P367: long-term outcomes of adults with relapsed or refractory b-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in zuma-3 by age, prior therapies, and subsequent transplant

Background: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the US for adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and in the EU for adults ≥26 years of age with R/R B-ALL based on positive results of ZUMA-3. After 3 years of 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 months in all treated patients (N=55) and 38.9 months in patients with CR (n=31; Shah et al. EU CAR T 2023. Abstract 34). Aims: Here, we report 3-year outcomes by age, number of prior therapies, prior blinatumomab, and subsequent allogeneic stem cell transplant (alloSCT). Methods: Patients (≥18 y) had R/R B-ALL and received a single 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 months (range, 32.7-44.6). The CR/CRi rate (95% CI) was 67% (35-90) for patients <26 years (n=12) and 72% (56-85) for patients ≥26 years (n=43). The median (95% CI) OS was 28.6 months (0.6-not estimable [NE]) for patients <26 years and 34.1 months (15.9-NE) for patients ≥26 years. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 92% of patients <26 years and in 88% of patients ≥26 years. For patients with 1 prior therapy (n=10), the CR/CRi rate was 90% (95% CI, 55-100) and for patients 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 months (14.2-38.9), respectively. The incidence of Grade ≥3 TRAEs was 90% for patients with 1 prior therapy and 89% for patients with ≥2 prior therapies. The CR/CRi rates (95% CI) for patients with (n=25) and without (n=30) prior blinatumomab were 60% (39-79) and 80% (61-92). The median (95% CI) OS was 14.2 months (3.2-26.0) for patients with prior blinatumomab and NR (18.6-NE) for patients without prior blinatumomab; Grade ≥3 TRAEs occurred in 80% and 97% of patients, 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 months (18.6-NE), respectively. Similar efficacy results were observed in a pooled subgroup analysis of Phase 1 and 2 patients treated at the pivotal dose (N=78), with a median follow-up of 41.6 months (range, 32.7-70.3). Summary/Conclusion: Adults with R/R B-ALL benefitted from brexu-cel, regardless of age, number of prior therapies, prior blinatumomab exposure, or subsequent alloSCT status. Survival appeared longer in patients with fewer prior therapies and in blinatumomab-naïve patients; however, small patient 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 patients who receive brexu-cel. Keywords: Hematopoietic cell transplantation, Relapsed acute lymphoblastic leukemia, CAR-T, CD19