Chimeric antigen receptor T-cell therapy is superior to standard of care as second-line therapy for large B-cell lymphoma: A systematic review and meta-analysis.

Treatment with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is considered standard of care (SOC) second-line treatment for relapsed or refractory large B-cell lymphoma (LBCL). However, outcomes remain suboptimal. A systematic review and meta-analysis of randomised controlled trials comparing efficacy and safety of SOC versus chimeric antigen receptor T-cell (CAR-T) therapy as second-line for patients with LBCL refractory or relapsing within 12 months. Outcomes included overall survival (OS), event-free survival (EFS), overall response rate (ORR) and safety. Three trials published in 2021 (involving 865 participants) fulfilled the eligibility criteria. EFS as well as OS were significantly improved with CAR-T therapy as compared to SOC, hazard ratio (HR) 0.57 (95% confidence interval [CI] 0.49-0.68) and HR 0.77 (95% CI 0.60-0.98) respectively. CAR-T therapy was associated with significantly better ORR, relative risk (RR) 1.55 (95% CI 1.12-2.13, p = 0.001). The risk of Grade III/IV adverse event was comparable between the two arms, RR 1.03 (95% CI 0.93-1.14). In summary, CAR-T therapy has superior outcomes as compared to SOC in patients with LBCL refractory or relapsing within 12 months, without excess of toxicity. Longer follow-up is needed to confirm these results and determine the optimal sequencing of CAR-T therapy in the management of LBCL.