Axicabtagene Ciloleucel Significantly Improves Outcomes Over Standard Care as Second-Line Therapy for Large B-cell Lymphoma

Findings from the ZUMA-7 trial suggest axicabtagene ciloleucel, an autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, is an effective alternative to chemoimmunotherapy, high-dose chemotherapy, and autologous hematopoietic stem cell transplant (autoHSCT) as second-line treatment for relapsed or refractory large B-cell lymphoma.

The international, phase 3 trial enrolled 359 patients between January 25, 2018, and October 4, 2019. Patients were randomized in a 1:1 ratio to axicabtagene ciloleucel (n = 180) or standard care: 2 or 3 cycles of chemoimmunotherapy, followed by high-dose chemotherapy with autoHSCT in patients with a response to the chemoimmunotherapy (n = 179). The primary end point was event-free survival (EFS) per blinded central review. Secondary end points included response, overall survival (OS), and safety.

At a median follow-up of 24.9 months, the median EFS was 8.3 months with axicabtagene ciloleucel vs 2 months with standard care. The estimated EFS at 24 months was 41% vs 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P <.001).

In addition, 83% of the patients in the axicabtagene ciloleucel group experienced a response compared to 50% of the patients in the standard care group. Complete response rates were 65% and 32%, respectively.

Findings in an interim analysis estimated the 2-year OS was 61% with axicabtagene ciloleucel vs 52% with standard care.

Grade 3 or higher adverse events were reported for 91% of patients in the axicabtagene ciloleucel group vs 83% of patients in the standard care group. Grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 6% and 21% of patients receiving axicabtagene ciloleucel. No deaths due to CRS or neurotoxicity were reported.

“[Axicabtagene ciloleucel] therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects,” concluded study authors.

Source:
Locke F, Miklos D, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133.