Dr. Miklos on the Safety Profile of 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 safety profile of KTE-X19 in mantle cell lymphoma (MCL).

In February 2020, the FDA granted a priority review designation to a biologics license application for the investigational CAR T-cell therapy KTE-X19 in patients with relapsed/refractory MCL, based on data from the phase II ZUMA-2 trial.

The toxicities experienced by those who received KTE-X19 in ZUMA-2 were as significant as the toxicities observed in the ZUMA-1 trial, says Miklos; these events included grade ≥3 neurotoxicity and similar levels of grade 2 cytokine release syndrome (CRS), which was reported in at least 50% of patients, adds Miklos. Additionally, cytopenias and low blood cell counts developed in approximately half of the patients at day 28 or beyond.

Three known toxicities commonly associated with CD19-directed CAR T-cell therapies include CRS, neurotoxicity, and cytopenias, and these adverse events (AEs) continue to complicate the treatment of this patient population; however, these AEs are not any worse than those that have already been experienced in this space, says Miklos. An experienced transplant CAR T-cell therapy center will find these toxicities to be very manageable. However, even at these experienced centers, KTE-X19 will be an in-patient therapy that requires an “all-hands-on-deck” attitude to deliver favorable outcomes to patients, concludes Miklos.