KIT D816V in fortgeschrittener systemischer Mastozytose (AdvSM — aggressives SM, SM-AHN, Mastzellleu...
Deterministische Ansicht der Quelle YAML Entität. Klinische Autorität bleibt mit den zitierten Quell-IDs und Rezensenten Sign-off Zustand.
| ID | BMA-KIT-D816V-MASTOCYTOSIS |
|---|---|
| Art | Therapeutische Relevanz |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Erkrankungen | DIS-MASTOCYTOSIS |
| Quellen | SRC-CIVIC SRC-NCCN-MELANOMA-2025 |
Fakten zur Handlungsfähigkeit
| Biomarker | BIO-KIT |
|---|---|
| Variante | D816V (Aktivierungsschleife, Exon 17 — > 90% der fortgeschrittenen systemischen Mastozytose) |
| Erkrankung | DIS-MASTOCYTOSIS |
| ESCAT-Stufe | IA |
| Empfohlene Kombinationen | avapritinib Monotherapie (bevorzugt 1L AdvSM pro PATHFINDER), Midostaurin Monotherapie, (alternativ; breitere Registrierung) |
| Kontraindizierte Monotherapie | imatinib (D816V resistant — only KIT-WT or non-D816V AdvSM benefits) |
| Zusammenfassung der Beweise | KIT D816V in advanced systemic mastocytosis (AdvSM — aggressive SM, SM-AHN, mast cell leukemia): midostaurin (EXPLORER / D2201 phase 2, Gotlib NEJM 2016 — ORR 60%) and avapritinib (PATHFINDER / EXPLORER, Gotlib JCO 2023 — ORR 75%, deeper molecular response) are FDA- approved. Avapritinib selectively targets the D816V conformation with high potency. Imatinib is INACTIVE against D816V — distinct from imatinib-sensitive juxtamembrane mutations. |
Anmerkungen
ESCAT IA. OncoKB Level 1. Source-gap: SRC-NCCN-SM-2025 / SRC-EXPLORER / SRC-PATHFINDER not yet ingested. AdvSM diagnosis requires WHO- defined C-findings (cytopenias, hepatomegaly + dysfunction, organ damage). Indolent SM is generally NOT treated with KIT-TKI; symptomatic treatment only.
Verwendet von
Warnhinweis
RF-ADVSM-KIT-D816V- KIT D816V Aktivierungspunktmutation (Exon 17, Aktivierungsschleife) im fortgeschrittenen systemischen Masto...