The earliest pivotal CAR-T trial for R/R DLBCL, utilizing CD19-targeted CAR-T with CD28 costimulatory domain. The ZUMA series has advanced to ZUMA 9 and real-world research, enrolling over 295 patients. Key findings: CD28-based CAR-T triggers rapid, severe cytokine release syndrome (CRS); 32% of patients required ICU admission for CRS. Re-administering identical CAR-T cells to partial response (PR) patients fails to boost efficacy.