KIT D816V mutación de punto de activación (exón 17, bucle de activa...

Vista determinista de la entidad fuente YAML. La autoridad clínica sigue con los ID de fuente citados y estado de firma del revisor.

ID	`RF-ADVSM-KIT-D816V`
Tipo	Señal de alerta
Situación	reviewed 2026-05-08 \| pending_clinical_signoff
Enfermedades	`DIS-MASTOCYTOSIS`
Fuentes	`SRC-EXPLORER` `SRC-NCCN-SM-2025` `SRC-PATHFINDER`

Origen de la bandera roja

Definición	KIT D816V activating point mutation (exon 17, activation loop) in advanced systemic mastocytosis (ASM, SM-AHN, mast cell leukemia per WHO 2022). KIT D816V is present in >90% of systemic mastocytosis cases and is the defining molecular driver. D816V confers resistance to imatinib (steric clash at the drug-binding site; imatinib is INACTIVE against D816V). However, avapritinib — a type I KIT inhibitor designed to bind the active (DFG-in) conformation — potently inhibits D816V kinase activity. Fires to route ALGO-ADVSM-1L step 1 toward avapritinib (IND-ADVSM-1L- AVAPRITINIB) as the preferred 1L option, contingent on adequate platelet count (≥50 ×10⁹/L; enforced as a separate condition in the step all_of gate). If platelets <50 ×10⁹/L or avapritinib is inaccessible despite D816V positivity, midostaurin (IND-ADVSM-1L-MIDOSTAURIN) remains appropriate. Clinical evidence: - PATHFINDER (avapriti...
Dirección clínica	intensificar
Categoría	high-risk-biology
Algoritmo de cambios	ALGO-ADVSM-1L

Lógica de activación

{
  "any_of": [
    {
      "finding": "BIO-KIT",
      "value": "D816V"
    },
    {
      "finding": "kit_mutation",
      "value": "D816V"
    },
    {
      "finding": "kit_d816v_status",
      "value": "positive"
    },
    {
      "finding": "kit_d816v_status",
      "value": "detected"
    },
    {
      "finding": "kit_d816v_status",
      "value": "mutant"
    },
    {
      "finding": "kit_exon17_mutation",
      "value": "D816V"
    }
  ],
  "type": "biomarker_status"
}

Notas

W5c RF authoring. Converts free-text `{condition: "KIT D816V positive"}` in ALGO-ADVSM-1L step 1 (all_of composite) into a formal RF entity. The step uses all_of: [biomarker gate, platelet-count gate] — this RF formalizes the biomarker half; the platelet-count condition (≥50 ×10⁹/L) remains a free-text MDT-evaluated condition in the algo (no platelet- threshold RF entity in current KB design). Clinical rationale: Avapritinib has superior molecular response depth vs midostaurin (KIT D816V VAF reduction in BM; Gotlib JCO 2023 PATHFINDER cohort). Platelet threshold of ≥50 ×10⁹/L is from avapritinib prescribing information due to risk of intracranial hemorrhage in severe thrombocytopenia. Midostaurin does NOT have this platelet restriction — rationale for algo step 2 fallback. Important KIT D816V disambiguation: This RF is for SYSTEMIC MASTOCYTOSIS (DIS-MASTOCYTOSIS). KIT mutations in GIST are exon 11/9/13/17, not the same D816V codon; imatinib is active against GIST KIT exon 11/9 but NOT D816V. This RF must NOT be triggered in GIST patients. The `relevant_diseases: [DIS-MASTOCYTOSIS]` constraint ensures disease-scoped routing. BMA-KIT-D816V-MASTOCYTOSIS (ESCAT IA): confirms evidence...

Utilizado por

Algoritmos

ALGO-ADVSM-1L - ALGO-ADVSM-1L