https://orcid.org/0000-0001-8506-0624
KEY POINTS
In this real-world study of patients with mIDH1 ND-AML, IVO+HMA improved CR, time to response, EFS, and other outcomes compared with VEN+HMA.
With enhanced efficacy and a favorable safety profile, IVO+HMA warrants consideration as the preferred treatment in ICi mIDH1 ND-AML.
Abstract
Approximately 10% of patients with newly diagnosed acute myeloid leukemia (ND-AML) harbor the isocitrate dehydrogenase 1 gene mutation (mIDH1). In this real-world study evaluating ivosidenib + hypomethylating agents (IVO+HMA, N = 181) vs venetoclax (VEN)+HMA (N = 99) in patients with mIDH1 ND-AML, those treated with IVO+HMA had higher rates of complete remission (CR; 42.5% vs 26.3%, P = .007); higher rates of composite CR+CR with incomplete platelet count recovery (CRi/p; 63.0% vs 48.5%, P = .019); shorter median time to best response (3.3 vs 4.1 months, P = .006); and improved 6-month event-free survival (EFS; 55.8% vs 38.4%, P = .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 adverse events grade ≥3 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%, P = .008). These findings support the results from the phase 3 AGILE trial demonstrating IVO+HMA’s efficacy and favorable toxicity profile in mIDH1 ND-AML patients. IVO+azacitidine should be considered as the preferred standard of care treatment regimen in this patient subgroup.
Author notes
At the time the study was conducted
DATA SHARING STATEMENT
Study-level results will be made available upon reasonable request from a qualified medical or scientific professional for the specific purpose laid out in that request. The data for this request will be available after a data access agreement has been signed. Please send your data sharing request via email to the corresponding author.
EXPLANATION OF NOVELTY
To our knowledge, this is the first study directly comparing IVO+HMA vs VEN+HMA in patients with mIDH1 ND-AML. This study reports CR outcomes for VEN across different schedules per cycle, finding that short schedules were most commonly used yet led to worse rate, speed, and duration of CR without less toxicity. These results suggest that IVO+HMA should become the preferred standard of care treatment regimen in patients with mIDH1 ND-AML.
