Clinical Study Of Targeting CD19 Fourth-generation Chimeric Antigen Receptor T Cells In Treating Relapsed Or Refractory B Cell Non-hodgkin Lymphoma

ObjectiveThis study aims to evaluate the clinical efficacy and safety of CD19-targeted fourth-generation chimeric antigen receptor T cells(4SCART)in treating relapsed or refractory B-cell non-Hodgkin lymphoma,and to explore the factors that may affect these two aspects.Materials and methodsPatients were recruited into our "Clinical study of CD 19-CART cells in the treatment of relapsed and refractory B lymphocyte malignancies" according to the inclusion and exclusion criteria.(Registration number:ChiCTR-OOC-16007779).The lymphocytes of the patients were collected and used to produce anti-CD 194SCART cells.The patients were treated with fludarabine and cyclophosphamide for 3 days,and received 4SCART cells 2 days after withdrawal.Demographic and clinical characteristics,CART cell infusion data and follow-up information were collected and analyzed.The primary endpoint was the overall response rate(ORR),and the secondary endpoints included duration of response(DoR),event-free survival(EFS),overall survival(OS)and the incidence and severity of adverse events.Results1.A total of 21 patients received an infusion of 4SCART cells and were included in the efficacy analysis.The overall response rate was 67%,of which the complete response rate was 43%.In all patients,the median follow-up was 13.7 months,and the median overall survival was 23.8 months.2.The most common adverse events of grade 3 or 4 during treatment were neutropenia(76%),leukopenia(71%),and thrombocytopenia(29%).The incidence of cytokine release syndrome(CRS)was 14%,all of which were Grade 1.One patient developed grade 3 neurotoxicity.No deaths were attributed to infusion of 4SCART cells,CRS,or neurotoxicity.3.The IPI prognostic index,disease type,and remission status after CART cell treatment were associated with overall survival.ConclusionsIn this study,patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma who received 4SCART-cell therapy had high rates of durable responses and few of adverse events.