Yescarta (axicabtagene ciloleucel, formerly KTE-C19) is a therapy developed by Kite Pharma for people with aggressive B-cell non-Hodgkin’s Lymphoma (NHL) who have exhausted other treatment options. It is a type of chimeric antigen receptor (CAR) T-cell therapy, which manipulates the patient’s own T-cells to recognize and destroy cancer cells.
Yescarta was approved by the U.S. Food and Drug Administration (FDA) on Oct. 18, 2017.
How Yescarta works
Yescarta consists of a patient’s own T-cells that have been modified in the laboratory. To make Yescarta, T-cells are first harvested from the patient and then altered to express a CAR surface protein directed against CD19. CD19 is a protein found on the surface of B-cells in many different types of lymphomas and leukemias. When the Yescarta CAR T-cells are infused back into the patient’s body, the T-cells are able to recognize and kill CD19-expressing cancerous B-cells.
Yescarta in clinical trials
Five single-arm, multicenter clinical trials — ZUMA-1, ZUMA-2, ZUMA-3, ZUMA-4, and ZUMA-5 — tested KTE-C19 in people with aggressive B-cell lymphomas or leukemias who have been treated with chemotherapy but either did not achieve remission (refractory cancer) or had the cancer return after remission (relapsing cancer).
Yescarta’s approval was supported by data from ZUMA-1 (NCT02348216), a Phase 1/2 study that began in January 2015. For the trial, patients with NHL were divided into two treatment groups based on their NHL subtype. One group of 73 patients had diffuse large B-cell lymphoma (DLBCL) and the other group of 20 patients either had primary mediastinal B-cell lymphoma (PMBCL) or transformed follicular lymphoma (TFL). All patients in the study received a three-day course of chemotherapy followed by one single infusion of Yescarta.
Early results from the ZUMA-1 trial showed an overall response rate (ORR) of 71% in the first seven patients treated with Yescarta. In June 2017, the European Hematology Association reported a response rate of 82% based on data from 101 patients at a median follow-up of 8.7 months, with 39% in complete remission. The response was similar across disease subtypes, prognosis, and cancer stage.
The most common adverse effects seen in ZUMA-1 were lower blood cell counts. More serious adverse events included cytokine release syndrome (CRS) and brain swelling, which caused one death. The safety profile is considered acceptable because the patients have an aggressive disease with no other treatment options.
ZUMA-2 (NCT02601313) is a Phase 2 study of Yescarta in patients with refractory or relapsing mantle cell lymphoma, another subtype of NHL. ZUMA-3 (NCT02614066) is a Phase 1/2 study of Yescarta in adult patients with refractory or relapsing acute lymphoblastic leukemia (ALL).
In June 2017, Kite reported that 73% of patients in the Phase 1 portion of the ZUMA-3 trial achieved complete remission following an updated analysis of study data, which included 11 patients treated with Yescarta at two different target doses.
ZUMA-4 (NCT02625480), a Phase 1/2 study that began in December 2015, will include roughly 75 children and adolescents ages 2-21 who have a form of ALL. ZUMA-5 (NCT03105336), a Phase 2 study, began in May 2017 and enrolled its first patient in August the same year. It will include about 50 adults with either follicular lymphoma, marginal zone lymphoma, or indolent NHL.
Finally, ZUMA-9 (NCT03153462), an expanded access study, will allow patients who could not enroll in previous ZUMA trials to access Yescarta. All of the ZUMA trials mentioned above are still recruiting participants at different sites across the world.
Most common side effects of Yescarta include fever, low white and red blood cell counts, low blood pressure, dizziness or lightheadedness, headache, tiredness, shortness of breath, fast heartbeat, confusion, difficulty speaking or slurred speech, nausea, and diarrhea.
Yescarta should not be administered to patients with active infections or inflammatory diseases due to the risk of fatal or life-threatening neurological reactions or CRS. CRS is a response by the body to the activation and growth of CAR-T cells, which causes high fever and flu-like symptoms.
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