The striking reductions in tumor 2HG and tCho levels early following initiation of targeted therapy using an IDH inhibitor suggest that MRS may provide an important tool for monitoring treatment response of lower-grade gliomas.

Therapeutic advances are highlighted, with particular emphasis on brain-penetrant IDH inhibition (vorasidenib) and on emerging strategies including vaccines, checkpoint combinations, epigenetic modulation, metabolic and microenvironment targeting, and novel delivery platforms...Finally, future directions in trial design, survivorship-oriented endpoints, and biomarker-driven monitoring are outlined. A trajectory-based paradigm is emphasized in which neurocognitive preservation, time to radiotherapy or chemotherapy, and patient-reported outcomes are prioritized while durable disease control is pursued across decades-long survivorship.

This work delivers multidisciplinary consensus recommendations to standardize care in IDH-mutant grade 2 gliomas, integrating advances in molecular diagnostics, imaging, and therapeutics. It also identifies key knowledge gaps and clinical uncertainties, underscoring the critical need for ongoing research and expert collaboration to continually refine personalized management approaches and improve patient outcomes.

P1, N=18, Recruiting, Memorial Sloan Kettering Cancer Center | N=36 --> 18

P2, N=35, Recruiting, City of Hope Medical Center | Suspended --> Recruiting

P=N/A, N=10, Not yet recruiting, Huashan Hospital

P1, N=60, Active, not recruiting, Institut de Recherches Internationales Servier | Recruiting --> Active, not recruiting

At the last follow-up, 3 years after vorasidenib discontinuation, the disease remained stable in 1 patient, while the other one had recurred. Vorasidenib does not appear to select an IDH-wildtype clone that would potentially reduce the tumor's sensitivity to standard therapies typically used in IDH-mutated glioma.

P2, N=35, Suspended, City of Hope Medical Center | Recruiting --> Suspended

P1, N=36, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P2, N=93, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P1/2, N=130, Active, not recruiting, Celgene | Trial completion date: Sep 2025 --> Sep 2026