It was reported that a patient with heavily pretreated relapsed/refractory diffuse large B-cell lymphoma (DLBCL), a notoriously aggressive blood cancer, achieved complete remission following one month of treatment with a novel in vivo CD19 CAR-T therapy, showing durable response sustained over three months’ time.
These clinical data were shared in a news release from Genocury Biotech and obtained during an investigator-initiated trial led at Tongji Hospital, in China. The Company went on to note that this specific line of treatment also eliminated the need for lymphodepletion which is a standard yet toxic preconditioning step in traditional CAR-T protocols. The CD19 CAR-T therapy went on to demonstrate safety, efficiency and durability.
“In this groundbreaking case, we observed the patient treated with Genocury's CD19 in vivo CAR-T achieved complete remission through 90-day follow-up,” Dr. Jia Wei, principal investigator of the trial, stated in the news release. “[This was] achieved without any lymphodepletion, which fundamentally challenges current cellular therapy dogma. This therapy combines the benefits of autologous CAR-T with the accessibility of universal therapies, potentially ending the era of unaffordable cancer treatments. This could democratize access to CAR-T globally, we are very excited to advance this paradigm-shifting approach.”
Wei currently works as a professor in the Department of Hematology, at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, located in Wuhan, China.
Regarding the (male) patient with relapsed DLBCL who experienced a rapid and deep response, he achieved a complete hematological remission within 28 days of treatment following a single dose of the CD19 in vivo CAR-T without lymphodepletion. Moreover, sustained therapeutic efficacy was observed during the 90-day follow-up period following the flow cytometric analysis, which revealed robust expansion kinetics of CAR-T cells.
Glossary:
Lymphodepletion: a short course of chemotherapy to kill T cells, a part of the immune system, prior to treatment with CAR-T cell therapy.
Complete hematological remission: when your disease is gone, and blood counts have fully recovered.
Cytokine release syndrome: when your immune system responds to infection or immunotherapy drugs more aggressively than it should.
Immune effector cell-associated neurotoxicity syndrome: clinical and neuropsychiatric syndrome that can occur in the days to weeks following administration of certain types of immunotherapies.
Looking to the safety of the investigational therapy, this novel therapeutic approach demonstrated complete absence of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome and lymphodepletion-related complications (these complications are associated with an increased infection risk). This stands in contrast to some conventional CAR-T therapies, which carry an approximate 50% risk of cytokine release syndrome and neurotoxicity.
More Information on the Investigational Therapy and CAR-T Cell Therapy
CAR-T cell therapy, according to the American Cancer Society's website, cancer.org, is used to find and destroy cancer cells with T cells (immune cells; a type of white blood cell) by changing the T cells in the lab. In this process, patients will remain in an inpatient medical facility where healthcare professionals will take T cells are from the patient's blood and change them by adding a gene for a receptor called a chimeric antigen receptor (CAR); this helps the cells attach to a specific cancer cell antigen. Finally, these now-modified CAR T cells are then given back to the patient.
Although, according to the website, even when other treatments are no longer working, CAR-T can be very helpful, there remains some unmet needs within the treatment space. However, the investigational CAR-T platform aims to overcome two major roadblocks in current CAR-T therapy, according to the news release.
Firstly, the investigational therapy eliminates ex vivo manipulation. For example, traditional CAR-T harvests, modifies and expands a patient's T cells outside the body, requiring a three-to-four-week vein-to-vein timeline, as well as a nearly $400,000 cost for the time-consuming process. In comparison, the proprietary in vivo CAR-T delivers the CAR directly into circulating T cells in vivo, which in turn, enables functional CAR-T generation.
Additionally, with a lymphodepletion-free approach, the investigational CAR-T product reduces treatment-related complications and logistical burdens whereas current therapies require lymphodepletion, a harsh preconditioning chemotherapy for immune reset.
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