ZUMA-7 Results Underscore Yescarta's Efficacy for LBCL

According to results of a primary analysis of ZUMA-7—a randomized phase 3 multicenter study—axicabtagene ciloleucel (Yescarta) improved event-free survival (EFS; HR, 0.398; P <.0001) by 60% over chemotherapy and stem cell transplant among patients with second-line relapsed or refractory large B-cell lymphoma (LBCL).

The study was initiated in 2017 as the first randomized clinical trial to test earlier use of a chimeric antigen receptor T-cell therapy against standard of care (SOC) and had a median follow-up time of 2 years—the longest of any study in this setting. A total of 359 patients aged 22 to 81 years were initially enrolled in 77 centers around the world. Over 30% of participants were aged 65 or older. Results show the study met its primary end point of EFS and its secondary end point of objective response rate.

Interim analyses also revealed an overall survival trend favoring Yescarta, but further analyses are warranted as data were immature. More detailed results are slated to be presented at a future medical congress, while Kite, a Gilead company, plans to initiate discussions with regulators regarding a submission for a supplemental biologics license application to expand the treatment’s currently approved indications.

The trial was also conducted under a Special Protocol Agreement (SPA) with the FDA, meaning its design, clinical end points, and statistical analysis were all agreed upon in advance with the agency.

Adult participants received a one-time infusion of Yescarta and outcomes were compared with those who received SOC treatment, defined as a reintroduction of immunochemotherapy. If the patient responded and could tolerate more treatment, they then received a high-dose chemotherapy and stem cell treatment.

“The top-line results of the randomized ZUMA-7 trial paint the picture of a potential paradigm shift in the treatment of large B-cell lymphoma,” said Frederick L. Locke, MD, the trial’s lead investigator and coleader of the Immuno-Oncology Program at Moffitt Cancer Center in Tampa, Florida.

“The outcomes for patients relapsing after frontline chemotherapy in this study are dramatically improved with rapid referral (to a CAR T center) and a single infusion of axicabtagene ciloleucel as compared to chemotherapy and consolidative autologous transplant, the longstanding second-line standard of care,” he said.

Safety results were consistent with or lower than the treatment’s known safety profile when administered in the third-line setting. Specifically, the researchers found:

• 6% of patients experienced grade 3 or higher cytokine release syndrome (CRS), with a median onset of 3 days
• 21% of patients experienced grade 3 or higher neurological events
• No new safety concerns were identified in this second-line setting

Yescarta is currently not approved by any agency to treat patients in the second-line setting, although around 40% of patients with LBCL will need second-line treatment because their cancer will relapse or become refractory.

In addition, the treatment is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) and is indicated for adult patients with relapsed or refractory LBCL after 2 or more lines of systemic therapy and those with relapsed or refractory follicular lymphoma after 2 or more lines of systemic therapy.

The REMS program mandates “health care facilities that dispense and administer Yescarta must be enrolled and comply with the REMS requirements and must have on-site, immediate access to a minimum of 2 doses of tocilizumab for each patient for infusion within 2 hours after Yescarta infusion, if needed for treatment of CRS.”

Reference

Kite announces Yescarta CAR T-cell therapy improved event-free survival by 60% over chemotherapy plus stem cell transplant in second-line relapsed or refractory large B-cell lymphoma. Press release. Gilead; June 28, 2021. Accessed July 1, 2021. https://investors.gilead.com/news-releases/news-release-details/kite-announces-yescartar-car-t-cell-therapy-improved-event-free