P552: TREATMENT OUTCOMES IN NEWLY DIAGNOSED, UNTREATED PATIENTS WITH TP53-MUTATED ACUTE MYELOID LEUKEMIA: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS
Bibliographic record
Abstract
Background:TP53 mutations are present in 10% to 15% of patients with acute myeloid leukemia (AML) and are associated with resistance to therapy and poor outcomes. Currently available frontline therapies for TP53-mutated AML include intensive chemotherapy (IC), hypomethylating agents (HMAs), and venetoclax combined with HMA (VEN+HMA). Aims: To describe response and survival outcomes associated with IC, HMAs, and VEN+HMA in newly diagnosed, untreated patients with TP53-mutated AML. Methods: EMBASE and MEDLINE were systematically searched to identify prospective and retrospective studies that reported complete remission (CR), CR with incomplete hematologic recovery (CRi), median overall survival (OS), event-free survival (EFS), or duration of response (DOR) outcomes in patients with TP53-mutated AML treated with IC, HMAs, or VEN + HMA. Screening and data extraction were conducted independently and in duplicate by 2 reviewers. Response outcomes (CR and CRi) were pooled using random-effects models, and the median of medians method was used for time-related outcomes (OS, EFS, DOR). Results: From the 3006 abstracts identified (May 20, 2021), 17 publications (12 studies: 6 randomized controlled trials, 2 single-arm trials, and 4 retrospective studies) satisfied the inclusion criteria (Table). The percentage of patients achieving CR was highest with IC (43%; 95% CI, 30%-56%; N=133), followed by VEN+HMA (33%; 95% CI, 22%-47%; N=54;) and HMA (21%; 95% CI, 7%-49%; N=14). The CRi rate was highest with VEN+HMA (20%; 95% CI, 12%-33%; N=54), followed by IC (6%; 95% CI, 1%-20%; N=35). No studies reported CRi outcomes for HMA alone. The rates of CR/CRi were 49% (95% CI, 37%-60%; N=121) for VEN+HMA, 46% (95% CI, 39%-53%; N=200) for IC, and 13% (95% CI, 2%-48%; N=28) for HMA alone. The median OS was similarly low across the 3 treatments: 6.5 months for IC (95% CI, 5.1-8.5 months; N=155), 6.2 months for VEN+HMA (95% CI, 5.2-7.2 months; N=73), and 6.1 months for HMA (95% CI, 4.9-7.2 months; N=34). The median EFS was 3.7 months (95% CI, 1.6-5.7 months; N=133) with IC. The median DOR was 3.5 months (N=35) with IC and 5.0 months (95% CI, 3.5-6.5 months; N=54) with VEN+HMA. No studies reported EFS for HMA alone or VEN+HMA or DOR for HMA alone. Table. - Outcomes in newly diagnosed, untreated adult patients with TP53-mutated AML treated with IC, HMA, and VEN+HMA ICstudies Total, N Outcome(95% CI) HMAstudies Total, N Outcome(95% CI) VEN+HMAstudies Total, N Outcome(95% CI) CR rate 2 133 0.43(0.30-0.56) 1 14 0.21(0.07-0.49) 2 54 0.33(0.22-0.47) CRi rate 1 35 0.06(0.01-0.2) 0 - - 2 54 0.20(0.12-0.33) CR/CRi rate 4 200 0.46(0.39-0.53) 2 28 0.13(0.02-0.48) 4 121 0.49(0.37-0.60) Median OS, months 3 155 6.5(5.1-8.5) 2 34 6.1(4.9-7.2) 2 73 6.2(5.2-7.2) Median EFS, months 2 133 3.7(1.6-5.7) 0 - - 0 - - Median DOR, months 1 35 3.5(not reported) 0 - - 2 54 5.0(3.5-6.5) Summary/Conclusion: CR, CR/CRi, DOR, and median OS were modest across all treatments for newly diagnosed, untreated patients with TP53-mutated AML. Limitations of this analysis include low study and patient numbers for some interventions, the lack of direct trial comparisons, and that CR/CRi outcomes were not reported separately for DOR. The findings of this review highlight the significant unmet need for this very difficult-to-treat population.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.001 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".