Dr. Pollyea on Emerging Therapies in Higher-Risk Myelodysplastic Syndrome

Daniel Pollyea, MD, MS, associate professor of medicine/hematology, University of Colorado (UC) Medicine, clinical director, Leukemia Services, UCHealth Blood Disorders and Cell Therapies Center, UCHealth, discusses emerging therapies in higher-risk myelodysplastic syndrome (HR-MDS).

Venetoclax (Venclexta) in combination with azacitidine demonstrated promising early efficacy in patients with newly diagnosed and relapsed/refractory MDS in the phase 1b M15-531 study (NCT02942290), Pollyea says. Based on these results, on July 21, 2021, the FDA granted a breakthrough therapy designation to the combination of venetoclax plus azacitidine for the treatment of patients with previously untreated intermediate-, high-, and very high-risk MDS per the revised International Prognostic Scoring System.

Pevonedistat is another emerging option for patients with newly diagnosed HR-MDS, Pollyea says. Findings from the randomized phase 2 Pevonedistat-2001 study (NCT02610777) demonstrated improved median event-free survival and overall survival with the combination of pevonedistat/azacitidine vs azacitidine alone in patients with HR-MDS/chronic myelomonocytic leukemia and low-blast acute myelogenous leukemia. Based on these data, the FDA granted pevonedistat a breakthrough therapy designation for the treatment of patients with HR-MDS. 

Finally, magrolimab, a CD47-directed antibody, has also demonstrated promising preliminary efficacy in an ongoing phase 1b trial (NCT03248479) in patients with newly diagnosed MDS, Pollyea says. The agent was granted a breakthrough therapy designation by the FDA in September 2020 for use in that patient population.

These agents have the potential to advance the treatment paradigm of patients with MDS and expose some of the vulnerabilities of the disease for use in future research efforts, concludes Pollyea.