Andrea Kuhnl, Amy Kirkwood, Michael Northend, Caroline Besley, Ben Uttenthal, Jane E. Norman, Hwai Jing Hiew, Frances Seymour, Bernard Maybury, Wendy Osborne, Francesca Sillito, Ahmed Abdulgawad, Ceri Jones, Pierre C. McCarthy, Aikaterini Panopoulou, John G. Gribben, Edward Bataillard, Nicolás Martínez‐Calle, L. Gajendran, Maeve O'Reilly, Emil Kumar, Robert P. Wilson, Shenbagaram Kasivisvanathan, Nada Fadlelmula, Angharad Pryce, Olateni Awofisayo, Adrian Maraj, William Townsend, Kate Cwynarski, Shankara Paneesha, Amrith Mathew, Vaishali Dulobdas, Dima El‐Sharkawi, Thomas Creasey, Mary Warren, Ram Malladi, Mary Owen, Muddeha Waraich, Kushani Ediriwickrema, Joseph Froggatt, Alison Delaney, Andrew Davies, Rajesh Alajangi, Graham P. Collins, Robin Sanderson, Claire Roddie, Tobias Menne, Sridhar Chaganti
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.