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Abstract #0070

Ivosidenib and Vorasidenib decrease 2-hydroxyglutarate levels in low-grade glioma: an in-vivo MR Spectroscopy study

Dunja Simicic1,2, Seyma Alcicek1,3, Lindsay Blair2,4, Max Saint-Germain4,5, Helge Jörn Zöllner1,2, Christopher William Davies-Jenkins1,2, Matthias Holdhoff4,5, John Laterra4,5, Chetan Bettagowda6, Karisa Schreck4,5, Doris D. Lin1, Peter B. Barker1,2, David Olayinka Kamson4,5, and Georg Oeltzschner1,2
1Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 3Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany, 4Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 5Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 6Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, United States

Synopsis

Keywords: Tumors (Post-Treatment), Treatment Response, MRS; Low-grade glioma; IDH inhibitors; 2-hydroxyglutarate; 2-HG; 2HG; brain tumor

Motivation: IDH inhibitors are used to treat IDH-mutated cancer. MRS of the neo-onco-metabolite 2-hydroxyglutarate (2-HG) may help assess treatment efficacy.

Goal(s): To evaluate response to treatment with IDHmut-inhibiting drugs using 2-HG-optimized MRS.

Approach: 14 patients diagnosed with IDH-mutated glioma received ivosidenib or vorasidenib therapy and were scanned with optimized 1H-MRS before treatment (baseline) and repeated (follow-up) with a median on-drug follow-up of 6 months [4, 12 IQR].

Results: 2-HG estimates were substantially and significantly (p < 0.001) lower at follow-up across all included patients, independent of the tumor type or volume.

Impact: This is the first in-vivo evidence using MRS that ivosidenib/vorasidenib reduces 2-HG suggesting that in-vivo 2-HG estimates could serve as sensitive biomarkers for monitoring low-grade gliomas in vivo in response to small-molecule IDH inhibitor therapy after initiation of treatment.

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Abstract

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