Efficacy and safety of chimeric antigen receptor T-cell therapy in relapsed/refractory large B-cell lymphoma: a systematic review and meta-analysis

Background: Individuals diagnosed with relapsed or refractory large B-cell lymphoma (R/R LBCL) typically exhibit a dismal prognosis when treated with conventional therapeutic modalities. CD19—targeted chimeric antigen receptor T (CAR-T) cell therapy has brought about a paradigm shift in the treatment paradigm of this disease. Nevertheless, a comprehensive assessment of the efficacy and safety profiles of diverse CAR-T products (e.g., axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)) is imperative. Objective: This systematic review aims to systematically summarize and evaluate the efficacy and safety of CAR T-cell therapies for R/R LBCL through systematic review and meta-analytic approaches. Design: This is a systematic review and meta-analysis. Data sources and methods: Relevant studies were identified by systematically searching PubMed and Web of Science until November 29, 2023. Cohort studies and clinical trials were incorporated, with the inclusion of single-arm studies. CAR T-cell therapies are involved in tisa-cel, axi-cel, and liso-cel. Proportions and their 95% confidence intervals were calculated using standard meta-analytic approaches. Results: Thirty-seven studies were included in meta-analyses, liso-cel demonstrated equivalent overall survival rates (70.3%) to axi-cel (65.6%) at 12 months post-treatment, whereas tisa-cel was 48.0%. Objective response rate for liso-cel was comparable to axi-cel (79.0% vs 76.8%, p meta-regression = 0.74), both of which were notably higher than those observed for tisa-cel (58.3%, both p meta-regression < 0.05). Regarding safety assessments, liso-cel exhibited the lowest cytokine release syndrome rate at 43.0%, followed by tisa-cel at 70.9%, and axi-cel at 87.9%. However, tisa-cel had the lowest incidence of neurologic events (14.9%), in contrast to liso-cel (21.1%) and axi-cel (52.3%). Conclusion: Based on the available evidence, liso-cel has shown promising efficacy and a manageable safety profile in patients with R/R LBCL, when compared to axi-cel and tisa-cel. However, real-world data on liso-cel are limited.