Paper Details

ABSTRACT

Background: CD19 CAR-T therapy with axicabtagene ciloleucel (axi-cel) is approved for the treatment of relapsed/refractory large B-cell lymphoma (R/R LBCL). Given the risk of CRS and ICANS, axi-cel is traditionally administered in the inpatient setting. Outpatient administration has been reported using resource-intensive models incorporating specialized home monitoring and 24-hour nursing support, including the phase II ZUMA-24 trial (Leslie et al, Am J Cancer Res 2025). However, implementation of these approaches requires substantial healthcare resources, limiting their broader adoption. The Ottawa Hospital (TOH) administers axi-cel in the outpatient setting without dedicated home nursing or remote monitoring. Here we report the institutional approach and associated toxicity outcomes.

Methods: This was a retrospective, single-centre, descriptive study using the TOH Transplant and Cellular Therapy database. Patients ≥18 years with R/R LBCL treated with commercial axi-cel at TOH between Feb 2021 and May 2025 were included if they had at least 3 months of follow-up. Patients were enrolled in the outpatient program if they had a reliable caregiver available 24 hours/day, resided within a 30-minute drive to TOH, and had no physician-identified factors conferring a high risk of treatment-related toxicity. Patients and caregivers had 24-hour telephone access to the on-call hematologist, who determined the need for inpatient admission and admitted directly to the inpatient unit, bypassing the emergency department.

Results: 133 patients received axi-cel for R/R LBCL, with 60 intended for the outpatient program. In the outpatient intended cohort, the median age was 63 years (range 25–82) and 41 (68.3%) were male. Patients received a median of 2 prior lines of therapy (range 1-5). ECOG performance status was 0 in 10 patients (16.7%), 1 in 43 (71.7%), and 2 in 7 (11.7%). Primary refractory disease was present in 12 patients (20%). Median LDH at baseline was 256 U/L (range 165–2399). The majority had DLBCL-NOS (35, 58.3%), followed by transformed FL (10, 16.7%), HGBL (7, 11.7%), FL (5, 8.3%), PMBCL (2, 3.3%), and MZL (1, 1.7%). Ten patients (16.7%) had a prior autologous stem cell transplant. Median HCT-CI comorbidity score was 1 (range 0–5). 31 patients (51.7%) received bridging therapy. There were no significant differences in baseline characteristics between the inpatient and outpatient intended cohort, except that more patients received axi-cel in second line in the outpatient intended cohort (20 vs 5.5%), consistent with the time of outpatient program implementation (p=0.04).

In the outpatient intended cohort, the median total number of days of admission for CAR-T (inpatient plus outpatient) was 24.5 days (range 10-57), with 1 patient (1.7%) avoiding inpatient admission. The median number of days spent in the outpatient program was 12.5 days (range 3-34) and inpatient stay (including time in ICU) was 10 days (range 0-54). Among patients who underwent inpatient admission from outpatient, 7 (11.9%) were admitted before CAR-T infusion, 8 (13.6%) on the day of CAR-T infusion, and the remaining 44 (74.6%) were admitted between days 1-9 post infusion. 750 total days were spent as inpatient and 825 total days were spent as outpatient, with 50.2% of outpatient days occurring after inpatient stay, signifying that patients still went to outpatient program after inpatient stabilization.

The most common reason for inpatient admission was fever (n=44, 74.6%). Any-grade CRS occurred in 58 patients (96.7%), with max grade 3 in 1 (1.7%) and no grade 4 or 5 events. Median onset and duration of CRS was 2 days (range 1-10) and 6 days (range 2-11), respectively. Any-grade ICANS occurred in 35 patients (58.3%), with grade 3 or 4 in 7 patients (11.7%). Median onset and duration of ICANS was 6 days (range 3-14) and 6 days (range 2-16), respectively. 14 patients (23.3%) required ICU transfer, most commonly for CRS or ICANS (n=5), with a median ICU length of stay of 2 days (range 1-9). Notably, no patients were immediately transferred to ICU upon inpatient admission.

Conclusion: This single-centre Canadian experience demonstrates that outpatient administration of axi-cel for R/R LBCL is feasible, enabling patients to spend more days in the outpatient program, with shorter hospital inpatient days. These institutional processes may inform other centres seeking to optimize resource use while maintaining patient safety during CAR T-cell therapy delivery.