Azacitidine Plus APR-246 Appears Promising as Treatment of TP53-Mutant MDS and AML

August 24, 2020

Thomas Cluzeau, MD, PhD, discusses the rationale for evaluating azacitidine in combination with APR-246 in patients with TP53-mutant myelodysplastic syndrome and acute myeloid leukemia.

Thomas Cluzeau, MD, PhD, head of hematology department, Central University Hospital of Nice, in Nice, France, discusses the rationale for evaluating azacitidine in combination with APR-246 as treatment of patients with TP53-mutant myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).

TP53 mutations occur in about 5% to 10% of patients with MDS and AML, and it is more in common in AML, says Cluzeau. These patients tend to have a very poor prognosis with a low rate of complete responses with azacitidine alone, as well as a short median overall survival of 6 to 9 months.

APR-246 may change the conformation of TP53 mutations and wild-type TP53. The TP53 pathway becomes functional, and apoptosis could be used in this cell after treatment with APR-246. In vitro and in vivo analyses have demonstrated a synergistic effect with the combination of azacitidine and APR-246, which is why investigators evaluated this treatment in a phase 2 study.

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