Dr. DeAngelo on the Mechanism of Action of Pevonedistat in MDS

Daniel J. DeAngelo, MD, PhD, institute physician, chief, Division of Leukemia, Dana-Farber Cancer Institute, professor of medicine, Harvard Medical School, discusses the mechanism of action of pevonedistat in myelodysplastic syndrome (MDS).

Pevonedistat is a NEDD-8 inhibitor that targets proteins for the proteasome, says DeAngelo. Moreover, the agent has demonstrated utility in combination with chemotherapeutic agents, such as hypomethylating agents (HMAs), DeAngelo explains. HMAs, such as azacitidine and decitabine, are standard options for patients with high-risk MDS because of established response rates; however, these response rates remain low. 

Notably, adding pevonedistat to HMAs does not appear to increase toxicity, DeAngelo says. Moreover, data have shown that combining the agent with HMAs can improve response rates for patients with high-risk MDS. However, confirmatory phase 3 trials are needed to parse out the benefit the combination may yield for patients, concludes DeAngelo.