Utility of Vorasidenib in IDH1 R132C-Mutant WHO Grade 2 Astrocytoma: A Case Report.
6 affiliations
- 1West Virginia University School of Medicine, Morgantown, WV, USA.
- 2Department of Neurosurgery, West Virginia University School of Medicine, Morgantown, WV, USA.
- 3Department of Pathology, Anatomy and Laboratory Medicine, West Virginia University School of Medicine, Morgantown, WV, USA.
- 4Department of Neuroradiology, West Virginia University School of Medicine, Morgantown, WV, USA.
- 5Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV, USA.
- 6Department of Medical Oncology, West Virginia University School of Medicine, Morgantown, WV, USA.
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.
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BibTeX
@article{hickey2026utility,
title = {{Utility of Vorasidenib in IDH1 R132C-Mutant WHO Grade 2 Astrocytoma: A Case Report.}},
author = {Justin Hickey and Emily Pack and Denisse Arteaga and Johnie Hodge and Sanjay Bhatia and Peng Han and Parissa Feizi and Liv Miller and Sonikpreet Aulakh},
journal = {OncoTargets and therapy},
year = {2026},
month = oct,
doi = {10.2147/ott.s638827},
url = {https://europepmc.org/article/MED/42904143},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Utility of Vorasidenib in IDH1 R132C-Mutant WHO Grade 2 Astrocytoma: A Case Report.
AU - Justin Hickey
AU - Emily Pack
AU - Denisse Arteaga
AU - Johnie Hodge
AU - Sanjay Bhatia
AU - Peng Han
AU - Parissa Feizi
AU - Liv Miller
AU - Sonikpreet Aulakh
PY - 2026
DA - 2026/10/16
JO - OncoTargets and therapy
DO - 10.2147/ott.s638827
UR - https://europepmc.org/article/MED/42904143
AB - 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.
SN - 1178-6930
ER -