Ivosidenib or venetoclax combined with hypomethylating agents in IDH1-mutated acute myeloid leukemia: a real-world study

Approximately 10% of patients with newly diagnosed acute myeloid leukemia (ND-AML) harbor the isocitrate dehydrogenase 1 gene mutation (m<i>IDH1</i>). In this real-world study evaluating ivosidenib (IVO) + hypomethylating agents (HMAs; n = 181) vs venetoclax (VEN) + HMAs (n = 99) in patients with m<i>IDH1</i> ND-AML, those treated with IVO+HMA had higher rates of complete remission (CR; 42.5% vs 26.3%; <i>P</i> = .007), higher rates of composite CR + CR with incomplete platelet count recovery (63.0% vs 48.5%; <i>P</i> = .019), shorter median time to best response (3.3 vs 4.1 months; <i>P</i> = .006), and improved 6-month event-free survival (55.8% vs 38.4%; <i>P</i> = .006). Most patients treated with VEN received well under 28 days of VEN per cycle, likely due to anticipation of toxicity; outcomes with this short-schedule VEN were proportionately worse with fewer days of exposure per cycle. The between-group rate of grade ≥3 adverse events was similar within 30 days of treatment initiation, except for higher rates of febrile neutropenia for VEN+HMA vs IVO+HMA (8.1% vs 1.7%; <i>P</i> = .008). These findings support results from the phase 3 AGILE trial demonstrating IVO+HMA's efficacy and favorable toxicity profile in patients with m<i>IDH1</i> ND-AML. IVO + azacitidine should be considered as the preferred standard of care treatment regimen in this patient subgroup.