MDM2 Inhibitor May Improve Response in AML

Ariela Katz
Published: Monday, Jul 09, 2018
Marina Konopleva, MD

Marina Konopleva, MD
Investigators are hopeful that idasanutlin, a novel small molecule that targets the MDM2 protein, can improve the efficacy of chemotherapy in patients with relapsed/refractory acute myeloid leukemia (AML). This agent is being tested in combination with cytarabine, which is commonly used as a first or second salvage therapy in this patient population.

“Relapsed AML is a difficult disease to tackle, especially because salvage therapy response rates drop from about 75% in newly diagnosed patients to 40% in the first salvage population and the second salvage population [has response rates of] about 15% to 20%, so it’s hard to cure anybody at this stage,” said Marina Y. Konopleva, MD, PhD, professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston.

The international phase III MIRROS clinical trial (NCT02545283) is currently enrolling patients with relapsed/refractory AML, according to Konopleva, who is the principal investigator at MD Anderson. Participants must have experienced 1 or 2 relapses. They also must have received no more than 2 prior induction regimens, and 1 or both must have included cytarabine with an anthracycline. Those who qualify will be randomized to either idasanutlin with cytarabine or cytarabine with a placebo (Figure).

Figure. Idasanutlin With Cytarabine in Relapsed/Refractory AML

Notably, the primary endpoint is overall survival (OS) and will be assessed in a subset of the patient population with TP53 wild type, with OS in the overall population as a secondary endpoint. Assessing the TP53 wild-type population as the primary endpoint is important because idasanutlin’s mechanism of action depends on p53, which is encoded by TP53.

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