<i>IDH2</i> mutation is associated with favorable outcome among older adults with newly diagnosed acute myeloid leukemia treated with hypomethylating agent-based therapy
Bibliographic record
Abstract
Mutations of isocitrate dehydrogenase (IDH) are recurrent in newly diagnosed acute myeloid leukemia (AML) and their prevalence increases with age. The prognostic impact of IDH mutations in AML remains controversial. IDH inhibitors generally have a favorable side-effect profile, making them an attractive option for older patients. This retrospective analysis aimed to describe the prevalence and prognostic impact of IDH mutations in a large cohort of newly diagnosed AML patients aged ≥60 years enrolled in the Beat AML clinical trial. A total of 1,023 patients were included. IDH mutations were detected in 28% of patients, including 9.7% with IDH1mut, 18.9% with IDH2mut, and 1.0% with mutations in both IDH1 and IDH2. IDH mutations frequently co-occurred with DNMT3A (38%), NPM1 (35%), and SRSF2 (34%) mutations. In patients treated with intensive chemotherapy, IDH mutations were not prognostic for overall survival (OS) (P=0.76), while OS was longer for patients with IDH2mut compared to IDHwt in patients treated with hypomethylating agent (HMA)-based therapy (median OS, 18.5 vs. 10.2 months, P<0.001). IDH1 was not significant for outcome. IDH2 remained prognostic for OS after exclusion of patients receiving an IDH inhibitor (hazard ratio=0.60, 95% confidence interval: 0.41-0.89). Outcomes with TP53 or myelodysplasia-related gene mutations were also better with an IDH co-mutation (P=0.043, and P=0.006, respectively). In patients treated with HMA plus venetoclax (N=243), IDHmut was not prognostic (P=0.42). The high prevalence of IDHmut and favorable impact in patients treated with HMA-based therapy supports studies investigating the addition of targeted therapies to HMA-based regimens for older patients with IDH-mutant AML; mut: mutated; wt: wild-type.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".