(SLB-026) Comparative Effectiveness of Brexucabtagene Autoleucel for Relapsed or Refractory Mantle Cell Lymphoma: An External Control Arm Study Using Lymphoma Registry

Background: Brexucabtagene autoleucel (brexu-cel), a chimeric antigen receptor (CAR) T-cell therapy, received accelerated approval for treatment of refractory (r/r) mantle cell lymphoma (MCL). Before its approval, no effective treatment options were available after Bruton’s tyrosine kinase inhibitor (BTKi) failure. In the absence of randomized studies on brexu-cel, external control arms (ECA) study using real-world data (RWD) can provide comparative outcomes to inform treatment decisions.

Objectives: To evaluate overall survival (OS) and progression-free survival (PFS) associated with brexu-cel in patients with r/r MCL

Methods: Primary data sources included (1) published summary data from the ZUMA-2 study (NCT02601313; N=60 for efficacy set; 2016-2019) for brexu-cel and (2) individual patient data from the Samsung Medical Center-Lymphoma Cohort Study (SMC-LCS; NCT03117036; 2017-2023) for conventional treatments. ECA included those fulfilling the key eligibility criteria of ZUMA-2: r/r status after up to five prior treatment lines including BTKis. Index date was defined as the date of conventional treatment initiation after meeting eligibility criteria. Patients were followed from the index date to all-cause death for OS, disease progression or all-cause death for PFS, or last follow-up date. Kaplan-Meier survival curves from ZUMA-2 were digitized using Engauge Digitizer software (Version 12.1). Matching-adjusted indirect comparison (MAIC) was applied to balance baseline characteristics. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models.

Results: Of 66 patients with r/r MCL in SMC-LCS, 17 met the ZUMA-2 eligibility criteria; median (range) number of prior treatment lines was 3 (1-5) for brexu-cel and 2 (1-5) for ECA. In naïve comparison, both median OS and PFS were not reached (NR) for brexu-cel vs. 7.4 months for ECA, corresponding to HRs of 0.35 (95% CI 0.15-0.80) and 0.43 (0.21-0.91), respectively. After MAIC weighting, both median OS and PFS for ECA were 3.9 months, corresponding to HRs of 0.27 (95% CI 0.16-0.45) and 0.29 (0.19-0.46), respectively.

Conclusions: Brexu-cel demonstrated superior effectiveness over the conventional treatments for r/r MCL. Despite the small sample size, these findings may help to contextualize the therapeutic potential of CAR T-cell therapy in this setting.