Volume 30, Issue 172, June 2026

Redefining the Therapeutic Landscape of IDH-Mutant Gliomas: From Molecular Mechanisms to Clinical Application of Vorasidenib

Karolina Siemińska^1♦, Zofia Leżańska¹, Katarzyna Marcinkowska¹, Mateusz Kwiatkowski¹, Joanna Sowińska¹, Natalia Paluszkiewicz¹, Emil Pałyga¹, Aleksandra Cieślak¹, Sara Demkow¹, Sandra Bryg²

¹Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland
²Medical University of Silesia in Katowice, Józefa Poniatowskiego 15, 40-055 Katowice, Poland

^♦Corresponding author
Karolina Siemińska, Medical University of Warsaw, Żwirki i Wigury 61, 02-091 Warsaw, Poland

ABSTRACT

Introduction: The management of IDH-mutant grade 2 glioma involves a fine line between neurotoxicity and malignancy. Although the management of this type of cancer is effectively done through chemotherapy and radiotherapy, this leads to cognitive impairment; hence, there is a need for less harmful approaches. Vorasidenib represents the next-generation inhibitor of IDH1/2 that crosses into the brain and abolishes metabolic determinants of gliomagenesis. Methods: Relevant publications were retrieved from the PubMed database and discussed based on results of early trials, the pivotal Phase III INDIGO study, and neuro-oncology guidelines up until January-2026. Results: Vorasidenib inhibits D-2-HG synthesis and displays high blood-brain barrier permeability. It significantly increased median progression-free survival from 11.1 months in the placebo arm to 27.7 months (HR=0.39; p < 0.001) in the phase III INDIGO study. Vorasidenib safety appears to be good, being characterized by manageable transaminase increases, whereas issues with resistance emergence and high cost are expected. Conclusion: Vorasidenib creates a new paradigm of targeted glioma therapy. Its highly specific enzyme inhibition contributes to the retention of neurocognitive functions while delaying disease development.

Keywords: vorasidenib; IDH-mutant glioma; targeted therapy; tolerability; 2- hydroxyglutarate

Medical Science, 2026, 30, e109ms3916

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Published: 25 June 2026