Open questions on vorasidenib

Purpose of review Vorasidenib has demonstrated efficacy in isocitrate dehydrogenase (IDH)-mutant grade 2 gliomas that do not require immediate oncological treatment. Here, we summarize open questions regarding its long-term benefit, its optimal use in IDH-mutant grade 2 gliomas as well as its potential use in grade 3 and 4 IDH-mutant gliomas. Recent findings In IDH-mutant grade 2 gliomas, vorasidenib may act as a differentiation therapy. Updated results from the INDIGO trial suggest an additional effect on seizure control. Volumetric analysis and amino acid PET imaging may improve response assessment. However, long-term follow-up and new clinical trials will be needed to determine whether first-line vorasidenib preserves cognition, quality of life and improves overall survival. Since contrast-enhancement rather than histological grade appears to be more closely associated with disease control, selected grade 3 IDH-mutant gliomas might also benefit from first-line vorasidenib. Ongoing trials are evaluating vorasidenib as maintenance therapy after radiochemotherapy, and in association with chemotherapy and different immunotherapies. Summary While vorasidenib is becoming the first-line treatment in the majority of IDH-mutant grade 2 gliomas, we are progressively learning how it works, how it should be used and in which contexts beyond grade 2 IDH-mutant gliomas it could be beneficial.