Utility of Vorasidenib in IDH1 R132C-Mutant WHO Grade 2 Astrocytoma: A Case Report

Abstract

Abstract WHO grade 2 astrocytomas are defined by an IDH mutation and the absence of 1p/19q codeletion. Most harbor the canonical IDH1 R132H substitution; rarer R132X variants, including R132C, remain underrepresented in prospective trials. Vorasidenib, a brain-penetrant dual IDH1/IDH2 inhibitor, prolongs progression-free survival in residual or recurrent grade 2 IDH-mutant glioma and is now included in contemporary North American guidelines when radiotherapy and chemotherapy can be deferred. We report a 25-year-old man who underwent maximal safe resection of a right temporal mass diagnosed as WHO grade 2 astrocytoma, IDH1 R132C mutant, with co-occurring ATRX and TP53 alterations. Serial postoperative MRI showed progressive residual non-enhancing T2/FLAIR signal (7 × 6 mm, then 10×7 mm, then 10×9 mm), and a 2024 biopsy confirmed residual grade 2 tumor without anaplastic features. Vorasidenib 40 mg orally once daily was started in fall 2024. After 17 months of continuous therapy (35 months after resection), the residual non-enhancing focus remains radiographically stable, and no treatment-related adverse events have occurred. Vorasidenib binds an allosteric pocket at the IDH1 dimer interface that does not directly include codon 132, which supports anticipated class activity across R132X variants. This observation is structural, not a demonstration that R132C is more sensitive than R132H. Direct comparative clinical data for R132C remain absent. This case adds real-world evidence that vorasidenib can be used safely in this uncommon molecular subgroup.