Outpatient Versus Inpatient Axicabtagene Ciloleucel CAR T-Cell Therapy in Non-Hodgkin’s Lymphoma: Insights From A US Multicenter Transplant and Cellular Therapy Network

Axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is approved for treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Due to risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), it is typically administered in an inpatient (IP) setting. Emerging data suggest outpatient (OP) administration, supported by structured care pathways, prophylactic dexamethasone, and remote patient monitoring (RPM), may offer comparable outcomes. However, real-world evidence on OP use remains limited. The primary objective was to compare clinical outcomes, safety, and healthcare utilization of axi-cel in OP versus IP settings. This retrospective study included adults with DLBCL who received axi-cel outside of clinical trials across five centers in a multi-state US transplant network (January 2019 to June 2023). OP eligibility was based on institutional protocols and enrollment in an RPM platform. Association between therapy setting and CRS/ICANS, overall survival (OS), and progression-free survival (PFS) was assessed using multivariable logistic and Cox regression models, adjusted for age, tumor burden, comorbidities, performance status, and prophylactic dexamethasone use. Among 143 eligible patients, 47 (33%) received OP therapy, with uptake increasing over time (36% in 2022, 64% in 2023). OPs were older (median 65 years OP vs. 60 years IP; P < .001) and more likely to receive prophylactic dexamethasone (89% OP vs. 21% IP; P < .001). There were no notable differences in other clinicodemographic and socioeconomic characteristics. The median hospital length of stay (LOS) was shorter for OPs (7 vs. 15 days; P < .001) with similar ICU utilization between groups (28% OP vs. 23% IP; P = .54). Notably, 13% of OPs avoided any post-infusion hospitalization. CRS occurred in 85% of all patients, with no difference by setting (83% OP vs. 85% IP; P = .89) and CRS grade ≥2 was comparable (47% OP vs. 46% IP; P = .519). In OPs ICANS was less frequent (34% OP vs. 56% IP; P = .020) and less severe (grade ≥2: 17% for OP vs. 33% for IP; P = .006) possibly due to higher prophylactic dexamethasone use in this group. Reactive steroid use was observed in 53% OP vs. 36% IP; P = .085, with a shorter median duration in OP (3 days OP vs. 7 days IP; P < .001). Multivariable models showed no significant association between therapy setting and CRS grades ≥2 (OR: 0.77; 95% CI: 0.29-2.01; P = .584), ICANS any grade (OR: 0.69; 95% CI: 0.67-0.72; P = .270), OS (HR: 0.63; 95% CI: 0.26-1.50; P = .301). OP therapy was not associated with worse PFS (HR: 0.59; 95% CI: 0.54-1.62; P = .151). OP administration of axi-cel, supported by RPM, was associated with reduced hospitalization, while having comparable toxicities and survival outcomes as IP administration. These findings support broader adoption of OP axi-cel delivery in appropriately selected patients.