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Adding the IDH1 inhibitor ivosidenib to azacitidine tripled median survival, from 7.9 to 24 months, in older patients with IDH1-mutated AML.
AGILE randomised 146 patients with newly diagnosed IDH1-mutated AML who were ineligible for intensive induction to ivosidenib plus azacitidine or placebo plus azacitidine. The primary endpoint was event-free survival. EFS favoured ivosidenib (hazard ratio 0.33), complete remission was 47% versus 15%, and median overall survival was 24.0 versus 7.9 months (hazard ratio 0.44). Differentiation syndrome occurred in 14% of ivosidenib patients; febrile neutropenia and infections were less frequent than with azacitidine alone, partly because of faster count recovery. The result established a mutation-directed doublet for this subgroup.
AGILE showed that for the roughly 6-10% of AML patients with an IDH1 mutation, a targeted doublet produces survival in the range of two years, an outcome previously unimaginable in unfit patients. Ivosidenib-azacitidine is approved and is one option alongside venetoclax-azacitidine for these patients. Which regimen, or triplet, is best for IDH1-mutated disease has not been settled by a randomised trial.
Shares Servier, Ivosidenib, Acute myeloid leukaemia in older or unfit patients, Azacitidine.
Shares Courtney D. DiNardo, VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy, IDH1- and IDH2-mutated acute myeloid leukaemia, Acute myeloid leukaemia in older or unfit patients.
Shares VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy, Acute myeloid leukaemia in older or unfit patients, Azacitidine, Venetoclax.
Shares IDH1- and IDH2-mutated acute myeloid leukaemia, Ivosidenib, New England Journal of Medicine.
Shares Acute myeloid leukaemia in older or unfit patients, Azacitidine, Venetoclax, Acute myeloid leukaemia.
Shares VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy, Acute myeloid leukaemia in older or unfit patients, Azacitidine, Venetoclax.
Shares Acute myeloid leukaemia in older or unfit patients, Azacitidine, New England Journal of Medicine, Acute myeloid leukaemia.
Shares Acute myeloid leukaemia in older or unfit patients, Azacitidine, Venetoclax, Acute myeloid leukaemia.