Oral Decitabine/Cedazuridine in Patients with MDS and <i>TP53</i> Mutations: A Propensity Score Matching Analysis from the Phase II and III Trials
Bibliographic record
Abstract
Patients with myelodysplastic syndrome harboring TP53 mutations have poor outcomes. Decitabine/cedazuridine has been suggested to have activity in TP53mut MDS. This study evaluates decitabine/cedazuridine in TP53mut MDS treated in the phase 2 and 3 studies that led to the FDA approval of these drugs. Using the WHO 2022 classification, we divided patients into three groups: TP53wt, TP53single-hit, and TP53multi-hit. A total of 180 patients were analyzed of which 73 (40.5%) had TP53 mutations, 23 with TP53multi-hit. Patients with TP53multi-hit were enriched for complex cytogenetics (69.5%), and had fewer median number of co-mutations (2.5, IQR 2-3) compared to TP53single-hit(3, IQR 1-5), or TP53wt (4, IQR 3-6) (p=0.002). Complete response rates were similar between these groups, but patients with TP53multi-hit had a relatively higher likelihood of lack of response with 39.1% vs 28%, and 27.1% for TP53single-hit, and TP53wt, respectively (p = 0.2). Patients with TP53multi-hit also received fewer courses of therapy due to progression, 5 vs 7.5 for TP53single-hit, and 9 for TP53wt (p =0.016). Patients with TP53mult-hit lost response earlier with 8.2 months, vs 13.2 months for TP53single-hit, and 15.1 months for TP53wt (p=0.1). Median overall survival (mOS) was 11.5 months (95% CI: 8.6 - 19.1) for TP53mult-hit, 22.1 months (95% CI: 14.6 - 35.9) for TP53single-hit, and 31.7 months (95% CI: 19.5 - 51.1) for TP53wt MDS (log-rank, p &lt; 0.005). With a median follow-up time of 21.5 months, at a landmark analysis of 4 months, hematopoietic stem cell transplantation (HSCT) did not result in improved survival. A propensity score matched 47 patients treated with decitabine/cedazuridine and TP53mut were matched to 47 with MDS and TP53mut treated with single agent IV hypomethylating agent (HMA) using age, ECOG performance status, IPSS-R scores, and TP53 VAF as matching features. Median overall survival was 13.1 months (95% CI: 8.4 - 21.3) for decitabine/cedazuridine vs 8.0 months (95% CI: 5.2 - 13.0) for single agent IV HMA (log-rank, p=0.047). In patients with MDS harboring TP53mut, decitabine/cedazuridine may improve survival compared to conventional single-agent IV HMA.
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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 | 0.000 |
| 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 | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".