Dr. Miklos on Development Process for KTE-X19 in MCL

David Miklos, MD, associate professor of medicine, Blood and Marrow Transplantation, and clinical director of Cancer Cell Therapy at Stanford University Medical Center, discusses the process of developing KTE-X19 and the ZUMA-2 trial in mantle cell lymphoma (MCL).

The pharmaceutical company Kite Pharma, a subsidiary of Gilead Sciences, introduced axicabtagene ciloleucel (axi-cel; Yescarta) to the treatment paradigm for diffuse large b-cell lymphoma, says Miklos. Using the same construct of targeting CD19 with a CD28 costimulatory domain as axi-cel, KTE-X19 was produced; however, it is important to note the difference that they are isolating T-cells using CD4-positive/CD8-positive infinity isolation and then making products that are specific to T-cells. This was the conversion; it was the important process of evolution for the ZUMA-2 trial in patients with MCL who had failed 2 prior lines of therapy and were either ibrutinib (Imbruvica)-refractory or ibrutinib-intolerant, adds Miklos.

At the 2019 ASH Annual Meeting and the 2020 TCT Meetings, Michael Wang, MD, of The University of Texas MD Anderson Cancer Center, who is the lead author on the study, shared data from ZUMA-2. At Stanford University, investigators were very enthusiastic to bring these patients forward. This is a challenging patient population because once ibrutinib fails them, venetoclax (Venclexta) and other therapies are available, but no long-term remissions are observed, concludes Miklos.