Dr. DiPersio on Investigational Targeted Cellular Therapies in AML

John F. DiPersio, MD, PhD, deputy director of the Siteman Cancer Center and professor in the Department of Medicine, Oncology Division, at Washington University School of Medicine in St. Louis, discusses the current state of CAR T-cell therapy, dual affinity re-targeting (DART), bi-specific T-cell engagers (BiTEs), and antibody-drug conjugates (ADCs) for acute myeloid leukemia (AML) treatment.

Gemtuzumab ozogamicin (Mylotarg), an ADC, is approved by the FDA and there are a number of others that are in development targeting myeloid antigens, such as CD33 or CD123, explains DiPersio. Additionally, there are a number of physicians interested in CARs, BITEs, and DARTs. The response rates have been modest, but do not come close to comparing with the outcomes of obinutuzumab (Gazyva) or CARs for acute lymphocytic leukemia, according to DiPersio.

DiPersio would argue that the reason treatments for AML are lagging behind other hematologic diseases is the choice of targets may not be ideal. The targets currently used are expressed widely in other cells, including maturing myeloid cells, especially monocytes, which are the cells that create the chemokines and cytokines that cause cytokine release syndrome (CRS). Currently, patients with relapsed AML who will undergo transplant get modest response rates, but improvements are necessary, says DiPersio. One method to improve response rates is to use checkpoint inhibitors, which will hopefully make the treatment work better but will exacerbate CRS. Another option is to find a better way to mitigate CRS in order to increase the dose of the drugs, concludes DiPersio.