January 10, 2020
First study of CAR T-cell immunotherapy in recurrent/persistent MCL showing a 93% objective response rate and 67% complete response rate in patients with no other options
Investigators at John Theurer Cancer Center (JTCC) at Hackensack University Medical Center in New Jersey were part of the 15-site international ZUMA-2 trial, a phase II study of CAR T-cell therapy in a heavily pretreated patient population who had exhausted all standard treatment options for mantle cell lymphoma (MCL).
After a single infusion of KTE-X19, 93% of patients with relapsed/refractory MCL responded and 67% achieved a complete response (CR) rate (i.e., no remaining disease). These unprecedented results were presented at the 2019 American Society of Hematology (ASH) Annual Meeting, held in December in Orlando, Florida — the world’s leading conference for hematologic cancers and blood disorders.
With CAR T-cell therapy, white blood cells called T cells are removed from the patient, modified in the laboratory to make them recognize a protein (CD19) on lymphoma cells, then expanded to much larger numbers and returned to the patient intravenously, where they can expand further to detect and destroy cancer cells anywhere in the body. Two forms of CAR T-cell therapy — aci-cell (Yescarta®) and tisa-cell (Kymriah®) — are currently approved by the U.S. Food and Drug Administration to treat recurrent and persistent B-cell lymphoma in adults, as well as acute lymphoblastic leukemia in children and young adults up to age 25. However, CAR T-cell therapy is not yet approved to treat MCL, an aggressive type of non-Hodgkin lymphoma which becomes resistant to therapy over time and is associated with very poor outcomes.
The ZUMA-2 study included MCL patients who had failed to respond to both chemoimmunotherapy and BTK inhibitors, such as ibrutinib or acalabrutinib. The 93% response rate and 67% CR rate were observed regardless of the number of prior therapies or extent of disease. Interestingly, 40% of patients who initially had a partial response or stable disease achieved a CR within 3 to 12 months, showing the effectiveness of a “living drug” that continues to work over time.
Responses were also durable, with one-year estimates of progression-free survival (the time before the cancer continued to grow) and overall survival being 71% and 86%, respectively. At the time of analysis, the median duration of response had not yet been reached, and for those who achieved a CR, 78% of patients remained in remission. For the first 28 patients who were treated with axi-cel and had the longest follow-up time (median 27 months), 43% of the responders remained in remission — a rate totally unprecedented for this population.
“This will be a true game-changer in the management of patients with mantle cell lymphoma,” said Andre Goy, M.D., M.S., Chairman and Director of JTCC, Lymphoma Division Chief, and a renowned lymphoma expert who led JTCC’s participation in the ZUMA-2 study.
Side effects were generally manageable and as expected with CAR T-cell therapy, including low blood cell counts, cytokine release syndrome (a release of inflammatory proteins associated with the immune response), and nervous system side effects that were all reversible.
About John Theurer Cancer Center at Hackensack University Medical Center
John Theurer Cancer Center at Hackensack University Medical Center is New Jersey’s largest and most comprehensive center dedicated to the diagnosis, treatment, management, research, screenings, and preventive care as well as survivorship of patients with all types of cancers. The 15 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. John Theurer Cancer Center is a member of the Georgetown Lombardi Comprehensive Cancer Center Consortium, one of just 16 NCI-approved cancer research consortia based at the nation’s most prestigious institutions. Housed within a 775-bed not-for-profit teaching, tertiary care, and research hospital, John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of aftercare services that distinguish John Theurer Cancer Center from other facilities. For additional information, please visit http://www.jtcancercenter.org.
SOURCE John Theurer Cancer Center