MAPK-Wegaktivierung ist das Markenzeichen von pädiatrischen Low-Grade-Gliom (pLGG) und Occ...
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| ID | BMA-MAP2K1-LGG |
|---|---|
| Art | Therapeutische Relevanz |
| Status | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Erkrankungen | DIS-GLIOMA-LOW-GRADE |
| Quellen | SRC-EANO-LGG-2024 SRC-NCCN-CNS-2025 |
Fakten zur Handlungsfähigkeit
| Biomarker | BIO-MAP2K1 |
|---|---|
| Variante | MAP2K1 Aktivierungsmutation — niedriggradiges Gliom (LGG); BRAF-Fusions-negativ, IDH-wildtyp oder IDH -mutant; MAPK-Weg alternative Aktivierung |
| Erkrankung | DIS-GLIOMA-LOW-GRADE |
| ESCAT-Stufe | IIA |
| Empfohlene Kombinationen | trametinib 0.025 mg/kg PO QD (pediatric dosing; adult 2 mg/day) — MAP2K1-mutant LGG investigational (TRAM-01 regimen), tovorafenib 420 mg/m² PO QW — BRAF-altered or MAPK-pathway-altered pLGG (FIREFLY-1 eligible), clinical trial enrollment preferred for MAP2K1-mutant LGG (adult or pediatric) |
| Zusammenfassung der Beweise | MAPK pathway activation is the hallmark of pediatric-type low-grade glioma (pLGG) and occurs in ~90% via BRAF-KIAA1549 fusion (~70%), BRAF V600E (~15%), or alternative MAPK alterations including MAP2K1 mutations (~5–10% of BRAF-fusion-negative pLGG). The FIREFLY-1 phase II trial (Kilburn et al., JCO 2024) demonstrated tovorafenib (type II RAF inhibitor) activity in pLGG with MAPK pathway alterations including MAP2K1 mutations: ORR 67% overall; MAP2K1 cohort showed responses. Trametinib (MEK1/2 inhibitor) has demonstrated activity in MAPK-pathway-altered pLGG in the TRAM-01 and FIREFLY-2 trials. In adult LGG, MAP2K1 mutations occur in ~5% (predominantly IDH-wildtype histiocytic NEC); data more limited. For adult IDH-mutant LGG, vorasidenib (IDH1/2 inhibitor) is now standard (INDIGO trial; FDA 2024) — see BMA-IDH-MUTATION-GLIOMA-LOW-GRADE. MAP2K1 mutations in adult LGG without IDH: MEK inhibitors investigational. NCCN CNS 2025: trametinib / tovorafenib Category 2A for MAPK-altered pLGG. |
Anmerkungen
ESCAT IIA: MAP2K1 is an actionable MAPK pathway alteration in LGG; MEK inhibitors (trametinib) and RAF inhibitors (tovorafenib) active. BRAF fusion testing (FISH/RNA-seq) should be performed first in pLGG — BRAF-KIAA1549 fusion is the dominant driver and is most robustly treated with RAF inhibitors. MAP2K1 mutation may be identified when BRAF fusion and BRAF V600E are absent. IDH1/2 mutation status is critical for adult LGG: IDH-mutant → vorasidenib; IDH-wildtype + MAP2K1 → MEK inhibitors investigational. Comprehensive molecular testing recommended: IDH1/2, BRAF (fusion + V600E), MAP2K1, CDKN2A/B, 1p/19q codeletion (molecular oligodendroglioma), TERT promoter.
Verwendet von
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