KIT activating mutation (exon 11 / 13) in mucosal or acral melanoma subtype — ~15-20% pre...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-MELANOMA-KIT-MUT-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-MELANOMA`
Sources	`SRC-CARVAJAL-KIT-MELANOMA-2013` `SRC-ESMO-MELANOMA-2024` `SRC-NCCN-MELANOMA-2025`

Red Flag Origin

Definition	KIT activating mutation (exon 11 / 13) in mucosal or acral melanoma subtype — ~15-20% prevalence in those subtypes (rare in cutaneous). Imatinib (Carvajal 2013 — ORR 23% in KIT-mut mucosal/acral) and nilotinib are off-label active; integrate with standard IO if eligible.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-MELANOMA-METASTATIC-1L, ALGO-MELANOMA-METASTATIC-2L

Trigger Logic

{
  "all_of": [
    {
      "any_of": [
        {
          "finding": "kit_mutation",
          "value": true
        },
        {
          "finding": "kit_status",
          "value": "mutated"
        },
        {
          "finding": "kit_exon11",
          "value": "positive"
        },
        {
          "finding": "kit_exon13",
          "value": "positive"
        }
      ]
    },
    {
      "any_of": [
        {
          "finding": "melanoma_subtype",
          "value": "mucosal"
        },
        {
          "finding": "melanoma_subtype",
          "value": "acral"
        },
        {
          "finding": "primary_site",
          "value": "mucosal"
        },
        {
          "finding": "primary_site",
          "value": "acral"
        }
      ]
    }
  ],
  "type": "composite_score"
}

Notes

KIT mutations very rare (<3%) in cutaneous melanoma — testing reserved for mucosal / acral / chronic-sun-damaged subtypes per guidelines. Exon 17 D816V resistance to imatinib (avapritinib active for D816V — limited mucosal-melanoma data). Mucosal melanoma generally has lower IO response than cutaneous; KIT-TKI + IO sequencing under study. Mucosal-melanoma 1L typically ipi-nivo (KEYNOTE-029, CheckMate-067 subset); KIT-TKI is second-line consideration in KIT-mut subset.

Used By

Algorithms

ALGO-MELANOMA-METASTATIC-1L - ALGO-MELANOMA-METASTATIC-1L
ALGO-MELANOMA-METASTATIC-2L - ALGO-MELANOMA-METASTATIC-2L