IDH1 mutations can play a critical role in the development of AML1-4
IDH1 mutations block normal differentiation of myeloblasts3,4 |
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![]() ![]() Normal differentiation of myeloblasts is blocked ![]() ![]() Unchecked proliferation of undifferentiated myeloblasts occurs |
IDH1 mutations are driver mutations and occur in 6% to 10% of patients with AML2
IDH1 mutations have been associated with a negative prognosis in AML5
Test for IDH1 mutations at diagnosis so you can offer targeted therapy to appropriate patients6
- Patients without IDH1 mutations at diagnosis should be retested at relapse because a mutation in IDH1 may emerge during treatment and at relapse7
- 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 TIBSOVO7
- Both the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) and ASH‑CAP Guidelines recommend testing for IDH1 mutations in patients with AML6,8
- NCCN Guidelines® recommend ivosidenib (TIBSOVO) + azacitidine as a category 1 preferred treatment option for newly diagnosed patients ≥60 years of age with mIDH1 who are not candidates for intensive remission induction therapy8
- NCCN Guidelines recommend ivosidenib (TIBSOVO) monotherapy for IC-ineligible newly diagnosed and R/R AML patients with an IDH1 mutation8
TIBSOVO (ivosidenib tablets) targets the mutant IDH1 enzyme to restore myeloid differentiation3,7
TIBSOVO restores differentiation of myeloblasts3,7 |
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![]() ![]() The block on myeloblast differentiation is released ![]() ![]() Differentiation of myeloblasts into mature blood cells occurs |
- 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 cells7
- Ivosidenib was shown to inhibit selected IDH1 R132 mutants at much lower concentrations than wild-type IDH1 in vitro7
- 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
methods7
- Susceptible IDH1 mutations are R132C, R132G, R132H, R132L, and R132S7