Assessment of Early Intervention Strategies for Management of Cytokine Release Syndrome and Neurologic Events after Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients with Relapsed or Refractory Mantle Cell Lymphoma (R/R MCL) in ZUMA-2

Introduction:Brexu-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the United States for the treatment of adults with R/R MCL and in the European Union for adults with R/R MCL after ≥2 prior therapies, including a Bruton tyrosine kinase inhibitor (BTKi). In the Phase 2 ZUMA-2 study, with a median follow-up of 35.6 months, brexu-cel showed an objective response rate of 91%, a median duration of response of 28.2 months, and a median overall survival of 46.6 months with a manageable safety profile in treated patients (pts) with R/R MCL (N=68). Grade (Gr) ≥3 infections, cytokine release syndrome (CRS), and neurologic events (NEs) occurred in 37%, 15%, and 31% of pts, respectively (Wang et al. J Clin Oncol. 2023). In August 2018, CRS and NE management strategies for ZUMA-2 were updated to initiate treatment of these adverse events earlier at the onset of Gr 1 events to improve safety outcomes. Here, we report 4-yr safety outcomes for pts in ZUMA-2 by initial and updated CRS and NE management strategies.