Dr. Perl on Challenges of Implementing Immunotherapy in AML

Alexander E. Perl, MD, MS, associate professor of medicine, Perelman School of Medicine, University of Pennsylvania, discusses the challenges of using immunotherapy with antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and CAR T-cell therapies in acute myeloid leukemia (AML).

Currently, the main ADC that is being used in clinical practice is gemtuzumab ozogamicin (Mylotarg), which is approved for the treatment of adult patients with newly diagnosed CD33-positive AML, says Perl. However, other potential agents are in early development and are being used exclusively in clinical trials, adds Perl.

Specifically, bispecific antibodies are showing promise in this space; however, questions regarding optimal targets, payload, and drug delivery still need to be answered.

CAR T-cell therapy has shown success in acute lymphoblastic leukemia (ALL), but are much harder to create in AML. The myeloid blasts, the tumor cells in AML, are shared with normally-occurring hematopoietic elements in healthy cells, Perl explains. An agent that effectively kills those cells may result in increased extramedullary or marrow toxicity against normal cells that you might wish to preserve, concludes Perl.