Intensive Versus Non-intensive Therapy for Patients with Newly Diagnosed Acute Myeloid Leukemia (AML)
Bibliographic record
Abstract
Newly approved treatments have increased the options available for patients with acute myeloid leukemia (AML), but have also generated questions concerning the selection of the most appropriate therapy for a given individual (Tables 1 & 2). The trials leading to the approval of these therapies were based on limited genetic data (e.g., cytogenetics, FMS-like tyrosine kinase-3 [FLT3] status) and clinical parameters (e.g., age, comorbidities, therapy, or secondary AML). Data concerning effectiveness or lack of efficacy of a drug or drug regimen in specific AML subgroups is often determined after drug approval. For example, venetoclax (VEN) + azacitidine (AZA) lower intensity therapy (LIT), which is approved for the treatment of patients with newly diagnosed AML deemed ineligible for intensive chemotherapy (IC) or aged >75 years, was found to have limited efficacy in patients with mutated TP53. Despite the regulatory approved indications for VEN‑based LIT, some older and younger patients can be selected for either LIT or IC. Furthermore, with the availability of maintenance therapy after IC16, several important questions have emerged regarding the role of IC in older patients. No published prospective studies have compared IC with LIT in “fit” patients with newly diagnosed AML to inform treatment choice. Two retrospective propensity score matched real‑world data analyses of outcomes in patients with newly diagnosed AML (irrespective of the genetic profile) who received induction with VEN + AZA or IC, indicated no difference in overall survival (OS). However, one study showed improved complete remission (CR) and/or allogeneic hematopoietic stem cell transplant (alloHCT) rates in favour of IC (60.9% vs. 44.2%, P = 0.006 and 18.1% vs. 8.0%, P = 0.012, respectively). Other single‑centre retrospective studies comparing VEN + AZA with IC have yielded conflicting results. None of these studies provided information concerning the use of oral AZA maintenance therapy. The studies did suggest that outcomes may be dependent on specific genetic abnormalities and/or clinical factors. Currently, several Phase 2 trials are comparing VEN + AZA with IC in adult patients with newly diagnosed AML (NCT04801797, NCT05904106, NCT05554406, NCT05554393). Here, two case scenarios will be discussed to highlight issues surrounding treatment choice: a) fit individuals who are ≥75 years with newly diagnosed European LeukemiaNet (ELN)-defined favourable-risk AML and b) IC eligible persons who are ≥18 years with newly diagnosed ELN‑defined poor-risk AML, who require alloHCT in first complete remission (CR1) with curative intent.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".