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

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 naive (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.