CPX-351 versus venetoclax plus hypomethylating agents for newly diagnosed acute myeloid leukemia: A systematic review and meta-analysis
Bibliographic record
Abstract
Abstract Introduction: Acute myeloid leukemia (AML) is one of the most common types of acute leukemia. Since the median age at diagnosis is 68 years, selecting an appropriate treatment strategy is important for older adults who are ineligible for standard 7+3 regimen. Recently, CPX-351 demonstrated superior overall survival (OS) compared to standard 7+3 chemotherapy in older adults with secondary AML, while the combination of venetoclax and azacitidine has shown greater efficacy than azacitidine alone in older adults with AML. However, in real-world clinical practice, it remains unclear which regimen is more appropriate for this population. To address this uncertainty, we conducted a systematic review and meta-analysis to compare the effectiveness of these treatment strategies in patients with AML. Methods: We performed a systematic review and meta-analysis of observational and randomized controlled trials comparing the outcomes in patients with newly diagnosed AML who received CPX-351 versus the combination of venetoclax and hypomethylating agents (Ven/HMA). A comprehensive search of PubMed, Scopus, and Cochrane CENTRAL databases was performed up to June 2025, as well as a manual review of reference lists from relevant articles. This review adheres to the recommendations from the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines. R software version 4.5.1 was used for statistical analyses. Results: A total of 1,807 patients from nine retrospective studies were included in this systematic review and meta-analysis, comprising 692 patients in the CPX-351 cohort and 1,115 patients in the Ven/HMA cohort. The median age was 64.5 years in the CPX-351 cohort and 73 years in the Ven/HMA cohort. The proportion of patients with AML with myelodysplasia-related changes was 58.1% (n = 393) in the CPX-351 group and 37.8% (n = 396) in the Ven/HMA group. Therapy-related AML accounted for 20.6% (n = 96) of patients in the CPX-351 cohort and 16.8% (n = 138) in the Ven/HMA cohort. Patients classified as favorable or intermediate risk according to the European LeukemiaNet 2017 risk stratification accounted for 29.2% (n = 203) in the CPX-351 cohort and 23.5% (n = 269) in the Ven/HMA cohort. Two studies provide the result of multivariate analyses for OS. As a result, the pooled hazard ratio (HR) favored CPX-351 for OS, but this difference did not reach statistical significance (HR 0.88; 95% CI 0.75-1.03; p = 0.1195; I2 = 0.0%). There was no significant difference in the rates of complete remission (CR) or complete remission with incomplete count recovery (CRi) between the two groups (odds ratio [OR] 0.83; 95% CI 0.58-1.18; p = 0.295; I² = 52.6%). Conclusions: In patients with newly diagnosed AML, CPX-351 did not demonstrate superiority over Ven/HMA in terms of CR/CRi rates. While OS appeared to favor CPX-351, the difference was not statistically significant and we could not reject the null hypothesis. These findings, especially the trend toward improved OS with CPX-351, underscore the need for further prospective studies to more clearly identify the optimal induction therapy for older adults with AML.
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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 | 0.011 | 0.025 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.037 |
| Bibliometrics | 0.005 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".