The Food and Drug Administration (FDA) has granted accelerated approval to Yescarta® (axicabtagene ciloleucel; Kite Pharma) for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after 2 or more lines of systemic therapy.
The approval was based on data from the single-arm, open-label phase 2 ZUMA-5 study (ClinicalTrials.gov: NCT03105336), which evaluated Yescarta, a CD19-directed genetically modified autologous T cell immunotherapy, in 146 patients 18 years of age and older with relapsed or refractory indolent non-Hodgkin lymphoma who received at least 2 prior lines of systemic therapy. The primary end point was the objective response rate (ORR); a key secondary end point included the duration of response (DoR).
Among follicular lymphoma patients who were evaluable for efficacy analysis (n=81), results showed an ORR of 91% after a single intravenous infusion of Yescarta; an estimated 74% of patients were reported to be in continued remission at 18 months (Kaplan-Meier estimate). Moreover, 13 of the 25 patients who achieved a partial remission met imaging criteria for complete remission without confirmation by negative bone marrow biopsy after treatment. The median DoR was not reached yet at a median follow-up of 14.5 months.
Among the 146 patients evaluable for safety, the incidence of grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities was 8% and 21%, respectively, with a median time to onset of 4 days (range, 1-20 days) and 6 days (range, 1-79 days), respectively. The most common (incidence of greater than or equal to 10%) grade 3 or higher adverse reactions included febrile neutropenia, encephalopathy, and infections with an unspecified pathogen.
Yescarta carries a Boxed Warning regarding CRS and neurologic toxicities. Due to these potentially life-threatening reactions, the treatment is only available through a restricted program called the Yescarta and Tecartus REMS program.
Commenting on the approval, Christi Shaw, Chief Executive Officer of Kite, said: “Advancing CAR T therapies for patients across lymphomas remains a cornerstone of our cell therapy development program, and we are excited about the potential of Yescarta for patients with indolent follicular lymphoma.”
Yescarta is also indicated for the treatment of adults with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
The product is available as a cell suspension for infusion containing 2×106 CAR-positive viable T cells per kg of body weight, with a maximum of 2×108 CAR-positive viable T cells in approximately 68mL.
1. U.S. FDA approves Yescarta® for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. [press release]. Santa Monica, CA: Kite Pharma; March 5, 2021.
2. Yescarta [package insert]. Santa Monica, CA: Kite Pharma; 2021.