Decitabine Plus Cedazuridine in TP53-Mutated MDS: Survival Compares Favorably With HMA

Combination decitabine plus cedazuridine has been approved by the US Food and Drug Administration (FDA) for use in TP53-mutated myelodysplastic syndromes (MDS).

A team of researchers led by Samuel Urrutia, MD, of the University of Texas MD Anderson Cancer Center in Houston, has evaluated the phase II and III studies that factored into the FDA’s approval and presented their findings at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

This evaluation incorporated data from 180 patients with MDS. Among them were 73 patients with TP53 mutations, whom the team divided into three groups: wild type TP53, single-hit TP53, and multi-hit TP53.

Median overall survival (OS) among the three groups was shortest in the multi-hit TP53 group at 11.5 months, followed by the single-hit group at 22.1 months, and the wild-type group at 31.7 months (log-rank, P< .005).

Complete response to the combination therapy was similarly prevalent across the three groups, but the percentage of patients with lack of response was highest in the multi-hit group at 39.1%, followed by the single-hit group at 28.0%, and the wild-type group at 27.1% (P=.2). Response loss also occurred soonest in the multi-hit group, at 8.2 months compared with 13.2 months in the single-hit group and 15.1 months in the wild-type group (P=.1).

The researchers also used propensity scoring to match 47 patients with TP53 mutation treated with decitabine plus cedazuridine with 47 patients with TP53 mutation who received single agent IV HMA. They calculated median OS to be 13.1 months in patients who received the combination versus 8.0 months in patients who received an HMA (log-rank, P=0.047).

The team concluded that in this clinical setting, “decitabine/cedazuridine may improve survival compared to conventional single-agent [intravenous (IV) hypomethylating agent (HMA)].”

Reference

Urrutia S, Sasaki K, Bataller A, et al. Oral decitabine/cedazuridine in patients with MDS and TP53 mutations: A propensity score matching analysis from the phase II and III trials. Abstract #661. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.