KIT D816V in advanced systemic mastocytosis (AdvSM — aggressive SM, SM-AHN, mast cell leu...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-KIT-D816V-MASTOCYTOSIS |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-MASTOCYTOSIS |
| Sources | SRC-CIVIC SRC-NCCN-MELANOMA-2025 |
Actionability Facts
| Biomarker | BIO-KIT |
|---|---|
| Variant | D816V (activation loop, exon 17 — >90% of advanced systemic mastocytosis) |
| Disease | DIS-MASTOCYTOSIS |
| ESCAT tier | IA |
| Recommended combinations | avapritinib monotherapy (preferred 1L AdvSM per PATHFINDER), midostaurin monotherapy (alternative; broader registration) |
| Contraindicated monotherapy | imatinib (D816V resistant — only KIT-WT or non-D816V AdvSM benefits) |
| Evidence summary | 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. |
Notes
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.
Used By
Red flag
RF-ADVSM-KIT-D816V- KIT D816V activating point mutation (exon 17, activation loop) in advanced systemic masto...