Abstract Background CD19‐directed chimeric antigen receptor (CAR)‐T‐cell therapy has emerged as a second‐line option for relapsed/refractory large B‐cell lymphoma (R/R LBCL). However, its long‐term benefits over standard of care (SOC) remain a matter of debate. Methods A systematic review and meta‐analysis was performed of three randomized controlled trials (ZUMA‐7, TRANSFORM, BELINDA) and one real‐world comparative study evaluating second‐line CAR‐T versus standard‐of‐care chemoimmunotherapy (±autologous stem cell transplantation) in adults with early R/R LBCL. Hazard ratios (HRs) and 95% CIs for overall survival (OS), event‐free survival (EFS), and progression‐free survival (PFS) were pooled. Individual patient data were reconstructed to generate pooled Kaplan‐Meier survival curves. Subgroup analyses and long‐term safety outcomes were also evaluated. Results A total of 1199 patients were included. Pooled analyses demonstrated a significant benefit of CAR‐T over SOC in OS (HR = 0.75; 95% CI, 0.62–0.92), EFS (HR = 0.51; 95% CI, 0.33–0.78), and PFS (HR = 0.47; 95% CI, 0.39–0.58). Three‐year OS and PFS estimates from reconstructed data were 53.59% and 44.08% in the CAR‐T group, compared to 41.46% and 17.82% with SOC, respectively. Subgroup analyses confirmed consistent EFS across subgroups, including age, disease subtype, and relapse status. Long‐term toxicities indicated more frequent hypogammaglobulinemia with CAR‐T cell therapy, with no excess in secondary malignancies. Conclusions Second‐line CAR‐T therapy significantly improves long‐term survival and disease control in R/R LBCL, with consistent benefit across subgroups and real‐world settings. These findings support early CAR‐T use as a standard strategy in high‐risk LBCL, while emphasizing the importance of timely delivery and long‐term monitoring.
Tang et al. (Sun,) studied this question.