Novel Therapies Needed to Improve TP53-mutant AML Outcomes
Patients with acute myeloid leukemia (AML) harboring mutations in the tumor protein 53 (TP53) gene have worse complete remission rates and durations and overall survival regardless of age or the type of treatment received, a study published in the journal Cancer has shown.1
Because TP53 mutations predict a poor prognosis in patients with AML, researchers sought to evaluate clinicomolecular characteristics, response to therapy, and outcomes in patients with newly diagnosed TP53-mutant AML.
For the study, investigators analyzed peripheral blood or bone marrow samples from 293 patients using targeted, amplicon-based, next-generation sequencing-based analysis. Of those, 53 harbored TP53 mutations.
The study demonstrated that TP53 mutations were significantly more likely to be present in patients who had a complex karyotype, abnormalities of chromosome 5, 7, and 17, and therapy-related AML.
Results showed that compared with the 240 patients with wild-type TP53, those with TP53 mutations had a lower complete remission rate (41% vs 57%; P =.04). In addition, patients with TP53-mutant AML had a significantly inferior 2-year complete remission rate (30% vs 55%; P =.001).
Researchers also found that patients harboring TP53 mutations had significantly poorer overall survival vs patients with wild-type TP53.
Importantly, disparities in outcomes were observed irrespective of whether patients were younger than 60 years or 60 years and older, or whether patients received high-intensity or low-intensity chemotherapy.
The findings ultimately suggest that novel therapies are needed to improve the outcomes of patients with AML who harbor this particular gene mutation.
1. Kadia TM, Jain P, Ravandi F, et al. TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes. Cancer. 2016 Jul 26. doi: 10.1002/cncr.30203. [Epub ahead of print]