Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in the United Kingdom: A real-world intention-to-treat analysis

Abstract

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19 CAR T-cell product, approved for relapsed/refractory (r/r) mantle cell lymphoma (MCL). In ZUMA-2, brexu-cel demonstrated impressive responses in patients failing ≥2 lines, including a bruton's tyrosine kinase inhibitor, with an overall and complete response rate of 93% and 67%, respectively. Here, we report our real-world intention-to-treat (ITT) outcomes for brexu-cel in consecutive, prospectively approved patients, from 12 institutions in the United Kingdom between February 2021 and June 2023, with a focus on feasibility, efficacy, and tolerability. Of 119 approved, 104 underwent leukapheresis and 83 received a brexu-cel infusion. Progressive disease (PD) and/or manufacturing (MF) were the most common reasons for failure to reach harvest and/or infusion. For infused patients, best overall and complete response rates were 87% and 81%, respectively. At a median follow-up of 13.3 months, median progression-free survival (PFS) for infused patients was 21 months (10.1-NA) with a 6- and 12-month PFS of 82% (95% confidence interval [CI], 71-89) and 62% (95% CI, 49-73), respectively. ≥Grade 3 cytokine release syndrome and neurotoxicity occurred in 12% and 22%, respectively. On multivariate analysis, inferior PFS was associated with male sex, bulky disease, ECOG PS > 1 and previous MF. Cumulative incidence of non-relapse mortality (NRM) was 6%, 15%, and 25% at 6, 12, and 24 months, respectively, and mostly attributable to infection. Outcomes for infused patients in the UK are comparable to ZUMA-2 and other real-world reports. However, ITT analysis highlights a significant dropout due to PD and/or MF. NRM events warrant further attention.

Figure 1

Flowchart of mantle cell lymphoma patients approved, harvested, and infused with brexu‐cel February 2021–June 23.

Figure 2

(A, B) Cumulative incidence of non‐relapse mortality from infusion for all patients (A) and by age (B). NRM, non‐relapse mortality.

Figure 3

(A–C) Progression‐free survival (PFS) from approval (A), apheresis (B), and infusion (C) by Kaplan–Meier analysis.

Figure 4

(A–C) Overall survival (OS) from approval (A), apheresis (B), and infusion (C) by Kaplan–Meier analysis.

Figure 5

(A, B) Progression‐free survival outcome (A) and overall survival outcome (B) for infused patients with/without manufacturing failure.

Figure 6

(A, B) Progression‐free survival outcome (A) and overall survival outcome (B) for all patients harvested with/without manufacturing failure. Note that the groups should not be directly compared as they are defined by events that occur at different points after the date of apheresis. For example, patients who had manufacturing failure and subsequent infusion must have had stable disease for long enough to undergo a second apheresis and receive the infusion to be counted in that group.