Five-year follow-up of patients with relapsed/refractory mantle cell lymphoma treated with anti-CD19 CAR T-cell therapy in ZUMA-2, Cohorts 1 and 2

Abstract Background Treatment with brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated a high objective response rate (93%) and complete response rate (67%) in 60 patients with relapsed/refractory mantle cell lymphoma (R/R MCL) treated in the pivotal ZUMA-2 Cohort 1 study. Subsequently, brexu-cel was approved in the United States and European Union for the treatment of adults with R/R MCL (after ≥ 2 prior therapies in the European Union). Here we report 5-year outcomes from the pivotal ZUMA-2 Cohort 1 study ( N = 68), as well as two previously unpublished ZUMA-2 data sets, long-term outcomes in 10 patients who received axi-cel in Cohort 1 and in 14 patients who received a lower dose of brexu-cel in Cohort 2. Methods The primary endpoint for all cohorts of ZUMA-2 was objective response rate. Key secondary endpoints included duration of response (DOR), overall survival (OS), and safety. Patients could transition to a long-term follow-up study after 24 months for monitoring of survival and select adverse events possibly related to brexu-cel. Patients in Cohort 1 received a single infusion of 2 × 10 6 anti-CD19 CAR T cells/kg (axi-cel or brexu-cel). Patients in Cohort 2 received 0.5 × 10 6 anti-CD19 CAR T cells/kg (brexu-cel). Results Median follow-up for the pivotal cohort ( N = 68) was 67.8 months (range, 58.2–88.6) with a median DOR of 36.5 months ( n = 60), per investigator review. Median OS was 46.5 months (95% CI, 24.5–60.2; N = 68) and was 60.2 months (95% CI, 42.8-not estimable) in patients with complete response ( n = 46). The 5-year incidence of cumulative relapse-related and non-relapse–related mortality was 40% (24/60) and 22% (13/60) in responders, respectively. Descriptive outcomes for axi-cel–treated patients ( N = 10) and Cohort 2 ( N = 14) are reported herein. No Grade 5 cytokine-release syndrome or neurologic events, subsequent T-cell malignancies, or new safety signals were reported in any patient. Conclusions Patients in ZUMA-2 continued to have durable responses after 5 years of follow-up with predictable long-term safety, supporting the continued use of brexu-cel in R/R MCL. Interpretations of outcomes in axi-cel–treated patients and Cohort 2 are not feasible due to small patient numbers and unmatched baseline characteristics. Trial registration NCT02601313 and NCT05041309.