and is consistent with generally accepted medical practice. Patient selection criteria for MGMTgene promoter from glioma tumor tissue include the following criteria: (1) have a tumor type consistent with high-­grade malignant glioma (eg, glioblastoma multiforme, anaplastic astrocytoma); and (2) candidate for temozolomide therapy or radiotherapy; and (3) methylation results will be used to direct therapy choices. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.