The variant allele frequency of mutant TP53 “provides important prognostic information” in patients with newly diagnosed TP53-mutated acute myeloid leukemia (AML), according to a retrospective study.
Nicholas Short, MD, of the MD Anderson Cancer Center, and colleagues conducted the research and published their findings in Blood Advances.
They conducted the research because “the prognostic impact of mutant TP53 variant allelic frequency is not well established, nor is how this information might guide optimal frontline therapy.”
Dr. Short and colleagues retrospectively analyzed 202 patients with newly diagnosed TP53-mutated AML who received first-line therapy with a cytarabine-based regimen or a hypomethylating agent-based regimen.
A mutant TP53 variant allele frequency of >40% was independently associated with a significantly higher cumulative incidence of relapse (P=.003). Having a mutant TP53 variant allele frequency of >40% was also associated with significantly worse relapse-free survival (P=.001) and overall survival (OS; P=.003).
However, the impact of mutant TP53 variant allele frequency on clinical outcomes was “driven by patients treated with a cytarabine-based regimen,” Dr. Short and colleagues wrote.
In patients who received a cytarabine-based regimen, the median OS was 4.7 months in those with a variant allele frequency of >40%, while it was 7.3 months in those with a variant allele frequency of ≤40% (P=.006). The variant allele frequency did not significantly affect OS in patients who received a hypomethylating agent.
Adding venetoclax to a hypomethylating agent did not significantly impact OS compared to a hypomethylating agent alone. This was true for the entire population of patients with TP53 mutations and in those stratified by mutant TP53 variant allele frequency.
Of the patients with a mutant TP53 variant allele frequency of ≤40%, the OS was “superior” in those receiving higher dose cytarabine, the study’s authors wrote. However, the OS was “similarly poor” regardless of therapy for those with a mutant TP53 variant allele frequency >40%, according to Dr. Short and colleagues.
Patients with one TP53 mutation with a variant allele frequency of ≤40% who received a frontline cytarabine-based regimen had the “best long-term outcomes,” with a two-year OS rate of 38%, compared with a two-year OS rate of 6% for all others (P<.001), the researchers wrote.
“In summary, TP53 [mutation variant allele frequency] provides important prognostic information that may be considered when selecting frontline therapy for patients with newly diagnosed TP53-mutated AML,” Dr. Short and colleagues concluded.
Short NJ, Montalban-Bravo G, Hwang H, et al. Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia. Blood Adv. 2020;4(22):5681-5689. doi:10.1182/bloodadvances.2020003120