Axicabtagene Ciloleucel Manufacturing Experience from Launch to Present Day: A United States Perspective

Axicabtagene ciloleucel (axi-cel) is approved globally for the treatment of relapsed/refractory large B-cell lymphoma (R/R LBCL). Axi-cel is an autologous anti-CD19 chimeric antigen receptor T-cell therapy that is manufactured at 3 sites (El Segundo, CA, USA; Frederick, MD, USA; and Amsterdam, Netherlands), and has a network of over 300 authorized treatment centers worldwide. The manufacturing process (Better M, et al. Cell Gene Ther Insights. 2017) and the manufacturing experience with axi-cel for patients (pts) in Europe (Van de Wiel L, et al. EBMT 2021. P017; Van de Wiel L, et al. EBMT 2023. P198) have previously been presented. Here, we describe the commercial manufacturing experience for pts with R/R LBCL treated with axi-cel in the United States from launch through present day. Patients with R/R LBCL registered on KiteKonnect™ and leukapheresed for axi-cel manufacturing during a 5.5-year period from Nov 3, 2017, to May 18, 2023, were included in this analysis. Data were extracted as of June 2, 2023. Manufacturing success rate: percentage of those pt lots dispositioned as quality released or released for clinical review out of the total number of lots dispositioned. First-pass manufacturing success rate: percentage of first manufacturing attempt pt lots dispositioned as quality released from the total number of first manufacturing attempt pt lots dispositioned, plus those terminated during that time (excluding those terminated for withdrawn pts). Delivery success rate: percentage of pt lots shipped from the total number of pts leukapheresed (excluding those pt lots in process and pts withdrawn). Turnaround time was defined as time from date of leukapheresis to date of quality release of final product. In total, 6665 pts from the United States with R/R LBCL were registered on KiteKonnect™ and leukapheresed between Nov 3, 2017 – May 18, 2023 (Table). The median turnaround time was 16 days (range, 15-49). A total of 6203 pt lots were delivered to treatment centers, resulting in a manufacturing success rate of 96% and a delivery success rate of 97%. First-pass manufacturing success rate was 93%. Patient outcomes are likely to depend on rapid and reliable manufacturing, as real-world experience examining time from leukapheresis to infusion has suggested (Locke FL, et al. Blood. 2022[Suppl 1]:7512-7515; Tully S, et al. J Clin Oncol. 2019). The ability to manufacture and quality release 93% of all pt lots dispositioned at first manufacturing attempt is critical to maintaining a timely and dependable manufacturing process and reinforces the high manufacturing and delivery success rates observed. Results from the past 5.5 years of experience demonstrate a robust and reliable commercial axi-cel manufacturing capability with high delivery and manufacturing success rates and consistent turnaround times for pts with R/R LBCL in the United States.