Outcomes of second-line axicabtagene ciloleucel for large B-cell lymphoma in the UK.

Following approval of axicabtagene ciloleucel (axi-cel) as second-line (2 L) treatment for large B-cell lymphoma (LBCL), results from real-world CAR T cohorts will be key to confirm safety and efficacy in standard practice. We present comprehensive clinical outcomes of LBCL patients intended to be treated with 2 L axi-cel through the UK National CAR T service. Of 345 patients approved for 2 L axi-cel, 302 (87.5%) were infused. The median age was 62 years (range 22-78); 21% were over 70 years. 75% of patients were approved for CAR T within 3 months from end of first-line (1 L) therapy. 42% of patients required pre-apheresis holding therapy, and 97% received bridging therapy. The best overall response rate was 86% (64% complete response). The 12-month OS was 73.9% (95% CI: 68.3-78.7) for infused patients and 1.5 months (0.9-3.0) for patients not proceeding to CAR T. The 12-month PFS was 52.4% (46.3-58.0). In multivariable analysis, advanced stage, male sex, no response to 1 L therapy, high LDH, and high CRP pre-infusion were independently associated with PFS. Grade ≥3 CRS and ICANS rates were 5% and 18%, respectively. Outcomes in patients aged ≥70 years were similar to the younger population. In this large UK real-world cohort of 2 L axi-cel in LBCL, we demonstrate efficacy and toxicity outcomes comparable to the pivotal ZUMA-7 trial, despite 42% patients requiring urgent holding therapy. Outcomes were favorable in patients aged ≥70 years, supporting the use of 2 L CAR T in older fit patients.