Single-Center Experience With Vorasidenib in Patients With Grade 3 or 4 IDH-Mutant Gliomas

BACKGROUND

Vorasidenib is an IDH inhibitor approved for the treatment of grade 2 IDH-mutant gliomas but remains investigational for higher-grade tumors. We evaluated clinical experience with the agent in the setting of IDH-mutant high-grade glioma.

METHODS

Single-center retrospective review of patients with grade 3 or 4 IDH-mutant gliomas treated with vorasidenib between September 1, 2024, and December 31, 2025.

RESULTS

Fifty-six patients (median age, 41 years; range, 21-79 years; 48.2% female) were evaluated. Tumor types included grade 3 oligodendroglioma (15, 27%), grade 3 astrocytoma (27, 48%), and grade 4 astrocytoma (14, 25%). Prior treatments included surgical resection (47, 84%), radiation (45, 80%), temozolomide (44, 78%), ivosidenib (13, 23%), bevacizumab (11, 20%), lomustine (10, 18%), lomustine plus procarbazine (7, 13%), and pembrolizumab (4, 7%). The median number of prior lines of systemic therapy was 2 (range, 0-7). Eight patients (14%) were naive to systemic treatment at the time of vorasidenib initiation. The 6- and 12-month progression-free survival (PFS) rates were 66% (95% CI, 53.4%-80.4%) and 53% (95% CI, 39.2%- 71.4%), whereas the 6- and 12-month overall survival (OS) rates were 94% (95% CI, 87.2%-100.0%) and 86% (95% CI, 75.5%-97.2%), respectively. Thirty-three (58.9%) patients were still on vorasidenib at the time of last follow-up. For patients with disease progression, the median duration of vorasidenib was 118 days (range, 19-442). Forty-five (81.8%) patients had contrast enhancement at the time of vorasidenib initiation. For these patients, the 6-month PFS rate was 64% (95% CI, 51.4%-80.8%). The six-month PFS rates per prior lines of therapy were as follows: no prior systemic therapy (87.5%) vs 1 prior systemic therapy (85.7%) vs more than 1 prior systemic therapy (58.8%). Two patients required dose reductions due to toxicity (fatigue, n=1; transaminitis, n=1), and 1 patient discontinued vorasidenib due to toxicity (muscle pain, n=1).

CONCLUSIONS

In this heavily pretreated cohort of patients with high-grade IDH-mutant gliomas, vorasidenib was well tolerated and associated with promising 6- and 12-month PFS rates. The optimal role of the agent in the treatment of high-grade gliomas requires prospective evaluation.