IMT progression on first-line crizotinib (acquired ALK kinase-domain resistance mutation...

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

ID	`RF-IMT-TRANSFORMATION-PROGRESSION`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-IMT`
Sources	`SRC-NCCN-SARCOMA` `SRC-ONCOKB`

Red Flag Origin

Definition	IMT progression on first-line crizotinib (acquired ALK kinase-domain resistance mutation L1196M / G1202R / I1171N), dedifferentiation into high-grade sarcoma (epithelioid inflammatory myofibroblastic sarcoma variant), new metastatic disease, or rapid local progression — triggers switch to lorlatinib / alectinib (next-gen ALK), repotrectinib (ROS1), or salvage cytotoxic chemotherapy.
Clinical direction	hold
Category	transformation-progression

Trigger Logic

{
  "any_of": [
    {
      "finding": "BIO-ALK-G1202R",
      "value": "positive"
    },
    {
      "finding": "BIO-ALK-L1196M",
      "value": "positive"
    },
    {
      "finding": "alk_resistance_mutation",
      "value": true
    },
    {
      "finding": "epithelioid_inflammatory_sarcoma_dedifferentiation",
      "value": true
    },
    {
      "finding": "new_metastatic_disease",
      "value": true
    },
    {
      "finding": "rapid_progression_on_tki",
      "value": true
    }
  ],
  "type": "composite_clinical"
}

Notes

Most IMT is intermediate-behavior; epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive variant with exclusively ALK-fusion (typically RANBP2-ALK) that behaves like high-grade sarcoma — distinct prognosis, often metastatic at diagnosis, requires aggressive systemic therapy + surgery. Acquired ALK resistance mutations (L1196M gatekeeper, G1202R solvent-front, I1171N) drive crizotinib failure within 12-18 mo — switch to lorlatinib (covers most resistance variants) or alectinib (covers L1196M, less G1202R). ROS1+ progression: repotrectinib (TRIDENT-1). Re-biopsy at progression strongly recommended for resistance genotyping.

Used By

No reverse references found in the YAML corpus.