What you need to know
Investigators at John Theurer Cancer Center (JTCC) at Hackensack University Medical Center 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.
More details about CAR T-Cell Therapy
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.
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.