IDH1/IDH2 mutation is the defining molecular feature of WHO grade 2 (and 3) diffuse gliom...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-IDH-MUTATION-GLIOMA-LOW-GRADE |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-03 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-GLIOMA-LOW-GRADE |
| Sources | SRC-EANO-LGG-2024 SRC-NCCN-CNS-2025 |
Actionability Facts
| Biomarker | BIO-IDH-MUTATION |
|---|---|
| Variant | IDH1 or IDH2 mutation (IDH1 R132H most common >90%; IDH1 R132C/G/S/L; IDH2 R140Q/R172K — WHO CNS grade 2 astrocytoma or oligodendroglioma context) |
| Disease | DIS-GLIOMA-LOW-GRADE |
| ESCAT tier | IA |
| Recommended combinations | vorasidenib 40 mg PO once daily monotherapy (post-surgical 1L; INDIGO regimen) |
| Contraindicated monotherapy | ivosidenib monotherapy (IDH1 CNS penetration insufficient for brain; ivosidenib is approved for AML and cholangiocarcinoma, not glioma) |
| Evidence summary | IDH1/IDH2 mutation is the defining molecular feature of WHO grade 2 (and 3) diffuse gliomas — astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant and 1p/19q codeleted. Vorasidenib (dual IDH1/IDH2 inhibitor) is FDA-approved (Aug 2024) for IDH1- or IDH2-mutated grade 2 glioma in adults following prior surgery. INDIGO trial (Mellinghoff et al. NEJM 2023 — phase III, 331 pts): vorasidenib 40 mg/day vs placebo; mPFS 27.7 vs 11.1 mo (HR 0.39, p<0.001); 61% reduction in risk of progression or death; time to next intervention also significantly improved. The approval defines a new 1L systemic standard after surgery for IDH-mutant grade 2 glioma. EANO 2024 guidelines incorporate vorasidenib as preferred systemic option at progression or post-biopsy-only grade 2 IDH-mutant glioma. IDH1 R132H accounts for >90% of IDH-mutant LGG; IDH2 mutations ~3-5%; rare non-R132H IDH1 mutations ~5%. |
Notes
ESCAT IA. INDIGO trial is the first phase III RCT to demonstrate PFS benefit with a targeted agent in low-grade glioma. IDH mutation testing by next-generation sequencing or immunohistochemistry (IDH1 R132H antibody — covers >90%) is now mandatory in all WHO grade 2-3 glioma per WHO CNS 2021 classification. Vorasidenib has better CNS penetration than ivosidenib (specifically developed for brain tumor context). Strong safety profile: hepatotoxicity monitoring (LFTs) required — grade 3+ ALT elevation ~10%. Do not confuse with GBM (IDH-wildtype grade 4) where vorasidenib has no approval.
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