CAR T-Cell Therapy for Lymphoma Leads to Complete Remission in Phase I Trial

An engineered CAR T cell (center) binding to beads, which causes the T cell to divide. In CAR T-cell therapy, the engineered T cells are expanded into the hundreds of millions and then infused back into the patient. [NIH]

Immunotherapy approaches for treating cancer continue to exceed expectations by providing novel, highly efficient treatment options. Adding another potential success to the immunotherapy toolbox, investigators from the Moffitt Cancer Center just released promising results from the Phase I portion of the ZUMA-1 study, which uses chimeric antigen receptor (CAR)-modified T cells to treat B-cell lymphoma patients.

Lymphoma is the most common blood cancer, with the disease occurring when lymphocytes multiply uncontrollably. Cancerous lymphocytes can travel throughout the body and form lymph node tumors. The body has two types of lymphocytes that can develop into lymphoma—B cells and T cells. B-cell lymphomas account for 85% of all non-Hodgkin lymphomas, and 30% of those patients are diagnosed with diffuse large B-cell lymphoma.     

Diffuse large B-cell lymphoma is an aggressive B-cell cancer that can spread quickly throughout the body—requiring immediate treatment, including drug therapy, radiation therapy, and possibly a stem cell transplant. However, half of all diffuse large B-cell patients relapse after standard therapies and become unresponsive to chemotherapy treatments (refractory disease).

Diagram of how CAR T cells are generated. [Lymphomation.org]

The Phase I trial results were centered around the use of axicabtagene ciloleucel (KTE-C19), developed by Kite Pharma, an autologous CAR T-cell therapy. In this study, T cells were isolated from a patient's blood and engineered to target the CD19 protein that is found on lymphoma cells. The retargeted T cells were then infused back into the same patient. KTE-C19 T cells were able to recognize cancerous lymphoma cells that express CD19 and target them for destruction.  

The goal of this portion of the ZUMA-1 study was to determine the safety of KTE-C19, as assessed by the frequency of dose-limiting toxicities in patients with diffuse large B-cell lymphoma who were refractory to prior therapy—which included anti-CD20 therapy and an anthracycline-containing regimen. The study included patients who had highly refractory disease, with two to four prior treatments.

The Moffit researchers found that KTE-C19 caused expected, but manageable, toxicity over a median follow-up period of 9 months. Of the seven patients treated with KTE-C19, one patient experienced dose-limiting toxicity of cytokine release syndrome and neurotoxicity. Yet, KTE-C19 produced promising clinical activity. The overall response rate was 71% (5 of 7 patients), and 4 patients developed a rapid, complete response within 1 month of treatment. The treatment was also durable with 43%, or 3 patients remaining in full remission after 1 year.

“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% with conventional chemotherapies,” noted lead study investigator Frederick Locke, M.D., director of research for Moffitt's Immune Cell Therapy Clinical Trial Group. “This is truly an exciting time for the oncology community and our patients. Engineered immune cell therapies are one step closer to widespread availability.”

The promising Phase I results led to the initiation of the pivotal Phase II portion of the ZUMA-1 study in aggressive non-Hodgkin lymphoma, which includes diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma.