Dr. Pemmaraju on the Challenges of Targeting TP53 Mutations in MDS/AML

Naveen Pemmaraju, MD, associate professor in the Department of Leukemia of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses the challenges of targeting TP53-mutant myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

TP53 mutations are present in up to half of patients with solid and liquid tumors, says Pemmaraju. However, the aberrations have been historically difficult to target.

Although some success has been made in indirectly targeting the TP53 axis, these mutations continue to be associated with poor prognosis across hematologic malignancies, explains Pemmaraju.

On January 30, 2020, the FDA granted a breakthrough therapy designation to the combination of APR-246 and the hypomethylating agent azacitidine for the treatment of patients with MDS with a susceptible TP53 mutation. Moreover, a phase 3 clinical trial evaluating the combination in TP53-mutant patients with MDS completed accrual on June 3, 2020.

While the data are still early, the combination appears promising in targeting TP53 mutations in this high-risk patient population, concludes Pemmaraju.