Redefining Care for IDH-Mutant Low-Grade Gliomas: Clinical Implications of the INDIGO Trial and Updated Guidelines

Pathogenic variants in the genes encoding isocitrate dehydrogenase (IDH1 and IDH2) are the defining driver mutations in diffuse low-grade gliomas. When IDH is mutated, the production of the oncometabolite 2-hydroxyglutarate triggers downstream metabolic changes that promote gliomagenesis. The identification of the isocitrate dehydrogenase mutation (mIDH) in diffuse gliomas has not only redefined prognosis but also treatment for patients with these tumours. With the identification of the IDH mutation, targeted therapies have emerged as a promising therapeutic strategy in gliomas. The INDIGO trial compared the IDH inhibitor vorasidenib to a placebo. Progression-free survival (PFS) and time to next intervention were extended in patients who received vorasidenib vs. placebo. The side-effect profile was tolerable compared to that of traditional cytotoxic chemotherapies. In August 2024, vorasidenib received FDA approval for the treatment of grade 2 mIDH gliomas and is included in the National Comprehensive Cancer Network Guidelines for central nervous system tumours.