The impact of distance to CAR-T centre on CAR-T delivery and CAR-T outcomes: A single centre retrospective cohort study

Abstract

Abstract Background: Chimeric Antigen Receptor T-cell (CAR-T) therapy has transformed the treatment landscape for relapsed and refractory B-cell malignancies. There is limited understanding of how Canada's large geographic area impacts CAR-T delivery and treatment response. Purpose: To evaluate the impact of distance to CAR-T centre on referral-to-infusion time, T-cell harvest to CAR-T infusion (vein-to-vein) time, bridging therapy use, treatment response, overall survival (OS), and immunoglobulin replacement practices. Methods: This single-centre retrospective cohort study included adults receiving CAR-T therapy at the Juravinski Cancer Centre (JCC) in Hamilton, Ontario between January 2020 and September 2024. Prospectively collected data was gathered from a local CAR-T patient registry. Patients were assigned to 4 distanced based cohorts (<20 km, 20-59.9 km, 60-149.9 km, and ≥150 km from the JCC based on postal code), and to either a CAR-T or non-CAR-T centre (referring centre) cohort. ANOVA, Wilcox rank sum test, and chi-square tests were used to determine predictors of referral-to-infusion time, vein-to-vein time, bridging therapy use, rates of complete and partial response (CR/PR), and immunoglobulin replacement. Kaplan-Meier and log-rank tests were used to assess OS. Results: Of the 146 patients included in this study, there was no significant difference in age, disease pathology, previous lines of therapy, or CAR-T products used amongst the CAR-T centre or non-CAR-T centre cohorts. Median referral-to-infusion times did not differ between distance cohorts, <20 km, 20-59.9 km, 60-149.9 km, and ≥150 km (43, 44, 42, and 47 days; p=0.79). Median vein-to-vein times also did not differ (41, 36, 37, and 37 days; p=0.15). Bridging therapy use differed amongst distance cohorts (85.2%, 83.3%, 69.6%, and 48% (p=0.005)). There was no significant difference in CR/PR rates amongst distance cohorts (59.3%, 47.8%, 54.6%, and 60% (p=0.96)). Distance did not predict immunoglobulin replacement rates (52%, 63%, 46%, and 44% receiving immunoglobulin products; p=0.55) or median duration of replacement (124, 135, 75, and 114 days; p=0.16). 53%, 57%, 67%, and 45% were documented as eventually discontinuing immunoglobulin products (p=0.69). 2-year OS was not significantly different amongst distance cohorts (57.5%, 37.5%, 42.7%, and 75.6% (p=0.079). Amongst treatment centre cohorts, median referral-to-infusion times were shorter in patients referred from a CAR-T versus a non-CAR-T centre (38 vs. 46 days; p=0.0071). Vein-to-vein times did not differ between CAR-T and non-CAR-T centre cohorts (37 vs. 36 days; p=0.84). CR/PR rates also did not differ between CAR-T and non-CAR-T centre cohorts (53.9% vs. 54.5%; p=0.96). More patients received bridging therapy in the CAR-T compared to the non-CAR-T centre cohort (92.3% vs. 66.4%; p=0.002). There was no significant difference in immunoglobulin use (58% vs. 50%; p=0.43) or median duration of replacement (154 vs. 133 days; p=0.89) in the CAR-T versus non-CAR-T centre cohorts; although more patients discontinued immunoglobulin replacement in the non-CAR-T centre cohort (34% vs. 58%; p=0.02). There was no significant difference in 2-year OS between CAR-T and non-CAR-T centre cohorts (43.8% vs. 54.5% p=0.84). Conclusions: Vein-to-vein time, treatment response, immunoglobulin replacement, and 2-year OS did not significantly differ amongst CAR-T centre and non-CAR-T centre cohorts, supporting the feasibility of CAR-T delivery across large geographic areas. Shorter referral-to-infusion times in the CAR-T centre cohort were likely due to singular physicians acting as both lymphoma and CAR-T providers, which did not affect vein-to-vein times. Patients residing further away or referred from non-CAR-T centres were less likely to require bridging therapy for disease control, suggesting that distant centres are referring a more stable patient population. Patients referred from non-CAR-T centres had higher immunoglobulin discontinuation rates, which may reflect centre-to-centre practice pattern variation. Future research comparing other CAR-T centres with large geographic disparities would be beneficial.