IDH2 R140Q or R172K activating mutation in AML — ~8-12% prevalence. Enasidenib (IDHIFA /...

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

ID	`RF-AML-IDH2-MUT-ACTIONABLE`
Type	Red flag
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	`DIS-AML`
Sources	`SRC-ELN-AML-2022` `SRC-ESMO-AML-2020` `SRC-NCCN-AML-2025`

Red Flag Origin

Definition	IDH2 R140Q or R172K activating mutation in AML — ~8-12% prevalence. Enasidenib (IDHIFA / IDHENTIFY — phase-3 R/R AML; monotherapy ORR 38%, CR 19%) is FDA-approved for R/R-AML-IDH2; also active 1L combination with azacitidine in unfit (AG221-AML-005 — ORR 71%).
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-AML-1L, ALGO-AML-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "idh2_r140q",
      "value": true
    },
    {
      "finding": "idh2_r172k",
      "value": true
    },
    {
      "finding": "idh2_mutation",
      "value": true
    },
    {
      "finding": "idh2_status",
      "value": "mutated"
    },
    {
      "finding": "idh_mutation",
      "value": "IDH2"
    }
  ],
  "type": "biomarker"
}

Notes

Detection: NGS panel (no IDH2-specific IHC widely deployed). Differentiation syndrome on enasidenib (~14%) — same monitoring + dexamethasone protocol as ivosidenib. Hyperbilirubinemia on enasidenib (~80% any grade; UGT1A1 inhibition — usually asymptomatic, no dose adjustment unless symptomatic). IDHENTIFY R/R AML did not show OS benefit vs conventional care over all comers but enriched in IDH2-mut who had not received prior hypomethylating agent. Combination with venetoclax + azacitidine under study.

Used By

Algorithms

ALGO-AML-1L - ALGO-AML-1L
ALGO-AML-2L - ALGO-AML-2L

Biomarker

BIO-IDH2-R140Q - IDH2 R140Q mutation (AML)
BIO-IDH2-R172K - IDH2 R172K mutation (AML)

Indications

IND-AML-2L-IDH2-ENASIDENIB - IND-AML-2L-IDH2-ENASIDENIB