e22002 Background: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies have improved outcomes for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). Direct comparisons between approved products—axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)—remain limited, complicating evidence-based selection in clinical practice. Methods: We performed a PRISMA-compliant systematic review and meta-analysis of randomized clinical trials and real-world studies (through March 2025) evaluating long-term efficacy and safety of commercially available CD19 CAR-T therapies in adults with R/R DLBCL. PubMed, Embase, Cochrane Library, and conference abstracts were searched. Pooled estimates were calculated using random-effects models. Results: Twenty-five studies (4,067 patients; median follow-up 24.6 months) were included. The pooled overall response rate (ORR) was 74% (95% CI, 69–79%), with a complete response (CR) rate of 52% (95% CI, 43–60%). Axi-cel showed the highest ORR (77%; 95% CI, 72–81%) and CR rate (47%; 95% CI, 45–50%). Pooled 1-year progression-free survival (PFS) was 43% (95% CI, 37–49%), and 1-year overall survival (OS) was 66% (95% CI, 59–73%). Safety profiles differed significantly: axi-cel was associated with the highest incidence of immune effector cell-associated neurotoxicity syndrome (ICANS; 34%), while liso-cel had the lowest (9%; 95% CI, 6–13%). Rates of cytokine release syndrome were comparable across products. Conclusions: All approved CD19 CAR-T therapies provide meaningful clinical benefit in R/R DLBCL, but with distinct efficacy–toxicity profiles. These findings support a personalized approach to product selection, integrating patient comorbidities, disease aggressiveness, and institutional experience. Pooled efficacy outcomes of CD19 CAR-T therapies. Outcome Axi-cel (95% CI) Tisa-cel (95% CI) Liso-cel (95% CI) Overall Pooled (95% CI) Overall response rate (ORR), % 77% 72–81 54% 45–64 74% 68–79 74% 69–79 Complete response (CR), % 47% 45–50 42% 38–46 49% 46–51 52% 43–60 1-year PFS, % 45% 42–47 28% 25–32 26% 23–28 43% 37–49 1-year OS, % 65%63–68 56%51–60 55%52–58 66%59–73 CI, confidence interval; ORR, overall response rate; CR, complete response; PFS, progression-free survival; OS, overall survival. Interpretation: The overall pooled estimates (right column) represent a weighted average across all included studies and patient populations. The superior ORR/CR with axi-cel and the favorable safety profile of liso-cel (see main text) underscore the need for treatment personalization.
Hamed et al. (Thu,) studied this question.