Promising results from the phase 1 portion of the ZUMA-1
study, which uses chimeric antigen receptor (CAR) modified T cells to
treat b-cell lymphoma patients, were published in the January issue of Molecular Therapy, the official journal of the American Society of Gene and Cell Therapy.
Lymphoma, the most common blood cancer, occurs when
immune cells called lymphocytes multiply uncontrollably. Cancerous
lymphocytes can travel throughout the body and form lymph node tumors.
‘Results from phase I trial using chimeric antigen receptor (CAR) T-cell therapy with axicabtagene ciloleucel (KTE-C19) show durable complete remission in highly refractory diffuse large B-cell lymphoma patients.’
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 quickly spread throughout the body. This means it requires 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).
Moffitt Cancer Center physician investigators are working to bring
immune cellular therapies to refractory diffuse large B-cell lymphoma
Axicabtagene ciloleucel (KTE-C19), developed by Kite Pharma, is an
autologous chimeric antigen receptor (CAR) T-cell therapy. In CAR-T
therapy using axicabtagene ciloleucel (KTE-C19), T cells are isolated
from a patient's blood and engineered in Kite Pharma's central
manufacturing facility to target the CD19 protein that is found on
The re-targeted T cells are then infused back into the
same patient. Axicabtagene ciloleucel (KTE-C19) T cells are able to
recognize cancerous lymphoma cells that express CD19 and target them for
The goal of the phase 1 portion of the ZUMA-1 study was to determine
the safety of axicabtagene ciloleucel (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 that included
anti-CD20 therapy and an anthracycline-containing regimen. The study
included patients who had highly refractory disease, with two to four
This is the first multicenter study of a CAR-T therapy that was
produced manufactured at a centrally located facility. The Moffitt
research team, led by Frederick L. Locke, reports that the
manufacturing process for axicabtagene ciloleucel (KTE-C19) was
successful for all of the patients and was completed within
approximately two weeks.
After the successful manufacturing of axicabtagene ciloleucel
(KTE-C19), cells were shipped back to Moffitt and the other
participating sites where patients were treated with conditioning
chemotherapy followed by infusion with axicabtagene ciloleucel
(KTE-C19). Locke's team found that axicabtagene ciloleucel (KTE-C19)
caused expected, but manageable, toxicity over a median follow-up period
of nine months. Of the seven patients treated with axicabtagene ciloleucel
(KTE-C19), one patient experienced dose-limiting toxicity of cytokine
release syndrome and neurotoxicity.
Axicabtagene ciloleucel (KTE-C19) resulted in promising clinical
activity. The overall response rate was 71% (five of seven patients)
and four patients developed a rapid complete response within one month of
treatment. The treatment was also durable with 43%, or three patients
remaining in complete remission after one 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. This is truly an
exciting time for the oncology community and our patients. Engineered
immune cell therapies are one step closer to widespread availability."
said Locke, Director of Research for Moffitt's Immune Cell Therapy
Clinical Trial Group.
The promising phase 1 results led to the initiation of the pivotal
phase 2 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.