FDA Approves Yescarta, First CAR-T Cell Therapy, for Patients With Large B-Cell Lymphoma That Has Failed Initial Treatment

The FDA’s decision to approve Yescarta in patients with large B-cell lymphoma that has failed to respond to first-line treatment is based on data that showed that the use of the CAR-T cell therapy resulted in a significant increase in patients who were alive at two years compared with the standard-of-care second-line treatment.

The Food and Drug Administration (FDA) recently approved Yescarta (axicabtagene ciloleucel) for use in adults with large B-cell lymphoma that has failed to respond to initial treatment with chemoimmunotherapy or that has returned within one year of said treatment, according to the agent’s manufacturer, Kite Pharma.

The approval, according to the news release, marks the first CAR-T cell therapy for this patient population.

“(This) approval marks an exciting new standard of care,” Dr. Frederick L. Locke, co-leader of the Immuno-Oncology Program at Moffitt Cancer Center in Tampa, Florida, said in the release. “What we found was that (Yescarta) resulted in three times as many patients receiving treatment with curative intent (CAR-T cell therapy), and an overall better outcome for patients than the previous standard of care. Additionally, we have now amassed significant experience with CAR-T cell therapy to better manage or prevent side effects, making this treatment more accessible for older patients and those with medical conditions for whom the standard of care might be difficult.”

The typical standard of care, as the release noted, has been the initial use of chemoimmunotherapy followed by high-dose chemotherapy if the disease responded to and tolerated the primary treatment. If patients can receive both regimens, they then are given an autologous stem cell transplant.

The FDA based its decision to approve Yescarta using data from the global, phase 3 ZUMA-7 trial, which demonstrated that treatment with Yescarta resulted in a 2.5-fold increase in patients who were alive at two years and did not experience cancer progression or require the need for additional cancer treatment (40.5% versus 16.3%) and a four-fold greater median event-free survival (time from randomization to the earliest date of disease progression; 8.3 months versus two months) compared with the second-line standard of care.

Moreover, 94% of the patients who were treated with Yescarta were able to receive a stem cell transplant compared with 35% of those who were administered second-line standard of care.

The overall response rate, or percentage of patients whose disease partially or completely responded to treatment, also favored those in the Yescarta group (83% versus 50%).

Side effects from Yescarta observed in ZUMA-7 were similar to those that were previously noted for Yescarta use. Severe (grade 3 or higher) cytokine release syndrome (a condition where the body releases too many inflammatory molecules called cytokines) were observed in 7% of patients, while neurotoxicity was seen in 25%. In the group of patients receiving standard of care, 83% had high-grade events, mostly consisting of low blood counts.

“Definitive clinical trial results such as these do not come along often and should drive a paradigm shift in how patients with relapsed or refractory (large B-cell lymphoma) are treated moving forward,” Dr. Jason Westin, director of Lymphoma Clinical Research at The University of Texas MD Anderson Cancer Center in Houston, said in the release. “Patients who do not respond to or relapse after initial treatment should quickly be referred to a CAR-T cell therapy-authorized treatment center for evaluation.”

The FDA previously approved Yescarta in 2017 for the treatment of patients with large B-cell lymphoma whose disease progressed on multiple lines of therapy.

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