Axicabtagene ciloleucel demonstrated a 2.5-fold increase in individuals with relapsed/refractory large B-cell lymphoma who were alive at 2 years and did not experience either cancer progression or require the need for additional cancer treatment.
Axicabtagene ciloleucel (Yescarta; Kite) demonstrated statistically significant improvements in overall survival (OS) compared to historical treatment for relapsed/refractory large B-cell lymphoma (R/R LBCL) within 12 months of completion of first-line therapy, according to results of the phase 3 ZUMA-7 (NCT03391466) study.
The historical treatment for R/R LBCL, which has been used as the standard of care in a curative setting for approximately 30 years, includes a multi-step process involving platinum-based salvage combination chemoimmunotherapy regimen followed by high-dose therapy and stem cell transplantation for those who respond to the salvage chemotherapy.
OS was designed as a prespecified key secondary endpoint, which was defined as the length of time from randomization to death from any cause. ZUMA-7 was considered a landmark trial, as the first and largest phase 3 study of any chimeric antigen receptor (CAR) T-cell therapy and had the largest follow-up. Axicabtagene ciloleucel demonstrated superior event-free survival (EFS) compared with the historical standard of care treatment, which was the trial’s primary endpoint.
Data from this trial led to the approval for the initial treatment of R/R LBCL in April 2022 in the United States and approval in October 2022 in the European Union. Other approvals included Great Britain, Israel, Japan, and Switzerland.
ZUMA-7 included 359 individuals in 77 centers around the world who were randomized 1:1 to receive a single infusion of axicabtagene ciloleucel or the historical standard of care second-line treatment.
The primary endpoint was determined by blinded central review. EFS was defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause.
Axicabtagene ciloleucel demonstrated a 2.5-fold increase in individuals who were alive at 2 years and did not experience either cancer progression or require the need for additional cancer treatment at 40.5% and 16.3% for the standard of care.
Additionally, investigators found a 4-fold greater median EFS at 8.3 months and 2 months, respectively. Furthermore, individuals on axicabtagene ciloleucel did not receive additional bridging chemotherapy, which could have confounded the results.
Nearly 3 times as many individuals randomized to axicabtagene ciloleucel ultimately received the definitive CAR T-cell therapy treatment at 94% compared to those randomized to the standard of care at 35%. More individuals responded to axicabtagene ciloleucel, with an overall response of 83% compared to 50% for those on the standard of care. A complete response was seen at 65% and 32%, respectively.
At the time of the primary EFS analysis, more than half of the individuals in the standard of care arm subsequently received axicabtagene ciloleucel off study.
Investigators reported that the safety profile was consistent with previous studies, with adverse events including cytokine release syndrome and neurologic events.
ZUMA-7 was conducted under a special protocol assessment with the FDA in which the design, clinical endpoints, and statistical analysis were agreed upon in advance with the agency. The pre-specified analysis was also agreed by other health authorities.
The full results of the study will be presented later this year at an upcoming scientific meeting.
Kite’s Yescarta CAR T-cell therapy demonstrates a statistically significant improvement in overall survival for initial treatment of relapsed/refractory large B-cell lymphoma. News release. Gilead. March 21, 2023. Accessed March 22, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/3/kites-yescarta-car-t-cell-therapy-demonstrates-a-statistically-significant-improvement-in-overall-survival-for-initial-treatment-of-relapsedrefract