Kite Pharma Updates Results of CAR-T cell therapy in Aggressive Non-Hodgkin Lymphoma

Results from the ZUMA-1 trial of axicabtagene ciloleucel (KTE-C19) in patients with chemorefractory aggressive non-Hodgkin lymphoma (NHL) were updated recently at the American Society of Hematology Annual Meeting in San Diego, California.  Overall 76% of patients with Diffuse Large B-Cell Lymphoma (DLBCL) responded to treatment, 47% achieving a complete remissions (CR).

About axicabtagene ciloleucel

Axicabtagene ciloleucel, is an investigational therapy in which a patient’s T cells are engineered to express a chimeric antigen receptor (CAR) to target the antigen CD19, a protein expressed on the cell surface of B-cell lymphomas and leukemias, and redirect the T cells to kill cancer cells.

About CAR-T

CAR-T, or chimeric antigen receptor T-cells, is a new form of cancer immunotherapy in which a patient’s own T cells are removed and then engineered to identify and kill malignant blood cancer cells. The use of a patient’s own immune cells to fight cancer is proving to be a promising therapeutic approach in the treatment of some lymphomas.

One characteristic of a cancer cell is its ability to evade an attack by a person’s immune system. Immune cells are constantly surveying the body for potential threats, such as a bacteria or virus. Once the immune system detects such a threat, it initiates an attack against it.

Historically, researchers have remained perplexed as to how cancer cells remain undetected as a threat by the immune system. However, research has recently unraveled some of the mechanisms used by cancer cells to evade immune detection. Furthermore, researchers have also learned ways to stimulate the immune system to effectively recognize cancer cells.

One method of stimulating the immune system to detect cancer cells is referred to as chimeric antigen receptor T cell (CAR-T) therapy. Using this type of treatment, researchers take a sample of blood from the patient, and collect certain immune cells called T-cells.

Through laboratory processes, the collected T-cells are reprogrammed to recognize and attack the patient’s cancer cells. Once the T-cells multiply and reach a certain number in the laboratory (usually hundreds of millions to billions), they are re-infused into the patient. The infused T-cells then circulate throughout the body, attacking the patient’s cancer cells.

The ZUMA-1 clinical trial enrolled 111 patients with chemo-refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma. Chemo-refractory disease was defined as progressive or stable disease as best response to last line of therapy, or disease progression ≤12 months after autologous stem cell transplant.

Manufacturing was successful for 110 patients, and 101 patients were treated. Responses were observed across key subgroups, including 75 percent CR in patients who relapsed in ≤12 months after autologous stem cell transplant and 47 percent CR in patients refractory to second line or later chemotherapy.

The most common significant side effects included neutropenia (63%), anemia (42%), febrile neutropenia (29%), and thrombocytopenia (26%).  Three patients died while undergoing treatment.

Reference: Feuerstein, Adam. Kite Pharma Claims CAT-T Trial Victory, FDA Filing Next. The Street. Can be accessed at https://www.thestreet.com/story/13752310/1/kite-pharma-claims-car-t-trial-victory-fda-filing-next.html

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