John Mascarenhas, MD, Icahn School of Medicine at Mount Sinai, New York, NY, discusses the initial results of a study (NCT03287245) aiming to evaluate the safety and efficacy of idasanutlin, an oral MDM2 inhibitor, in patients with hydroxyurea resistant polycythemia vera (PV), including those who have previously failed ruxolitinib therapy. Drug activity was observed, however, gastrointestinal (GI) toxicity became a limiting factor for many patients after a few cycles of therapy. While idasanutlin will likely not move forward in clinical development in PV, other drugs aiming to upregulate p53 activity via MDM2 inhibition are being investigated. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.