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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
IDH-mutated acute myeloid leukaemia has a faulty metabolic enzyme that floods cells with a chemical that blocks maturation. Pills that shut the enzyme off, ivosidenib for IDH1 and enasidenib or olutasidenib for IDH2 and IDH1, let the leukaemia cells mature, and ivosidenib with azacitidine tripled survival in older patients.
Mutant isocitrate dehydrogenase 1 or 2 makes the oncometabolite 2-hydroxyglutarate, which jams the DNA-demethylating enzymes that blood cells need to differentiate. IDH2 mutations (R140, R172) occur in roughly one in eight adult AML and IDH1 (R132) in about one in twelve. They co-occur with NPM1 and DNMT3A mutations and are enriched in older patients. Blocking the mutant enzyme does not kill the blast directly; it restores differentiation over weeks, and the price is differentiation syndrome in around a fifth of patients.
Enasidenib, approved in 2017 for relapsed or refractory IDH2-mutated AML on a phase 1/2 study, was the first IDH inhibitor; its phase 3 IDHENTIFY trial against conventional care in older relapsed patients did not lengthen survival. Ivosidenib followed in 2018 for relapsed IDH1-mutated disease and, after AGILE (2022), for newly diagnosed patients unfit for intensive chemotherapy: ivosidenib plus azacitidine gave a median overall survival of 24.0 months against 7.9 months with azacitidine alone (hazard ratio 0.44). Olutasidenib, a second IDH1 inhibitor, was approved for relapsed disease in 2022.
| Setting | Approach | Guideline |
|---|---|---|
| Newly diagnosed IDH1-mutated, unfit for intensive chemotherapy | Ivosidenib plus azacitidine (AGILE) or venetoclax plus azacitidine; triplets in trials. | not mapped |
| Newly diagnosed, fit for intensive chemotherapy | 7+3 induction with consolidation and transplant by ELN risk; IDH inhibitors added in trials. | not mapped |
| Relapsed or refractory | Ivosidenib or olutasidenib for IDH1, enasidenib for IDH2; venetoclax-based combinations; transplant in responders. | not mapped |