Toxicity of Brexucabtagene Autoleucel as a Standard Therapy for Adults with Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia Open Access

• Rate of grade 3+ cytokine release syndrome (CRS) was lower than in pivotal trial; rate of grade 3+ neurotoxicity (ICANS) was similar.

• Prior allogeneic transplantation was the only factor that demonstrably reduced the odds of developing grade 3+ CRS.

Brexucabtagene autoleucel (brexu-cel) is an autologous chimeric antigen receptor T-cell (CAR-T) therapy directed to CD19 that is approved for use in adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Pivotal trial data and real-world experience (RWE) studies show high response rates, but also relatively high rates of grade 3+ cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In this RWE study, we sought to better characterize the toxicity profile of brexu-cel in adult patients with R/R B-ALL. To that end, we examined outcomes data from our RWE database for 292 adult patients treated with brexu-cel between October 2021 and June 2024. We found numerically comparable levels of grade 3+ ICANS (28.8%) to those reported on the pivotal ZUMA-3 study, but numerically lower rates of grade 3+ CRS (9.8%). Other clinically-relevant findings included 20.5% requiring intensive care unit-level care, and a rate of death by day +28 post CAR-T of 5.2%. The hazard ratio for death for those with vs. without grade 3+ CRS was 2.24 (95% confidence interval [CI], 1.27-3.94, p=0.005). Compared to those without prior allogeneic transplantation (HCT), the odds of grade 3+ CRS for those with prior HCT was 0.35; (95% CI, 0.14-0.89; p=0.03). While brexu-cel had high response rates in both the trial setting and RWE, our data suggest that severe toxicities (particularly ICANS) remain a distinct challenge with this product. Careful attention to patient selection for brexu-cel is warranted, particularly as new CAR-T agents become available in this disease space.