Efficacy and safety of chimeric antigen receptor-T cells in the treatment of B cell lymphoma:a systematic review and meta-analysis

Background:Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma.Since chimeric antigen receptor T-cell(CAR-T)technology has shown high safety and results in high remission rates,we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications.Methods:We searched databases including PubMed,Embase,and Cochrane up to July 2019.Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma,measuring the response rate and complete remission rate as outcomes.Sub-group analysis was performed for age,pathological type,target antigen,co-stimulatory molecule,and conditioning chemotherapy.Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity(cytokine-releasing syndrome[CRS],neurotoxicity)as an outcome.Results:Seventeen studies were included in the systematic review and meta-analysis.It was found that CAR-T cells had good therapeutic effects in the following cases:B-cell lymphoma(patients≥65 years old);diffuse large B-cell lymphoma pathological type;patients with treatment target antigen other than CD19;patients treated with co-stimulatory molecules other than CD28,including 4-1BB+CD28 or 4-1BB;and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy.Although the CRS and neurotoxicity incidences were high,most were reversible with minimal risk of death.Conclusion:CAR-T cell treatment is safe for clinical application;however,toxicity effects should be monitored.