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

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.