Patients with refractory diffuse large B-cell lymphoma (DLBCL) could greatly benefit from a new CAR T-cell therapy called KTE-C19, according to recently published data from the Phase 1 ZUMA-1 trial.
KTE-C19 uses T-cells, isolated from the patient’s blood, that are genetically engineered in a lab to recognize the CD19 protein — found at the surface of most lymphoma cells. The engineered cells are then expanded to generate millions of tumor-killing T-cells and are infused back into the patient.
The trial (NCT02348216) was a multicenter, single-arm, open-label study designed to assess KTE-C19’s safety and efficacy in DLBCL patients with highly refractory disease who had received two to four treatments, including an anti-CD20 therapy and an anthracycline-based treatment.
The study, “Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma,” published in Molecular Therapy, reveals that 71% of patients treated with KTE-C19 responded to the therapy. The complete response rate was 57% — meaning that for those patients, evidence showed that the cancer was gone. That percentage largely exceeds the 8% complete response rate for patients who undergo standard therapies.
After a median followup of nine months, the trial showed that KTE-C19 caused expected, but manageable, toxicity, with only one of the seven DLBCL-treated patients exhibiting dose-limiting toxicity from excessive immune activation and neurotoxicity.
The response to treatment was found to be long term — three of the four patients who achieved complete response were still in complete remission a year after treatment. And CAR T-cells were still detected in the patients’ blood more than 12 months after treatment.
“The overall and complete response rate in this small group of patients is remarkable, as the expected complete response rate for such patients is 8 percent with conventional chemotherapies. This is truly an exciting time for the oncology community and our patients. Engineered immune cell therapies are one step closer to widespread availability,” Frederick L. Locke, MD, director of Research for the Moffitt Cancer Center Immune Cell Therapy Clinical Trial Group, said in a news release.
This is the first multicenter study of a CAR T-cell therapy in which the engineered cells were manufactured in a centralized, closed process. The researchers said the manufacturing process was successful for all the patients and was completed within eight days.
Based on these positive results, the Moffitt team has initiated the Phase 2 portion of the ZUMA-1 trial in patients with aggressive non-Hodgkin lymphoma. That trial, also identified as NCT02348216, is recruiting patients.
Diffuse large B-cell lymphoma is an aggressive B-cell cancer that is often treated with drug therapy, radiation, and if possible, a stem cell transplant. However, nearly half of patients with DLBCL relapse after standard therapies and stop responding to chemotherapy.