Outpatient lymphodepletion prior to brexucabtagene autoleucel (brexu-cel; Tecartus) appears to be a safe and effective strategy for patients with B-cell acute lymphoblastic leukemia (B-ALL) and mantle cell lymphoma (MCL), according to a retrospective study presented at the 2024 ASH Annual Meeting. The findings suggest that administering lymphodepletion in the outpatient setting does not compromise patient outcomes and may offer logistical advantages.
Key Findings on Mortality and Survival
The study revealed that patients who underwent lymphodepletion in the outpatient setting (n = 28), regardless of where the brexu-cel infusion occurred, had a 60-day non-relapse mortality rate of 3.6% (95% CI, 0.25%-16%). This was comparable to the 7.1% (95% CI, 1.2%-21%) observed in patients who received both lymphodepletion and brexu-cel in the inpatient setting (n = 28). Furthermore, the 6-month progression-free survival (PFS) rate was notably high in the outpatient arm at 83.3% (95% CI, 60.5%-93.5%), compared to 71.1% (95% CI, 50.8%-87.6%) in the inpatient arm.
Study Design and Patient Population
The retrospective study included adult patients with B-ALL or MCL treated with brexu-cel at City of Hope between November 1, 2020, and March 31, 2024. Patients were categorized into two groups: those receiving lymphodepletion in the outpatient setting and those receiving it in the inpatient setting. To ensure comparability between the groups, investigators used a propensity score nearest matching method, considering factors such as ECOG performance status, severe comorbidity score, bulky disease (for B-ALL patients), and the MCL International Prognostic Index score (for MCL patients).
The primary endpoint of the study was the rate of 60-day non-relapsed mortality. Secondary endpoints included the incidence of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), inpatient admission rates for those initially treated as outpatients, best complete response (CR) rate, and 6-month PFS rate.
The overall patient population (n = 56) consisted of 66% B-ALL and 34% MCL cases, with a median age of 55 years (range, 23-80). The majority of patients were male (77%) and Hispanic White (61%), with an ECOG performance status of 0 to 1 (93%) and higher disease burden (75%). Patients had received a median of 4 prior lines of therapy (range, 1-11), with 23% having undergone a prior allogeneic stem cell transplant and 7.1% a prior autologous stem cell transplant.
Safety and Toxicity
Safety data indicated that any-grade CRS occurred in 86% of patients in the outpatient arm and 82% in the inpatient arm. Grade 3 or higher CRS rates were 7.1% and 14%, respectively. The median duration of CRS was 4 days in both arms. Any-grade ICANS was reported in 54% of outpatient and 61% of inpatient cases, with grade 3 or higher ICANS rates of 29% and 25%, respectively. The median duration of ICANS was 4 days (range, 1-41) in the outpatient arm and 7 days (range, 1-73) in the inpatient arm. Tocilizumab was administered for toxicity to 79% of outpatient and 75% of inpatient patients, with a median of 2 doses in both arms.
Clinical Implications
"Brexu-cel is safe to administer [in the outpatient setting] with similar efficacy and non-relapse mortality," noted lead study author Tamer Othman, MD, PhD, of City of Hope. However, Othman also emphasized the need for larger studies with longer follow-up to validate these findings. These results suggest a potential shift towards more convenient outpatient administration of lymphodepletion before brexu-cel, which could improve patient access and reduce healthcare costs without compromising safety or efficacy.
