In a single-center study reported in the Journal of Clinical Oncology, DiNardo et al investigated whether frontline triplet regimens consisting of a hypomethylating agent, venetoclax, and an isocitrate dehydrogenase inhibitor were active in intensive chemotherapy-ineligible patients with IDH-mutant acute myeloid leukemia (AML).
Study Details
Sixty patients were enrolled at the study, conducted at The University of Texas MD Anderson Cancer Center, between October 2019 and May 2024. In one cohort (n = 30), patients with IDH1-mutant disease received azacitidine (AZA)-venetoclax (VEN)-ivosidenib (IVO); in another cohort (n = 30), patients with IDH1-mutant (n = 7) or IDH2-mutant disease (n = 23) received oral decitabine-VEN-IVO/enasidenib. Patients had a median age of 71 years (range = 62–87 years).
Key Findings
In the pooled population, the triplet regimens were well-tolerated, with 60-day mortality observed in one patient (2%); safety profiles were similar to those observed with doublet regimens (hypomethylating agent–venetoclax; isocitrate dehydrogenase doublets).
Composite complete remission was observed in 55 (92%) of 60 patients and overall response (morphologic leukemia-free state or better) was observed in 57 patients (95%).
Composite complete remission rates were 86% among 37 patients with IDH1-mutant disease, 100% among 23 with IDH2-mutant disease, 98% among 43 with nontreated secondary AML (non-tsAML), and 71% among 17 with treated secondary AML (tsAML).
At a median follow-up of 27.4 months, median overall survival had not been reached in the entire population; at 2 years, overall survival was 69% and cumulative incidence of relapse was 24%.
The 2-year overall survival rate was 72% among patients with IDH1-mutant disease, 67% among those with IDH2-mutant disease, 84% among those with non-tsAML, and 34% among those with tsAML.
A total of 32% of patients went on to receive stem cell transplantation.
The investigators concluded: “Given the excellent outcomes of IDH-triplet therapy for newly diagnosed, [intensive chemotherapy]–ineligible IDH-mutant AML, further prospective studies comparing IDH-triplet vs IDH-doublet regimens are warranted.”
Courtney D. DiNardo, MD, MSCE, of the Department of Leukemia, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Institutes of Health, Leukemia and Lymphoma Society, and others. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
