Background: Brexu-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the US for adults with R/R B-ALL and in the EU for adults ≥26 y with R/R B-ALL based on positive results of ZUMA-3. After 3-y follow-up in ZUMA-3, brexu-cel demonstrated an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 71% and a median overall survival (OS) of 26.0 mo in all treated pts (N = 55) and 38.9 mo in pts with CR (n = 31; Shah et al. EU CAR T 2023. Abstract 34). Here we report 3-y outcomes by age, prior therapies, and subsequent allogeneic stem cell transplant (alloSCT). Methods: Pts (≥18 y) had R/R B-ALL and received 1 brexu-cel infusion (1×10⁶ CAR T cells/kg) following leukapheresis and conditioning chemotherapy. The primary endpoint was overall CR/CRi rate per independent review. Post hoc subgroup analyses were exploratory, with descriptive statistics reported. Results: As of July 23, 2022, the median follow-up in Phase 2 (N = 55) was 38.8 mo (range, 32.7-44.6). The CR/CRi rate (95% CI) was 67% (35-90) for pts < 26 y (n = 12) and 72% (56-85) for pts ≥26 y (n = 43). The median (95% CI) OS was 28.6 mo (0.6-not estimable [NE]) for pts < 26 y and 34.1 mo (15.9-NE) for pts ≥26 y. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 92% of pts < 26 y and in 88% of pts ≥26 y. For pts with 1 prior therapy (n = 10), the CR/CRi rate was 90% (95% CI, 55-100) and for pts with ≥2 prior therapies (n = 45), the CR/CRi rate was 67% (95% CI, 51-80); medians (95% CI) for OS were not reached (NR; 2.1-NE) and 25.6 mo (14.2-38.9), respectively. The incidence of Grade ≥3 TRAEs was 90% for pts with 1 prior therapy and 89% for pts with ≥2 prior therapies. The CR/CRi rates (95% CI) for pts with (n = 25) and without (n = 30) prior blinatumomab (blina) were 60% (39-79) and 80% (61-92). The median (95% CI) OS was 14.2 mo (3.2-26.0) for pts with prior blina and NR (18.6-NE) for pts without prior blina; Grade ≥3 TRAEs occurred in 80% and 97% of pts, respectively. For responders (CR/CRi) who did (n = 10) or did not (n = 29) proceed to subsequent alloSCT, the median (95% CI) OS was NR (7.6-NE) and 38.9 mo (18.6-NE), respectively. Similar efficacy results were observed in a pooled subgroup analysis of Phase 1 and 2 pts treated at the pivotal dose (N = 78), with a median follow-up of 41.6 mo (range, 32.7-70.3). Conclusions: Adults with R/R B-ALL benefitted from brexu-cel, regardless of age, number of prior therapies, prior blina exposure, or subsequent alloSCT status. Survival appeared longer in pts with fewer prior therapies and in blina-naïve pts; however, small pt numbers and unmatched baseline characteristics limit interpretation of these results. Additional studies are needed to determine the impact of prior therapies and/or subsequent alloSCT on outcomes of pts who receive brexu-cel. Clinical trial information: NCT02614066.