https://orcid.org/0000-0003-4634-2279
Key Points
Patients with MDS and TP53 mutations treated with oral decitabine had a longer survival compared to those treated with parenteral HMA.
Duration of response in patients treated with oral decitabine is shorter in patients with multi-hit TP53 mutations compared to single-hit.
Patients with myelodysplastic syndromes (MDS) harboring TP53 mutations have poor outcomes. The objective of this study is to evaluate patients with TP53 mutations treated in the phase 2/3 studies of decitabine-cedazuridine (DEC-C) in MDS. We divided patients into three groups: TP53wt, TP53single-hit, and TP53multi-hit. We then performed propensity matching of patients who were treated with DEC-C vs a cohort of patients treated with parenteral hypomethylating agents (HMA). 180 patients were analyzed of which 73 (40.5%) had TP53 mutations, 23 (12%) with TP53multi-hit. Patients with TP53multi-hit more frequently had 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). Patients with TP53multi-hit had a higher chance of lack of response with 39.1% vs 28.1% for TP53single-hit (p=0.2). Patients with TP53mult-hit lost response earlier at 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 (log-rank, p < 0.005). Propensity scores matched 47 TP53mutpatients treated with DEC-C and 47 TP53mut patients treated with single agent parenteral HMA. Median survival was 13.1 months (95% CI: 8.4 - 21.3) for DEC-C vs 8.0 months (95% CI: 5.2 - 13.0) for single agent parenteral HMA (log-rank, p=0.047). In patients with MDS harboring TP53mut, DEC-C may improve overall survival compared to parenteral HMA.
