Dr. Sekeres on the Need for Novel Combinations in Higher-Risk MDS/CMML and Low-Blast AML

Mikkael A. Sekeres, MD, professor of medicine, director, Leukemia Program, Cleveland Clinic Taussig Cancer Institute, discusses the need for novel combinations in higher-risk myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (LB AML).

Patients with higher-risk MDS/CMML and oligoblastic AML (less than 30% blasts) typically receive 1 of 2 treatment regimens: intensive induction chemotherapy or less intensive treatment with a hypomethylating agent. High-intensity treatment has a high treatment-related mortality rate and is cumbersome for older patients with comorbidities, says Sekeres, and less intensive treatment with azacitidine alone results in relatively low and short-lived responses.

As such, investigators launched a phase 2 trial (NCT02610777) which evaluated the addition of pevonedistat, the first and only small-molecule inhibitor of the NEDD8-activating enzyme, to azacitidine in patients with higher-risk MDS/CMML and LB AML. The results were presented in an oral presentation at the 2020 ASCO Virtual Scientific Program.