Biomarker Brings Simpler TP53 Status Evaluation, Stronger Survival Prediction in MDS

By Andrew Moreno - Last Updated: October 4, 2024

Biallelic TP53 inactivation is associated with worse survival outcomes in patients with myelodysplastic syndromes (MDS); however, cytogenic testing for the multi-hit TP53 allelic status associated with negative prognoses is not available in all centers. A TP53 variant allele frequency (VAF) threshold of 24% can inform MDS prognosis equally as well as TP53 allelic status, according to a study presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology in Houston, Texas.

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“This parameter offers a simpler approach in the clinical setting in centers where advanced diagnostics are not available,” wrote Luca Rigodanza, MD, of the University of Florence in Italy, and colleagues.

The investigators analyzed publicly available data of 2,496 patients from the Molecular International Prognostic Scoring System study led by Elsa Bernard, PhD, of Memorial Sloan Kettering Cancer Center in New York. They performed receiver operating characteristic (ROC) analysis to identify an optimal TP53 VAF threshold to discriminate mono- from multi-hit allelic status. They also conducted Cox proportional hazards modeling to correlate VAF threshold with overall survival (OS) and leukemia-free survival (LFS), then compared that with the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) standard that VAF of at least 50% can be used as a surrogate for definition of multi-hit status.

The ROC analysis showed that a TP53 VAF of at least 24% adequately predicted multi-hit status, with an area under the curve of 0.81, sensitivity of 0.8, and specificity of 0.74. They also determined from the Cox proportional hazards model that the 24% VAF threshold is a stronger predictor for OS and LFS than the WHO and ICC standard of 50%.

Patients with MDS and TP53 VAF of at least 24% had survival outcomes similar to patients with MDS and confirmed TP53 multi-hit status, with median OS of 0.77 years and 0.76 years, respectively, and median LFS of 0.65 years and 0.64 years, respectively.

In patients with TP53 VAF of less than 24% and patients with single-hit TP53, OS was similar at 2.52 years versus 2.24 years respectively, as was LFS at 2.2 versus 2.2 years, respectively.

“The TP53 24% VAF threshold seems to exhibit the same prognostic power as TP53 allelic status for OS and LFS across distinct [Revised International Prognostic Scoring System] categories, achieving statistical significance in all but low- and high-risk categories,” Dr. Rigodanza and colleagues concluded.

Reference

Rigodanza L, Andreossi G, Consagra A, et al. TP53 VAF as an easier prognostic indicator in myelodysplastic neoplasms in comparison with TP53 allelic status. Abstract #MDS-679. Presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology; September 4-7, 2024; Houston, Texas.

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