Frederick Lock, MD, spoke about how future research regarding axicabtagene ciloleucel for patients with large B-cell lymphoma will progress.
Frederick Locke, MD, vice chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy as well as program co-leader of Immuno-Oncology at Moffitt Cancer Center in Tampa, Florida, spoke to CancerNetwork® about further research of axicabtagene ciloleucel (Yescarta; axi-cel) for patients with large B-cell lymphoma (LBCL).1 Axi-cel was recently approved for patients pretreated with chemoimmunotherapy in the frontline setting and who relapsed within 12 months based on the phase 3 ZUMA-7 trial (NCT03391466) which compared axi-cel with standard of care therapy.2
Axi-cel is a CAR T-cell therapy and one of the things that we don’t fully understand is why does CAR T-cell therapy does not work for more patients [with LBCL]. It targets CD19 on the surface of the cells, but the loss of CD19 does not seem to be a dominant mechanism for the tumor to evade CAR T-cell therapy. We need to figure out why patients progress even though they’ve been given CAR T-cell therapy. Once we understand that, we can design better CAR T-cell therapies. There are other ways to intervene, that includes either dual targeting against not just CD19, but other targets on the cell surface. We’re also looking at off-the-shelf or allogenic donor CAR T-cells which can be accessed easier and be given to the patient quicker. We’re looking at other strategies using other natural killer cells and gamma delta T-cells with other ways to get therapy quickly to the patients that can work best.