Targeted therapies in IDH-mutant glioma: Redefining the therapeutic landscape and implications in the clinic
S. Vineeth Kumaar, Pankaj Kumar Panda, Rakesh JalaliAbstract
Background:
The isocitrate dehydrogenase (IDH) mutation serves as an early oncogenic event in IDH-mutant gliomas. Recognition of IDH mutation as a key oncogenic driver has led to the development of targeted therapies such as IDH inhibitors. The standard of care for gliomas incorporates surgery, radiotherapy, and chemotherapy. The treatment of IDH-mutant glioma is currently undergoing a paradigm shift after the results of the Investigating Vorasidenib in Glioma (INDIGO trial), which introduced the use of targeted therapy.
Recent Development:
Efforts to inhibit mutant IDH activity, which is the key driver mutation in glioma genesis, led to the development of targeted therapies. Vorasidenib is a recently developed oral brain-penetrant dual inhibitor of mutant IDH1 and IDH2 approved by the Food and Drug Administration. This is a biologically directed treatment for grade 2 IDH-mutant astrocytoma and oligodendrogliomas after surgery. This phase III INDIGO trial demonstrated significant improvement in progression-free survival and delayed time to next intervention as compared to placebo in asymptomatic patients with residual or recurrent grade 2 IDH-mutant gliomas.
Low- and Middle-Income Countries/India Relevance:
For India and other low- and middle-income countries, vorasidenib raises both opportunity and complexity. It may defer radiotherapy and chemotherapy in selected patients. This will require reliable molecular diagnostics, longitudinal magnetic resonance imaging surveillance, affordability strategies, and careful integration into multidisciplinary neuro-oncology pathways. India received the Central Drugs Standard Control Organization marketing authorization for vorasidenib in December 2025, making this discussion directly relevant to the Indian scenario.
Conclusion:
This review will examine biological rationale, clinical evidence, patient selection, safety, sequencing, unresolved questions, and implementation priorities for equitable adoption.