Real-World Outpatient CAR T-Cell Administration Insights Show Improved Safety and Feasibility in NHL

Advances in the management of CAR T-cell therapy–related toxicities, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), have substantially improved the safety and feasibility of outpatient axicabtagene ciloleucel (Yescarta; axi-cel) and brexucabtagene autoleucel (Tecartus; brexu-cel) administration for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to Radhika Bansal, MBBS. However, Bansal noted that further understanding of these agents’ safety profiles is still needed to optimize management strategies.

Findings from an exploratory analysis of real-world outpatient effectiveness of CAR T-cell therapy in patients with NHL were presented at the 2024 EHA Congress. Among patients who received axi-cel or brexu-cel between January 2018 and December 2022 (n = 155), 81% experienced CRS and 55% had ICANS within 30 days of CAR T-cell infusion. Notably, the median time to CRS resolution in the outpatient setting was 4.5 days for patients in the early management period (EMP; n = 34) vs 6 days for those in the late management period (LMP; n = 105; P < .01).

A subsequent analysis of hospitalization rates in the outpatient setting showed that 29% of patients in the EMP group and 44% of those in the LMP group were hospitalized within 3 days following CAR T-cell infusion. Early hospitalization occurred for 40% of patients in the overall population (n = 138). The primary reason for hospitalization was fever, which occurred in 82% of all patients. Tocilizumab (Actemra) was administered to 57% of patients, with 80% and 52% of patients in the EMP and LMP groups, respectively, receiving the agent during their first hospitalization within 3 days of infusion. Additionally, the EMP group had a shorter median duration of first hospitalization (6 days; interquartile range [IQR], 4-9) vs the LMP group (10 days; IQR, 6-13; P < .01).

“Our study shows that patients in the EMP group had a better safety profile and may even have had better responses [to CAR T-cell therapy],” Bansal, a postdoctoral fellow at the Mayo Clinic in Rochester, Minnesota, stated in an interview with OncLive^®.

In the interview, Bansal discussed the rationale for analyzing trends with outpatient CAR T-cell therapy in NHL, reported improvements in hospitalization rates and toxicity management observed over time in the current analysis, and detailed the potential use of digital tools and community paramedics to enhance outpatient care.

OncLive: What was the rationale behind analyzing trends in toxicity management and hospitalization rates with outpatient CAR T-cell therapy in patients with relapsed/refractory NHL?

Bansal: Traditionally, CAR T-cell [products] have been administered in the inpatient setting due to the risk of early onset of adverse effects [AEs] like CRS and ICANS. Our group at Mayo Clinic in Rochester previously demonstrated that outpatient administration of CAR T-cell therapy is safe and feasible. [In that study], overall, the hospitalization rate was 73%, and only 31% of patients required hospital admission in the first 3 days after CAR T-cell infusion. We wanted to explore trends in outpatient CAR T-cell therapy management, given the recent and ongoing changes in the management of AEs [associated] with axi-cel and brexu-cel.

What patient population was included in this analysis?

Patients with relapsed/refractory NHL who received axi-cel or brexu-cel between 2018 and 2022 at Mayo Clinic in Rochester were selected for this retrospective study. In this study, patients who received CAR T-cell therapy after November 2021 were [classified as the early management [cohort], because that is when the management of CRS and ICANS was changed in cohorts 4 and 6 of [the phase 1/2] ZUMA-1 trial [(NCT02348216) investigating axi-cel in patients with refractory large B-cell lymphoma]. Patients [who received CAR T-cell therapy through October 2021] were listed as the late management [cohort].

How did hospitalization rates within 3 days and 30 days of infusion compare between the EMP and LMP?

The most common reason for hospital admission across both groups was fever. However, patients who were admitted in the first 30 days after CAR T-cell therapy infusion had a higher rate of tocilizumab use. [There was a] shorter duration of hospitalization in the EMP.

What percentage of patients experienced CRS or ICANS within 30 days of infusion? How did these rates differ between the early and late management groups?

In the first 30 days after CAR T-cell infusion, 81% of the patients had CRS, and 55% of the patients had ICANS. In the first 3 days of CAR T-cell infusion, these numbers were significantly lower in the EMP [vs the LMP]. Overall, the median time to CRS resolution was significantly shorter in the EMP [vs the LMP].

What do these study findings indicate about the feasibility of outpatient CAR T-cell therapy administration?

Outpatient administration of CAR T-cell therapy is safe and feasible, and our findings are in line with what has been previously published in other studies. This study provides an opportunity to explore the future impact of the early management of AEs following CAR T-cell infusion. There’s also an opportunity to improve existing outpatient CAR T-cell [therapy administration] in practice by including digital tools and involving community paramedics. These would the next steps for our research.

Reference

Bansal R, Hsu H, Paludo J, et al. Updated trends in real-world outpatient (OP) administration of axicabtagene ciloleucel (axi-cel) and brexucabtagene autoleucel (brexu-cel) in relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). Presented at: 2024 EHA Congress; June 13-16, 2024; Madrid, Spain. Abstract P1191.