IDH2 mutation (R140 and R172)

aka IDH2 R140Q, IDH2 R172K, IDH2 mutation, IDH2-mutant, mIDH2

IDH2 mutations at codons 140 and 172 do the same job as IDH1 R132, producing 2-HG. Enasidenib is approved for relapsed AML with them, and vorasidenib for grade 2 gliomas with either IDH gene mutated.

R140Q is the commonest IDH2 mutation in AML; R172K predominates in glioma and angioimmunoblastic T-cell lymphoma. Enasidenib (Idhifa, 2017) is labelled for relapsed or refractory AML with an IDH2 mutation as detected by an FDA-approved test, the Abbott RealTime IDH2 assay listing R140Q, R140L, R140G, R140W, R172K, R172M, R172G, R172S and R172W; vorasidenib covers IDH2 R172 mutations in grade 2 glioma with the Oncomine Dx Target Test. IDH2-mutant AML has a lower rate of differentiation syndrome recognition problems only because the drug is older; the risk is the same class effect.

Part ofIDH1 / IDH2· IDH1, IDH2Other readoutsIDH1 R132 mutation All readouts

IDH1 / IDH2: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.

Sequencing 2 approval thresholds

What it means for a patient

An IDH2 mutation in acute myeloid leukaemia that has come back opens enasidenib tablets; in a grade 2 glioma after surgery it opens vorasidenib. Both drugs can cause differentiation syndrome in leukaemia, a reaction your team will watch for in the first weeks.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

An IDH2 codon 140 or 172 substitution (R140Q, R140L, R140G, R140W, R172K, R172M, R172G, R172S, R172W) by PCR or sequencing.

“R140Q, R140L, R140G, R140W, R172K, R172M, R172G, R172S, and R172W”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
IDH2 mutation	Enasidenib	IDH1- and IDH2-mutated acute myeloid leukaemia	FDA	label
Susceptible IDH1 or IDH2 mutation, grade 2 glioma	Vorasidenib	Oligodendroglioma, IDH-mutant and 1p/19q-codeleted	FDA	label

Drugs whose label names it

Enasidenib Vorasidenib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
Abbott RealTime IDH2	Abbott Molecular	Acute Myeloid Leukemia - Peripheral Blood or Bone Marrow	Enasidenib	P170005 (08/01/2017)

Tests that measure it

Oncomine Dx Target Test Abbott RealTime IDH2 Tempus xT and xT CDx FoundationOne Heme NeoGenomics NeoTYPE profiles

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.