IDH1 mutations can play a critical role in the development of AML1-4
IDH1 mutations block normal differentiation of myeloblasts1-3
IDH1 mutations are driver mutations that occur in up to 14% of patients with AML2,4
- mIDH1 contributes to oncogenesis by catalyzing the production of 2-HG, which leads to disruption of cellular metabolism and epigenetic regulation5
- Several studies have suggested that mIDH1 AML is associated with a poor prognosis5,6
2-HG, D-2-hydroxyglutarate; AML, acute myeloid leukemia; IDH1, isocitrate dehydrogenase‑1.
Test for IDH1 mutations at diagnosis and relapse so you can offer targeted therapy to appropriate patients7,8
- Both the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) and ASH‑CAP Guidelines recommend testing for IDH1 mutations in patients with AML7,8
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"To appropriately stratify available intensive therapy options, expedite test results of molecular and cytogenetic analyses for immediately actionable mutations or chromosomal abnormalities (eg, core binding factor [CBF], FLT3 [ITD and TKD], NPM1, IDH1, IDH2)”
- National Comprehensive Cancer Network® (NCCN®)8 - Patients without IDH1 mutations at diagnosis should be retested at relapse because a mutation in IDH1 may emerge during treatment and at relapse9
- In the pivotal trials, IDH1 mutations were identified by a local or central diagnostic test and confirmed retrospectively using the Abbott RealTime IDH1 assay, which is the FDA-approved test for selection of patients with AML for treatment with TIBSOVO9
- NCCN Guidelines® recommends ivosidenib (TIBSOVO) + azacitidine as a category 1 preferred treatment option for newly diagnosed patients with mIDH1 who are not candidates for intensive remission induction therapy8
- NCCN Guidelines recommends ivosidenib (TIBSOVO) monotherapy for IC-ineligible, newly diagnosed and R/R AML patients with an IDH1 mutation8
AML, acute myeloid leukemia; ASH, American Society of Hematology; CAP, College of American Pathologists; IC, induction chemotherapy; IDH1, isocitrate dehydrogenase‑1; R/R, relapsed/refractory.
TIBSOVO (ivosidenib tablets) targets the mutant IDH1 enzyme to restore myeloid differentiation1,9
TIBSOVO restores differentiation of myeloblasts1,9
- In blood samples from patients with AML with mutated IDH1, ivosidenib decreased 2-HG levels ex vivo, reduced blast counts, and increased percentages of mature myeloid cells9
- Ivosidenib was shown to inhibit selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro9
- Susceptible IDH1 mutations are defined as those leading to increased levels of 2-HG in the leukemia cells and where efficacy is predicted by (1) clinically meaningful remissions with the recommended dose of ivosidenib and/or (2) inhibition of mutant IDH1 enzymatic activity at concentrations of ivosidenib sustainable at the recommended dosage according to validated methods9
- Susceptible IDH1 mutations are R132C, R132G, R132H, R132L, and R132S9
2-HG, D-2-hydroxyglutarate; AML, acute myeloid leukemia; IDH1, isocitrate dehydrogenase‑1.