Efficiency and safety of autologous chimeric antigen receptor T-cells therapy used for patients with lymphoma A systematic review and meta-analysis

Background: Chimeric antigen receptor (CAR) T-cell therapy has produced promising response rates in patients with B cell malignancies. However, previous meta-analyses have demonstrated that CAR T-cell efficacy is unsatisfactory in patients with lymphoma unlike in patient with other hematological malignancies, but these studies included insufficient numbers of studies and patients with lymphoma. Furthermore, clinicians are interested in the effects of infusion dose, CAR structure, interleukin-2 (IL-2), and conditioning therapy regimen. Methods: All clinical trials administering autologous CAR T-cell therapy in lymphoma patients were searched in medical databases. A traditional meta-analysis was performed to assess the safety and efficacy of CAR T-cells in lymphoma treatment. Subgroup analysis was performed to determine the relationships between potential factors and efficacy. The best overall response rate (ORR), 6 month ORR (6m ORR), and severe cytokine release syndrome (sCRS) rate were calculated by Stata 14.0. Results: A total of 411 patients across all the studies were included. Our analysis showed a best ORR of 0.71, a 6m ORR of 0.63, and an overall CRS (grade >= 3) rate of 0.18. The subgroup analysis showed that increased response rates and reduced CRS (grade >= 3) rates were associated with a low dose of CAR T-cells. No IL-2 administration and the use of a fludarabine-containing lymphodepletion regimen led to improved efficacy, while anti-CD19 CAR T cells led to a more successful outcome than anti-CD20 CAR T cells. In addition, 2nd- and 3rd-generation CAR T cells exhibited increased effectiveness in clinical studies, and no significant effect diversity was found between the 2nd- and 3rd-generation CAR T cells. sCRS was associated with a high dose of infused CAR T cells when IL-2 and fludarabine were excluded from the positive factors for sCRS. Conclusion: CAR T cells are promising in the treatment of relapsed or refractory lymphoma. Doses lower than 10(8)/m(2), no IL-2 administration, fludarabine administration, and anti-CD19 CAR T cells were related to improved efficacy and safety.