Abstract
Introduction: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL), with curative potential demonstrated in this setting (Westin et al NEJM. 2023; Neelapu et al Blood 2023). Studies have shown that time to CAR T infusion may impact patient outcome (Locke et al Blood Adv 2025; Tan et al Eur J Haematol 2025). Timely CAR T treatment is dependent on a variety of factors, including manufacturing slot availability and turnaround time, as well as the coordination of healthcare teams at the treatment and referral centres. Given the vast geography of Canada, characterization of the patient journey to CAR T therapy starting from first CAR T eligibility (i.e. at relapse) is critical to identify non-clinical treatment barriers and optimize timely axi-cel infusion.
Objective: To describe the 4-year real world experience of pts treated with axi-cel in Canada, including manufacturing experience and impact of patient location relative to treatment centre on time to axi-cel infusion.
Methods: This is a retrospective review of adult pts with R/R LBCL registered on Kite Konnect® and apheresed for commercial axi-cel treatment between Nov 1, 2019- Nov 30, 2023 in Canada. Fresh apheresis material collected from pts at authorized treatment centres (ATCs) were shipped to Kite for manufacturing. Finished product lot remained at the manufacturing facility until Quality Assurance (QA) release as per Health Canada's Good Manufacturing Practice requirements and shipped to the ATC. Data is reported as 1) Full Analysis Set (FAS) and 2) ATC Analysis Set (ATC Data). FAS includes pts registered in Kite Konnect® and apheresed for axi-cel manufacturing. FAS analysis was conducted using data from Kite Konnect® for all ATCs in Canada. ATC Data includes pts in the FAS who were treated at 4 ATCs and includes data from patient charts on timelines from disease relapse, referral and consult, as well as referral centre information relative to the ATC. Referral centre information includes whether the patient was an in-province or out-of-province referral. In-province referrals were further defined as pts originating within the ATC, including those who may be co-managed by ATC and referring centre, compared to those referred to the ATC (e.g. not known to ATC).
Results: A total of 506 pts were registered on Kite Konnect® website and provided apheresis material for axi-cel manufacturing (FAS), and the vast majority (n=500) of the pts were treated in third-line or later. A total of 87 pts (23.3%) were out-of-province referrals. Among all pts, the manufacturing success rate was 98.2%, with a 96.2% first-pass manufacturing success rate. Overall, 88.3% (N=447) were infused with axi-cel, and this infusion rate did not differ between out-of-province and in-province referrals, with rates of 88.9% and 88.2% respectively. The median turnaround time (Q1, Q3) from date of apheresis to QA release was 18 days (17, 19), with a range of 16-28. The median time from apheresis to infusion (Q1, Q3) was 33 days (29, 38), with a range of 25-292.
Among the ATC data set (N=372), 77% (N=285) of pts were in-province referrals, and among these 59.3% (N=169) originated within the ATC. The median time from relapse to apheresis (Q1, Q3) was 34 days (20, 48). Pts who were out-of-province referrals had a significantly longer median time from relapse to apheresis of 44 days (32, 58), compared to 29 days (18, 43) for in-province referrals (p<0.001). Among in-province referrals, pts who originated within the ATC had a shorter median time from relapse to apheresis of 23 days (14, 39), compared to 37 days (24, 55) for pts referred to the ATC (p<0.001). The median time from apheresis to infusion was 33 days regardless of patient location.
Conclusions: First 4 years of experience in manufacturing commercial axi-cel for pts treated in Canada shows high manufacturing success (98%), with rapid and reliable time from apheresis to product release of 18 days. Pts who were referred from out of province and those not known to ATC experienced longer time from relapse to apheresis compared to pts who originated at the ATC, while there was no difference in time from apheresis to infusion. Optimizing timely patient identification and referral, and developing additional CAR T treatment centres across the country may improve time to axi-cel infusion in Canada for these pts.
