To characterize the types, frequencies, grades, and severities of treatment-related adverse events reported in clinical trials of oncolytic virus therapies for primary CNS tumors.

While current treatments for primary CNS tumors remain limited, oncolytic virus therapies are emerging as new approaches that selectively target and destroy tumor cells. However, data on treatment-related adverse events are scattered.

Following PRISMA guidelines, a systematic review of seventeen publications on oncolytic virus clinical trials indexed in PubMed up to October 2023 was conducted. Treatment-related adverse events were extracted and analyzed by type, frequency, and Common Terminology Criteria for Adverse Events (CTCAE) grade. Severe adverse events were defined as a CTCAE grade of 3 or higher.

Neurological adverse events accounted for 260 out of 533 total adverse events (49%). The five most common neurological adverse events were headache (n = 60, 7% severe), seizure (43, 23% severe), hemiparesis (37, 35% severe), cerebral edema (33, 48% severe), and dysphasia (26, 0% severe). Common non-neurological adverse events included fever (n = 58, 5% severe), vomiting (32, 6% severe), nausea (30, 0% severe), fatigue (26, 0% severe), and decreased lymphocyte count (12, 58% severe). Severe events comprised 22% (58/260) of neurological and 9% (25/273) of non-neurological adverse events. Overall, severe adverse events were not common (83/533, 16%). Among individual therapies, DNX-2401 (adenovirus) had the highest total rate of severe adverse events (31/123, 25%), while G207 (HSV-1) had the highest rate of severe neurological adverse events (11/16, 69%).

Early clinical trials of oncolytic virus therapies demonstrated a tolerable safety profile, with severe adverse events occurring in only 16% of the cases. Neurological events made up nearly half of all adverse events and may warrant careful monitoring due to their higher severity rates, observed particularly in hemiparesis and cerebral edema.