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 < 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 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 | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".