Decitabine-cedazuridine in patients with MDS and TP53 mutations

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Myelodysplastic syndromes (MDS) with TP53 mutations are associated with poor prognosis.
• TP53 mutations represent a significant challenge in MDS treatment outcomes.

Purpose of the Study:

• To evaluate the efficacy of decitabine-cedazuridine (DEC-C) in patients with TP53-mutated MDS.
• To compare outcomes of TP53-mutated MDS patients treated with DEC-C versus parenteral hypomethylating agents (HMA).

Main Methods:

• Analysis of patients from phase 2/3 studies of DEC-C in MDS.
• Classification of patients into TP53 wild-type (TP53wt), TP53 single-hit, and TP53 multi-hit groups.
• Propensity score matching to compare DEC-C treated patients with those receiving single-agent parenteral HMA.

Main Results:

• TP53 multi-hit patients showed a higher incidence of complex cytogenetics and fewer co-mutations.
• TP53 multi-hit patients had a higher rate of lack of response and earlier loss of response.
• Median overall survival was significantly lower for TP53 multi-hit patients compared to TP53 single-hit and TP53wt.
• Propensity-matched analysis showed improved median survival for DEC-C (13.1 months) versus parenteral HMA (8.0 months) in TP53-mutated MDS.

Conclusions:

• TP53 mutation status, particularly multi-hit mutations, impacts response and survival in MDS.
• DEC-C demonstrates potential to improve overall survival in TP53-mutated MDS patients compared to standard parenteral HMA.
• Further investigation into DEC-C efficacy in specific TP53 mutation contexts within MDS is warranted.