Faculty, Staff and Student Publications
Language
English
Publication Date
10-28-2025
Journal
Blood Advances
DOI
10.1182/bloodadvances.2025016399
PMID
40706052
PMCID
PMC12550153
PubMedCentral® Posted Date
7-28-2025
PubMedCentral® Full Text Version
Post-print
Abstract
In the phase 3 AGILE study, after a 12.4-month median follow-up, ivosidenib, a mutant isocitrate dehydrogenase 1 (IDH1) inhibitor, combined with azacitidine significantly improved event-free survival, overall survival (OS), and complete remission rates compared with placebo-azacitidine in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML), who were unfit for intensive chemotherapy. This post hoc analysis reports long-term follow-up results from AGILE after a median follow-up of 28.6 months. Overall, 148 patients were randomized to receive ivosidenib-azacitidine (n = 73) or placebo-azacitidine (n = 75). Median OS was significantly longer with ivosidenib (29.3 months; 95% confidence interval [CI], 13.2 to not reached) than with placebo (7.9 months; 95% CI, 4.1-11.3; hazard ratio, 0.42 [95% CI, 0.27-0.65]; P < .0001). Hematologic recovery was faster, more durable, and conversion to transfusion independence (53.8% vs 17.1%; P = .0004) was more common with ivosidenib than with placebo. Of 33 ivosidenib-treated patients evaluable for molecular measurable residual disease (MRD), 10 converted to MRD negativity. Although OS did not differ significantly between MRD-negative and MRD-positive responders at the 0.1% variant allele frequency (VAF) threshold, MRD-negative patients had numerically longer survival. MRD status appeared more predictive of long-term OS when an exploratory 1% VAF threshold was applied. MRD response was not associated with IDH1 variant, VAF, inferred clonality, or number of baseline comutations. The previously reported safety profile was maintained. These long-term efficacy and safety results confirm the benefit of ivosidenib-azacitidine in this challenging-to-treat population and support its use as a standard of care with the longest reported survival benefit for intensive chemotherapy–ineligible patients with IDH1-mutated AML. This trial was registered at www.ClinicalTrials.gov as #NCT03173248.
Keywords
Humans, Isocitrate Dehydrogenase, Leukemia, Myeloid, Acute, Female, Male, Middle Aged, Glycine, Mutation, Aged, Adult, Azacitidine, Pyridines, Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Follow-Up Studies
Published Open-Access
yes
Recommended Citation
Montesinos, Pau; Marchione, Dylan M; Recher, Christian; et al., "Long-Term Results From the AGILE Study of Azacitidine Plus Ivosidenib vs Placebo in Newly Diagnosed IDH1-Mutated AML" (2025). Faculty, Staff and Student Publications. 5567.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5567
Graphical Abstract
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