Transient expansion of TP53 mutated clones in polycythemia vera patients treated with idasanutlin.

ABSTRACT: Activation of the P53 pathway through inhibition of MDM2 using nutlins has shown clinical promise in the treatment of solid tumors and hematologic malignancies. There is concern, however, that nutlin therapy might stimulate the emergence or expansion of TP53-mutated subclones. We recently published the results of a phase 1 trial of idasanutlin in patients with polycythemia vera (PV) that revealed tolerability and clinical activity. Here, we present data indicating that idasanutlin therapy is associated with expansion of TP53 mutant subclones. End-of-study sequencing of patients found that 5 patients in this trial harbored 12 TP53 mutations; however, only 1 patient had been previously identified as having a TP53 mutation at baseline. To identify the origin of these mutations, further analys

SUBMITTER: Marcellino BK 

PROVIDER: S-EPMC7686898 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature