Idasanutlin MDM2 (Hdm2) inhibitor Treatment of acute myeloid leukemia Hematological cancer therapy

Acute myeloid leukemia (AML) is the most common acute leukemia affecting adults. Its standard therapy has remained unchanged for the past four decades, so there is a need for newer therapies and more individualized treatments that will increase survival. The transcription factor p53, which plays a pivotal role in suppression of tumor development, is tightly controlled by the MDM2 protein. Idasanutlin is an oral, potent and selective MDM2-p53 small-molecule antagonist, with low nanomolar values in binding affinity for MDM2 and in IC50 in antiproliferative assays. In combination with different anticancer drugs, it showed synergism in cancer cellular lines. In a phase I/Ib study, idasanutlin plus cytarabine in AML patients displayed a complete remission rate of 25%, with median duration of response of approximately 6 months. A phase III trial is ongoing to study the efficacy of the combination of idasanutlin with cytarabine in relapsed/refractory AML patients. Orphan drug designation was granted in the U.S. and E.U. for the treatment of AML.