Viral and other therapies for recurrent glioblastoma: is a 24-month durable response unusual?

Abstract

A phase I trial of an engineered poliovirus for the treatment of recurrent glioblastoma (GBM) has attracted attention due to 8 survivors reaching the 24-month and 5 reaching the 36-month survival landmarks.1 Genetically engineered viruses (oncolytic viruses) have been in trials for GBM for almost two decades.2 These replication-competent (tumor-selective, oncolytic, replication-conditional) viruses or replication-defective viral vectors (gene therapy) deliver cytotoxic payloads to tumors, leading to immunogenic death and intratumoral inflammatory responses. This transforms the tumor microenvironment from immunologically naïve ( cold ) to inflamed ( hot ), increasing immune cell recognition of tumor antigens and the durable responses observed in virotherapy.3,4 Several current and past virotherapy trials have reported a tail of apparent responders at the 24-month landmark. Other modalities have also reported a tail of seemingly long-term survivors. These trials seem to show that these responder tails characterize a defined subset of GBM patients.