Data from a pivotal study of axicabtagene ciloleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for the treatment of patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) with ≥ 2 prior systemic therapies, was presented at the 2021 American Society of Hematology (ASH) Annual Meeting to highlight survival findings.

“In the 2-year analysis of ZUMA-1, the multicenter, single-arm phase 1/2 study evaluating axicabtagene ciloleucel in patients with refractory LBCL, the objective response rate (ORR) was 83 percent, including a complete response (CR) rate of 58 percent; 39 percent of patients had ongoing response with a median follow-up of 27.1 months (Locke et al. Lancet Oncol. 2019). Event free survival (EFS) is emerging as a robust surrogate endpoint for overall survival (OS) in hematologic malignancies,” explained Caron Jacobson, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

A total of 111 patients with refractory LBCL were enrolled and axicabtagene ciloleucel was administered to 101 patients. The median follow-up was 51.1 months as of August 11, 2020. After leukapheresis at enrollment, low-dose conditioning chemotherapy was administered to the patients followed by a target dose of 2×10⁶ anti-CD19 CAR T cells/kg.

The primary endpoint was objective response rate (ORR) and the first response assessment occurred 4 weeks after infusion. 

In patients with over 4 years of follow-up, the median OS was 25.8 months and the OS rate was 44 percent. In patients treated with axicabtagene ciloleucel, the EFS was 5.7 months with a 12-month rate of 43 percent (95% CI, 33-52), and a 24-month rate of 38 percent (95% CI, 28-47). In patients with an EFS event by month 12, the 4-year OS rates were 7 percent (95% CI, 2-16) versus 91 percent (95% CI, 78-97) in those without. No new safety signals were reported since the 2-year analysis, and there were no serious adverse events, no axi-cel-related secondary malignancy, and no confirmed cases of replication-competent retrovirus.

“These data support the use of EFS as a surrogate endpoint for long-term OS in refractory LBCL, and the relationship between EFS and 5-year OS will be presented,” concluded Dr Jacobson and colleagues.

Caron J, Locke FL, Ghobadi A, et al. Long-Term (4- and 5-Year) Overall Survival in ZUMA-1, the Pivotal Study of Axicabtagene Ciloleucel (Axi-Cel) in Patients with Refractory Large B-Cell Lymphoma (LBCL). Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 1764.