Long-term results from the AGILE study of azacitidine plus ivosidenib vs placebo in newly diagnosed <i>IDH1</i> -mutated AML
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".