Dr Bruno on Early Predictors of Vorasidenib Response in IDH-Mutant Low-Grade Glioma

“The effect of [vorasidenib] can be seen earlier if [additional] tools are used with the conventional MRI monitoring.”

Francesco Bruno, MD, PhD, a neurologist and neuro-oncologist in the Division of Neuro-Oncology in the Department of Neuroscience at the University of Turin and the City of Health and Science University Hospital, discussed findings from a prospective study of early predictors of response to vorasidenib (Voranigo) in patients with IDH-mutant grade 2 glioma, presented at the 2026 SNO Annual Meeting.

Vorasidenib can induce MRI changes that can be followed over the first 12 to 24 months, but response is often stable disease by conventional bidirectional response assessment in neuro-oncology 2.0 criteria, Bruno said. Volumetric segmentation captures faster responses, shortening the time to best response from 12 months to 6 months, while ¹⁸F-DOPA PET shows early responses within the first 3 months, he explained. In the study of 54 patients treated through an expanded access program, the objective response rate was 17.0% (median time to objective response rate [ORR], 11.5 months) with bidimensional MRI, 28.3% (median time to ORR, 5.7 months) with volumetric MRI, and 76.5% (n = 13 of 17 measurable patients; median time to ORR, 3.2 months) with ¹⁸F-DOPA PET. Layered monitoring matters, Bruno said, because low-grade glioma grows slowly and progression can occur after several years, so small changes can inform patients and physicians, particularly with a new, high-cost drug.

The investigators also focused on clinical symptoms, as patients with IDH-mutant glioma are often young and the tumor affects quality of life, family, work, and neurocognition, Bruno noted. Seizures are the main symptom, and the findings confirm exploratory analyses from the phase 3 INDIGO trial (NCT04164901) showing that vorasidenib positively affects seizures, he said. Among 12 patients with active seizures at treatment start, 11 (92%) had a seizure response, with a median time to response of 28 days (IQR, 1-2; range, 1-3). Early seizure response preceded tumor shrinkage on MRI at 3 and 6 months (P = .009 for both).Seizures are the fastest marker of response, often with seizure freedom within the first months, Bruno said, and this quicker signal helps show that the drug is actively working, he concluded.

Disclosures: Bruno reported receiving honoraria for preceptorships from Servier.