ZUMA-7 Trial Meets Event-Free Survival End Point in Large B-Cell Lymphoma

The ZUMA-7 trial (NCT03391466) demonstrated superiority of axicabtagene ciloleucel (axi-cel; Yescarta) compared with standard of care (SOC) autologous stem cell transplant (ASCT) after meeting the primary end point of event-free survival (EFS) improvement for patients with relapsed or refractory large B-cell lymphoma (LBCL), according to a press release from the company responsible for manufacturing the chimeric antigen receptor (CAR) T-cell therapy, Kite, A Gilead Company.

A statistically significant EFS benefit (HR, 0.398; P <0.0001) was observed as well as improvement in the secondary end point of objective response rate (ORR).

“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,” Frederick L. Locke, MD, ZUMA-7 lead principal investigator and co-leader of the Immuno-Oncology Program at Moffitt Cancer Center in Tampa, Florida, said in a press release. “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.”

This trial looked at a 1-time infusion of axi-cel treatment consisting of an intravenous infusion of CAR-T cells following a conditioning chemotherapy regimen of fludarabine and cyclophosphamide vs platinum-based immunochemotherapy followed by high-dose therapy and ASCT, the SOC for relapsed or refractory LBCL.

The ZUMA-7 is an open-label phase 3 trial of 359 patients across 77 centers around the world who were randomization in a 1:1 fashion to the experimental or control therapy arms.

Inclusion criteria were histologically proven LBCL, relapsed or refractory disease after first-line chemotherapy, and prior receipt of adequate first-line therapy. Exclusion criteria were the presence of any malignancy other than nonmelanoma skin cancer or carcinoma in situr, prior receipt of more than 1 line of therapy, and a history of stem cell transplant. 2

Safety was consistent with the known safety profile of axi-cel in the third-line setting, with grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurring in 6% and 21%, respectively. The most common adverse effects occurring in 20% of patients or more included hypotension, encephalopathy, tachycardia, fatigue, headache, and decreased appetite among others. 

Of note, investigators mention that these data are still immature and further analyses are planned for the future. The trial was conducted under a Special Protocol Agreement from the FDA where the trial design, end points, and statistical analysis were agreed in advance.

“Yescarta has been instrumental in transforming outcomes for patients with third-line LBCL. Our goal has always been to bring the benefit of CAR T-cell therapy to more patients, earlier in their treatment, where the potential for benefit may be even greater,” Christi Shaw, chief executive officer of Kite, said in a press release.

Reference

Kite Announces Yescarta Car T-Cell Therapy Improved Event-Free Survivial by 60% Over Chemotherapy Plus Stem Cell Transplant in Second Line Relapsed or Refractory Large B-Cell Lymphoma. News Release. June 28, 2021. Accessed June 29, 2021. https://bit.ly/2SBcMuj