IDH Triplet (AZA/DEC + Venetoclax + Ivo/Enas) Delivers 92% CRc and 69% 2-Year OS in Intensive chemo-Ineligible AML

A single-center series (NCT03471260/NCT04774393) treated 60 newly diagnosed, intensive-chemo–ineligible IDH-mutated AML patients with a hypomethylating agent (HMA) azacitidine or oral decitabine plus venetoclax and an IDH inhibitor (ivosidenib for IDH1, enasidenib for IDH2). ); 20% of AML cases express an IDH1 or IDH2 mutation (8% and 12% of cases, respectively, according to a 2021 study%20genes%2C%20IDH1%20or%20IDH2.). Early mortality was 2%. Composite complete remission reached 92% (CR/CRi 55/60; ORR 95%), and with 27 mo median follow-up median OS is still unreached; 2-year OS stands at 69% with a 24% relapse rate. Outcomes dipped for treated-secondary AML (CRc 71%, 2-yr OS 34%), while de-novo cases saw 84% OS. Toxicities mirrored HMA-VEN or HMA-IDH doublets, and 32% proceeded to transplant. For context, the VIALE-A azacitidine-venetoclax doublet posts CRc 66% and mOS 15–25 mo, while the AGILE azacitidine-ivosidenib doublet shows CR 47% and mOS 24 mo—making this oral triplet the current efficacy high-water mark for frail IDH-mut AML.