Interference.

Top Line: Glioblastoma multiforme (GBM) has seen meaningful shifts in survival times with novel additions to the longtime paradigm such as tumor-treating fields and lomustine for MGMT-methylated tumors.

The Study: But how often have you seen these used in practice? If nothing else, that makes the newest contender more relevant as it, too, was compared to conventionally-fractionated radiation with concurrent and adjuvant temozolomide (TMZ) alone. This Chinese phase 3 trial randomized 199 patients receiving radiation and TMZ for high grade glioma to +/- the addition of none other than interferon alfa concurrent with the adjuvant TMZ phase. It was delivered at 3 million units on days 1, 3, and 5 with maintenance TMZ taken on days 2-6 every 28 days for a maximum of 12 cycles. You may remember interferon alpha as the original immunotherapy used decades ago for metastatic melanoma with preclinical studies demonstrating important implications of its use downgrading MGMT expression. Indeed, the primary endpoint of overall survival was significantly improved from a median of 19 to 27 months. As predicted, this was primarily driven by a significant improvement in median survival for MGMT-unmethylated patients (17 → 25 months).

TBL: Interferon alpha is another interesting potential addition to tried and true radiation + TMZ for high-grade glioma, particularly when MGMT is unmethylated. | Guo, JAMA Netw Open 2023