Successful Chimeric Antigen Receptor–Expressing T-Cell Treatment Reported in Advanced Lymphomas
Development of autologous genetically engineered anti-CD19 chimeric antigen receptor (CAR)-expressing T cells holds promise in the treatment of hematologic malignancies. CAR T cells are being studied in adult and pediatric acute lymphocytic leukemias and in chronic lymphocytic leukemia, and dramatic responses have been shown in patients with advanced disease who have run out of options. A new study reported today at the 55th American Society of Hematology (ASH) Annual Meeting and Exposition describes the first evidence of the use of CAR T cells in advanced aggressive lymphomas, and preliminary results appear to be as promising as they are in leukemia (Abstract 168).
Study Details
This study reports successful treatment with CAR T cells in a total of 15 patients with chemorefractory B-cell lymphomas. Nine patients had aggressive large B-cell lymphomas and six had a variety of indolent B-cell lymphomas. Patients’ ages ranged from 30 to 68 years.
“Our data provide the first true glimpse of the potential of this approach in patients with aggressive lymphomas that, until this point, were virtually untreatable and have a very poor prognosis. The novel finding is that CAR T cells can eradicate solid tumor mass,” said lead author James N. Kochenderfer, MD, an investigator in the Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, Maryland.
Patients underwent a conditioning regimen with cyclophosphamide and fludarabine prior to receiving a single infusion of their own genetically modified T cells. This conditioning regimen was used because prior chemotherapy has been shown to enhance the activity of CAR T cells in patients.
Outcomes
Seven patients achieved complete response and five achieved partial response. One patient died of cardiac arrhythmias and a second patient was lost to follow-up. Acute toxicities included fever, low blood pressure, focal neurologic deficits, and delirium. These toxicities resolved in less than 3 weeks.
“We are particularly encouraged by the partial and complete responses that we observed in a number of patients with diffuse large B-cell lymphomas who had exhausted all other treatment options. This approach offers an option for patients with chemotherapy-refractory large B-cell lymphomas who are not generally thought to be good candidates for hematopoietic stem cell transplantation.”
Investigators at several institutions are studying CAR T cells in hematologic malignancies, and the protocols vary depending on the institution. In the protocol used in the current study, the CAR is encoded by a gammaretrovirus and incorporates regions of an anti-CD19 antibody, part of CD28, and part of CD3-zeta. The CAR T-cell protocols are evolving and are still in early stages.
“We will continue our research to improve further the protocol and evaluate its value in additional patients with treatment-resistant disease,” Dr. Kochenderfer said.
The study was funded by Kite Pharma.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
