August 04, 2021

By Kristi Birch

Axicabtagene ciloleucel, known by its brand name, Yescarta, is 60% more effective than the current standard of care in treating people with large B-cell lymphoma (LBCL) who did not respond well to, or relapsed after, the first line of treatment, according to early results of a global Phase 3 clinical trial.

Yescarta was first approved by the U.S. Food and Drug Administration in 2017 as a third-line treatment for adults with LBCL, i.e., for those who had already undergone two rounds of treatment that failed. The ZUMA-7 trial sought to determine if Yescarta is superior to the existing, longstanding second-line standard of care, which is a stem cell transplant following high-dose chemotherapy to kill the lymphoma.

"This is a paradigm shift," said Joseph McGuirk, D.O., medical director of the blood and marrow transplant program at The University of Kansas Cancer Center, which is one of the leading sites in enrolling participants in the trial. "We're seeing upfront responses that are significantly better than what we see with autologous stem cell transplants."

Made by Kite Pharma, Yescarta is a form of CAR-T therapy. With this novel type of immunotherapy, blood is drawn from a patient, T-cells (white blood cells that detect disease-causing organisms in the body) are extracted and genetically re-engineered. These turbocharged cells are used to create the drug that is injected back into the patient to attack cancer.

About 40% of people with LBCL need second-line treatment, either because their cancer returns or does not respond adequately to frontline treatment.

ZUMA-7 began in 2017 and enrolled 359 people in 77 trial sites around the world. Participants ranged in age from 22 to 81. Nearly one-third of them were 65 and older, an age that in some countries would render them ineligible for a stem cell transplant.

The study evaluated a one-time infusion of Yescarta compared with standard of care in patients who had relapsed or had refractory LBCL after frontline treatment. The randomized trial measured "event-free survival," defined as survival without disease progression, the beginning of a new lymphoma therapy or death from any cause. The median follow-up time was two years, the longest follow-up of any second-line trial.

The early results show that, compared with the standard regimen of chemotherapy and a stem cell transplant), Yescarta improved event-free survival by 60%. Moreover, the safety results were as good or better than they are for existing third-line Yescarta treatment.

The study also measured complete and partial responses to treatment. Preliminary analysis suggests a trend favoring Yescarta, but these data need further analysis before they are released.

"I believe we are likely to see the field quickly move away from autologous stem cell transplant toward CAR-T cell therapy as a second-line therapy for relapsed or refractory diffuse large B-cell lymphoma," said McGuirk.

Last modified: Aug 04, 2021