Ivosidenib and Vorasidenib Decrease Intratumoral 2-Hydroxyglutarate and Total Choline Levels in Patients with...

Area of Science:

• Neuro-oncology
• Molecular Diagnostics
• Medical Imaging

Background:

• IDH-mutant gliomas are characterized by the oncometabolite 2-hydroxyglutarate (2HG), a potential therapeutic target.
• Targeted therapies like ivosidenib and vorasidenib aim to suppress 2HG production in IDH-mutant gliomas.
• Non-invasive monitoring of treatment response is crucial for managing these slow-growing tumors.

Purpose of the Study:

• To evaluate the utility of in-vivo magnetic resonance spectroscopy (MRS) for monitoring treatment response in IDH-mutant gliomas.
• To assess if MRS-measured 2-hydroxyglutarate (2HG) levels correlate with treatment efficacy of IDH inhibitors.
• To relate changes in 2HG levels to alterations in tumor volume assessed by MRI.

Main Methods:

• 18 patients with IDH-mutated gliomas received ivosidenib or vorasidenib therapy.
• Pre-treatment and follow-up MRI/MRS scans using 2HG-optimized PRESS were performed.
• Median on-drug follow-up was 4.3 months, with 14 patients passing quality control.

Main Results:

• A significant decrease in 2HG levels was observed across all patients (p < 0.001).
• Levels of total choline (tCho) and glutamine also significantly decreased (p < 0.01).
• Volumetric MRI indicated tumor growth arrest, with a modest average decrease in tumor size.

Conclusions:

• MRS detection of 2HG reduction is a promising non-invasive method for monitoring IDH inhibitor therapy.
• Early decreases in tumor 2HG and tCho levels suggest treatment effectiveness.
• MRS may serve as a valuable tool for assessing treatment response in lower-grade gliomas.