Outcomes of outpatient chimeric antigen receptor T-cell therapy administration: A single center experience at an urban hospital Free

Introduction: Since initial approval in 2017, chimeric antigen receptor T-cell therapy (CAR-T) has transformed outcomes for hematological malignancies. CAR-T has traditionally been administered in the inpatient (inpt) setting, due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). As reported by Hansen et al in Cancers, outpatient (outpt) CAR-T administration has been shown to have a favorable safety profile and lower financial toxicity. Many institutions have strict guidelines for selecting outpt treatment candidates, including caregiver support, proximity to the hospital, and infrastructural support within the institution. In this single-center institutional study, we assess the safety and efficacy of outpt CAR-T administration at an urban hospital.

Methods: We retrospectively collected data from all patients who received CAR-T therapy from May 2016 to September 2024 at Karmanos Cancer Institute in Detroit, Michigan. Data was stratified by inpt and outpt CAR-T administration. We selected only patients with multiple myeloma (MM) or diffuse large B-cell lymphoma (DLBCL) for this study.

Baseline patient characteristics were summarized using counts and percentages for categorical variables, and medians with ranges for continuous variables. Group comparisons based on inpt versus outpt status were performed using the chi-square test or Fisher's exact test for categorical variables, and the Wilcoxon rank-sum test for continuous variables. Overall survival (OS) was defined as the time from CAR-T administration to death from any cause. Relapse-free survival (RFS) was defined as the time from CAR-T administration to documented relapse or death, whichever occurred first. Kaplan–Meier methods were used to estimate survival distributions for OS and RFS. Follow-up time was estimated using the reverse Kaplan–Meier method. Survival distributions were compared using the log-rank test. The proportional hazards assumption was evaluated using Schoenfeld residuals. Where the proportional hazards assumption was held, Cox proportional hazards regression was used to derive hazard ratios. In cases where the assumption was violated, a weighted Cox regression model was applied.

Results: During the study period, 174 patients received CAR-T. 143 patients were treated inpt, and 31 patients were treated outpt. Most patients treated in the outpt setting had DLBCL (77.4%, p = 0.027). In the outpt cohort, 14 patients received tisa-cel, 7 patients received ida-cel, 6 patients received liso-cel, and 4 patients received axi-cel. The inpt cohort received cilta-cel, brexu-cel, or other products in addition to the aforementioned therapies. Interestingly, there was not a statistically significant difference in CRS between the inpt (75.68%) and outpt (55.0%) cohorts (p = 0.099). There was no statistically significant difference in incidence of ICANS, infectious complications, or cardiac complications between inpt and outpt cohorts. 35.5% of patients in the outpt cohort required readmission within 100 days. The median duration of hospitalization for readmitted patients in the outpt cohort was 6 days, the median duration of overall hospitalization for the inpt cohort was 11 days, and this was statistically significant (p = 0.008). Incidence of ICU admission was 3.23% and 14.0% in the outpt and inpt cohort respectively, which was not statistically significant (p = 0.21). With median follow up of 2.05 years and 1.77 years, median overall survival (OS) was 2.15 years (95% CI, 1.48 to NR) and 4.24 years (95% CI, 2.17 to NR) for outpt and inpt cohorts respectively, but was not statistically significant. Similarly, relapse free survival (RFS) was not statistically different between the two groups. Additionally, there was not a statistically significant relationship between age, and whether CAR-T was administered inpt or outpt.

Conclusions: Outpt infusion of CAR-T cells was safe and post CAR-T cell outcomes did not differ based on inpt vs. outpt infusion. In fact, the readmitted patients in the outpt cohort had a shorter hospital duration compared to patients treated inpatient, which was statistically significant. Outpt infusion of CAR T cells can reduce the burden of hospitalization for these patients.