Does TP53 Status Influence CCUS Outcomes?

A recent study evaluated if the TP53 mutation status in clonal cytopenia of undetermined significance (CCUS) impacts the risk of mortality or progression to a myeloid neoplasm such as myelodysplastic syndromes (MDS).

Syed Naseem Shah, MD, of the Mayo Clinic and colleagues conducted the study and presented their findings at the 2023 American Society of Clinical Oncology Annual Meeting.

A subset of TP53-mutated myeloid neoplasms, such as MDS, are preceded by TP53-mutated CCUS, which is “conventionally considered to be a high-risk premalignant condition, though evidence supporting the notion is lacking,” according to Dr. Shah and colleagues.

They queried the Mayo Clinic Molecular Hematology Database (n=7,593) to identify patients who harbored pathogenic variants in exons four through 11 of the TP53 gene with ≥2% variance allele frequency (VAF).

They identified 457 patients with mutated TP53, finding that 29 (5.9%) had TP53-mutated CCUS. The median patient age at diagnosis was 67 years and 59% of patients were female. Most of the patients (69%) received cytotoxic therapies. Nearly all patients (89.6%) with TP53-mutated CCUS had a single TP53 mutation, while 10.3% had two or more TP53 mutations. The median VAF of mutated TP53 was 9%, with three patients having a median VAF of 20% or more.

In the 16 patients who had available follow-up evaluation data at a median interval of 22 months, three (10.3%) progressed to develop a TP53-muated myeloid neoplasm. One of the progressions occurred at five months after diagnosis, while the other two progressions occurred at 13 and 14 months after diagnosis.

The researchers also compared outcomes of patients with TP53-mutated CCUS to the outcomes of those with wild-type TP53 CCUS (n=138). There were no significant differences between groups in the proportion of patients who developed a myeloid neoplasm (18.1% and 10.3%, respectively; P=.42).

The progression-free survival (PFS) and overall survival (OS) rates of patients with TP53-mutated CCUS were “comparable” to those with wild-type TP53 CCUS, according to the study’s authors. See TABLE 1 for PFS rates. See TABLE 2 for OS rates.

TABLE 1. PFS Rates by TP53 Status

TABLE 2. OS Rates by TP53 Status.

“In contrast to the prevalent notion, TP53 [mutation] was not associated with a higher risk of [myeloid neoplasm] progression or mortality compared to [wild-type] TP53 CCUS,” Dr. Shah and colleagues concluded. “[The] majority of TP53 [mutated] clones showed remarkable stability over years.”

Reference

Shah SN, Li M, Baranwal A, et al. Outcome of TP53-mutated CCUS and the risk of progression to myeloid neoplasms. Abstract #7059. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.