Therefore, we performed an investigator-initiated phase 1 trial of the oral MDM2 antagonist idasanutlin (RG7388; Roche) in patients with high-risk PV/ET for whom at least 1 prior therapy had failed.
In polycythemia vera, a novel interferon administered every 2 weeks is being developed for front-line therapy in high-risk individuals, and inhibitors of human double minute 2 (HDM2) have shown promise in preclinical studies, as have HDAC inhibitors such as givinostat (both in the laboratory and in the clinic).
To permit the long-term use of IFN, we propose combining low doses of IFN with Nutlin-3, an antagonist of MDM2, which is also capable of promoting PV CD34(+) cell apoptosis.
Samples of PV and ET analyzed in chronic phase disease were consistently devoid of all genetic lesions tested, suggesting that alterations of TP53, NRAS, KRAS, and MDM2 do not contribute significantly to development of chronic phase PV and ET.