CAR T-Cell Therapy Is Safe, Feasible in Outpatient Setting for NHL

The administration of CAR T-cell therapy in the outpatient setting was deemed feasible and safe in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to findings from an exploratory analysis of real-world outpatient effectiveness shared during the 2024 EHA Congress.

Outpatient administration of axicabtagene ciloleucel (Yescarta; axi-cel) and brexucabtagene autoleucel (Tecartus; brexu-cel) was evaluated by Radhika Bansal, MBBS, and colleagues.

“Further evidence is needed to understand the safety profile of axi-cel and brexu-cel to optimize management strategies,” lead author Bansal, a postdoctoral fellow at the Mayo Clinic in Rochester, Minnesota, said during a presentation of results.

In the retrospective study, a total of 155 patients with r/r NHL received axi-cel or brexu-cel between January 2018 and December 2022. At the data cutoff of November 2023, post infusion outcomes and toxicity management were compared in an early management period (EMP; n =34), from November 2021 through December 2022, and a late management period (LMP; n = 104), from January 2018 through October 2021.

Investigators reported that within 30 days of infusion, 81% of all patients experienced cytokine release syndrome (CRS), with 4% reporting grade 3 or higher, and 55% had immune effector cell-associated neurotoxicity syndrome (ICANS), with 19% reporting grade 3 or higher. Most AEs developed less than 14 days post infusion. No CRS was reported between 14 and 30 days post infusion. Six percent of patients experienced ICANS during that time period. Median CRS resolution was shorter in the EMP group vs the LMP group (4.5 vs 6 days; P < .01).

Reviewing hospitalization use in patients treated in the outpatient setting, 29% of patients in the EMP were admitted early (within 3 days post infusion) compared with 44% in the LMP (P = .137). In the overall population (n = 138), 40% of patients were admitted to the hospital early. Fever (82%) was the primary reason for hospitalization overall. Eighty percent of patients in the EMP group and 52% of patients in the LMP group received tocilizumab as treatment for first hospitalization within 3 days post infusion. Overall, 57% of patients received tocilizumab.

Patients in the EMP group had a shorter median duration of first hospitalization compared with patients in the LMP group (6 vs 10 days; P < .01). “Even though fewer patients were hospitalized and required fewer ICU visits in the early period, the difference did not reach statistical significance,” Bansal said.

Multivariate analysis in all patients treated in the outpatient setting revealed that elevated lactate dehydrogenase levels at day 0 were associated with increased odds of grade 3 or higher CRS/ICANS within 30 days of infusion (odds ratio, 2.8; 95% CI, 1.0-7.3). Further, bridging therapy was associated with odds of hospitalization within 3 days of infusion (odds ratio, 2.9; 95% CI, 1.2-6.7).

Baseline characteristics were comparable between the 2 groups. The median age for all patients was 60 years (interquartile range, 51.5-65) and the majority of patients were male (66%). A breakdown of disease subtype revealed that most patients were diagnosed with large B-cell lymphoma (LBCL; 84%) followed by follicular lymphoma (8%), mantle cell lymphoma (6%), and other (2%).

Investigators also conducted a subanalyses of patients with LBCL (n = 116) who received outpatient axi-cel that evaluated safety, hospitalization, and effectiveness and were stratified by EMP vs LMP. Median follow up was 16.5 months in the EMP and 41 months in the LMP.

In the subanalyses, “baseline characteristics, except prior lines of therapy and prophylactic steroid use, were comparable,” Bansal said. Twenty-four percent of patients in the EMP group required prophylactic dexamethasone vs 0% in the LMP (P < .0001).

Regarding CRS and ICANS in patients with LBCL, 83% of patients who received outpatient axi‑cel had CRS (3% had grade ≥3) and 51% had ICANS (17% had grade ≥3). Investigators wrote that CRS and ICANS did not vary significantly in the EMP vs LMP groups within 30 days post infusion (76% vs 85% CRS, P >.05; 40% vs 54% ICANS, P >.05). Similar to the overall population, median time to CRS resolution was shorter for patients in the EMP group vs the LMP group (4 vs 5 days; P < .05).

Turning to hospitalization admissions in patients with LBCL, 100% of patients in the EMP group received tocilizumab vs 48% of LMP patients within 3 days of infusion (P = .012). Bansal said intensive care unit (ICU) visits were only reported among patients in the LMP group, with no patients in the EMP group admitted to the ICU within 30 days of infusion (23% vs 0%; P < .01).

Outcomes effectiveness in patients with LBCL revealed a best overall response rate of 88% with an 84% complete response (CR) rate in patients in the EMP group vs 76% (59% CR rate) for patients in the LMP group. Bansal said median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were not reached in patients in the EMP group but among patients in the LMP group DOR, PFS, and OS were 12.9, 4.3, and 22.5 months, respectively.

Findings from this study align with previous studies evaluating outpatient CAR T-cell administration.2 “Our study provides further evidence that outpatient delivery of axi-cel and brexu-cel is safe and feasible,” Bansal said. “Earlier intervention with toxicity management strategies improves safety outcomes in patients with relapsed/refractory lymphoma and may improve effectiveness outcomes in patients with LBCL who received outpatient axi-cel,” Bansal concluded.

REFERENCES

1. 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 the 2024 European Hematology Association (EHA) Hybrid Congress; June 13-16, 2024; Madrid, Spain. Abstract P1191.
2. Bansal R, Paludo J, Corraes ADMS, et al. Outpatient practice utilization for CAR-T and T cell engager in patients with lymphoma and multiple myeloma. J Clin Oncol. 2023;41 (suppl 16):1533-1533. doi:10.1200/JCO.2023.41.16_suppl.1533