The study, “Axicagagene Ciloleucel (CD19 CAR T) in Refractory Large B-Cell Lymphoma,” was led by Sattva Neelapu of the MD Anderson Cancer Center and Frederick Locke of the H. Lee Moffitt Cancer Center and Research Institute.
The CAR-T cell treatment used in the study, is offered by Kite Pharma. Two other companies, Novartis and Juno Therapeutics, are also developing CAR-T Cell therapies.
Based on results of the study, the FDA approved a CAR-T treatment called xicabtagene ciloleucel or Yescarta. The study included 111 patients from 22 centers, including John Theurer Cancer Center. The patients had refractory large B-cell lymphoma -who failed chemotherapy- or patients who relapsed early after stem cell transplantation.
The basis of this new cell therapy is to harness the patient’s own T-cells, or white blood cells that are part of the immune system. T-cells are collected from the patient and sent to the manufacturing lab. There, the cells are genetically modified through introduction of a gene that instructs the cells to target and kill lymphoma cells. These genetically modified T-cells are then expanded in the lab before being infused back into the patient.
In the study, T-cells were successfully produced and expanded in 99 percent of patients. Eighty-four percent of patients responded, with 42 percent of all patients achieving a complete remission. More than half of all patients were alive as of 15.4 months.
Regarding toxicity, 95 percent of patients experienced at least one side effect that was severe. The most common adverse events of grade III or higher during treatment were neutropenia (in 78 percent of patients), anemia (in 43 percent), and thrombocytopenia (in 38 percent).
Grade III or higher cytokine release syndrome (released because of overstimulation of the immune system with CAR T-cells expanding) and neurologic events occurred in 13 percent and 28 percent of the patients, respectively. The use of low dose steroids and/or monoclonal antibody anti-IL6 receptor (to block one of the commonly found elevated cytokines IL6), tocilizumab, has dramatically helped manage toxicities.
Ongoing studies are looking at improving both toxicities and efficacy of CAR T-cell therapy using combinations particularly with checkpoint inhibitors.
Hackensack Meridian Health – John Theurer Cancer Center at Hackensack University Medical Center is the only New Jersey center that participated in a pivotal clinical trial of a groundbreaking cancer treatment, CAR-T cell therapy, which genetically modifies a patient’s immune system to attack cancer cells.
André Goy, chairman and director, chief of lymphoma, and director of clinical and translational cancer research at John Theurer Cancer Center, is a co-author of the study, presented at the 59th Annual Meeting of the American Society of Hematology in the New England Journal of Medicine.
