ZUMA-2 phase II 5-year follow-up: Brexu-cel in R/R MCL

Five-year follow-up results from Cohort 1 and Cohort 2 of the phase II ZUMA-2 trial (NCT02601313), evaluating brexucabtagene autoleucel (brexu-cel) in adults with relapsed/refractory (R/R) mantle cell lymphoma (MCL), were published in the Journal of Hematology & Oncology by Muñoz et al. In Cohort 1, patients received 2 × 10⁶ anti-CD19 chimeric antigen receptor (CAR) T-cells/kg brexu-cel (n = 68), while patients in Cohort 2 received 0.5 × 10⁶ anti-CD19 CAR T-cells/kg (n = 14). The primary endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DoR), best objective response (BOR), and investigator-assessed ORR.

Key data: The median DoR was 36.5 months (95% confidence interval [CI], 17.7–48.9) in Cohort 1. Among patients with a complete response (CR), median DoR was 46.7 months. The median progression-free survival (PFS) and overall survival (OS) were 25.3 months and 46.5 months, respectively. In Cohort 2, the overall response rate was 93%, with a median DoR of 57.5 months (95% CI, 4.7–not estimable [NE]). The median PFS and OS were 29.5 months and not reached (NR), respectively. The estimated cumulative incidence of non-relapse mortality (NRM) at 5 years was 19.0% in Cohort 1. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 15% and 31% of patients in Cohort 1, and 14% and 43% in Cohort 2, respectively. No Grade 5 CRS, neurologic events, subsequent T-cell malignancies, or new safety signals were observed.

Key learning: Brexu-cel demonstrated durable long-term responses and survival with a predictable safety profile after 5 years, supporting its continued use in heavily pretreated patients with R/R MCL.