The role of vorasidenib, a dual inhibitor of the mutant IDH1 and IDH2 enzymes, in the treatment of diffuse adult-type gliomas

Oncology in Clinical Practice · Published 2026-01-15 · DOI 10.5603/ocp.110138

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Abstract

Diffuse gliomas (DG) constitute a complex group of the most common primary brain tumors in adults. A key mutation, present in about 80% of low-grade gliomas, is the isocitrate dehydrogenase (IDH) gene mutation, the mutant IDH (IDHmut) produces the oncometabolite D-2-hydroxyglutarate, resulting in alterations in the ge­nome-wide methylation profile, metabolic alterations, tumorigenesis, microenvironmental changes and immuno­suppression. The aim of this review was to discuss the molecular biology of IDHmut DG and present the results of the registration study of the first IDH1/2 inhibitor — vorasidenib. Given that vorasidenib is a newly registered drug, literature using PubMed and Google Scholar was reviewed. In addition to preclinical studies, results from the INDIGO study and preliminary results of vorasidenib use in clinical practice were found. INDIGO showed a significant prolongation of progression-free survival (PFS) and delayed the need for further therapies in patients with IDH-mutant gliomas treated with vorasidenib monotherapy. Further analyses revealed health-related quality of life, neurocognitive stabilization, controlled seizures, significant decrease in tumor growth rate, and a meas­urable radiographic response. Real-world studies confirmed the drug’s effectiveness in a broader population. The result of a study evaluating the combination of this drug with an immune checkpoint inhibitor is expected in 2027. In conclusion, vorasidenib significantly prolongs PFS in IDHmut low-grade gliomas; its efficacy in other settings requires further investigation.

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Year
2026

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