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EHA 2026 | IDH1-targeted therapy continues to reshape AML treatment
Agnieszka Wierzbowska, MD, PhD, Medical University of Lodz, Lodz, Poland, discusses the evolving treatment landscape for IDH1-mutated acute myeloid leukemia (AML). She reviews the impact of ivosidenib-based therapy, highlights promising early results from triplet combinations with venetoclax and azacitidine, and explains how ongoing Phase III studies could further redefine the standard of care for patients unfit for intensive chemotherapy. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
IDH1 mutation is a relatively rare genetic event in acute myeloid leukemia. It’s present in about 6 to 10% of patients. The presence of IDH1 mutation is associated with the hypermethylation status in AML patients. So the implementation of IDH1-targeted therapies, IDH1 inhibitors, changed the treatment paradigm of elderly AML patients treated with less intensive chemotherapies. The results of the Agile study clearly showed that the addition of IDH1-inhibitor ivosidenib to conventional hypomethylating agents, in this case azacitidine, significantly improved overall survival with the median overall survival 24 months versus at least eight months with azacitidine alone...
IDH1 mutation is a relatively rare genetic event in acute myeloid leukemia. It’s present in about 6 to 10% of patients. The presence of IDH1 mutation is associated with the hypermethylation status in AML patients. So the implementation of IDH1-targeted therapies, IDH1 inhibitors, changed the treatment paradigm of elderly AML patients treated with less intensive chemotherapies. The results of the Agile study clearly showed that the addition of IDH1-inhibitor ivosidenib to conventional hypomethylating agents, in this case azacitidine, significantly improved overall survival with the median overall survival 24 months versus at least eight months with azacitidine alone. Moreover, the combination with azacitidine and ivosidenib was associated with significantly higher composite complete remission rate 53 versus 17 percent only with the placebo arm so the extended period of the follow-up also showed increased median overall survival in ivosidenib in combination with azacitidine to 29.4 months. So right now the combination ivosidenib with azacitidine is a new standard of care for elderly AML patients. However, this field is developing rapidly and novel targeted therapies are combined to the conventional azacitidine-venetoclax backbone, including IDH1 inhibitors. And at this Congress, the fantastic results of the Phase I, Phase II study were presented showing that the combined treatment, ivosidenib-venetoclax and azacitidine, is well correlated with low early mortality rate and also particularly effective with the composite complete remission rate exceeding 95% and the long-term overall survival observed also in about 90% of patients. So I think that, of course, the randomized phase 3 studies are required to confirm these fantastic early phase results. And currently, this study was initiated. The EVOLVE-1 study plans to compare the triplet regimen, ivosidenib-venetoclax-azacitidine with a doublet, ivosidenib-azacitidine, in newly diagnosed AML patients, IDH1 mutated who are unfit for intensive chemotherapy.
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