Safety And Efficacy Of CAR-T Cells In Patients With Refractory Or Relapsed B-cell Lymphoma

Purpose To investigate the safety and clinical efficacy of third generation CD19 single target,CD20 single target or CD19 combined with CD20 double target chimeric antigen receptor T cell(CAR-T)in the treatment of relapsed and refractory B-cell lymphoma.Methods 15 patients with recurrent or refractory B-cell lymphoma and CD19/CD20 on the tumor surface cured in our hospital from June 2015 to December 2018 were selected.The subtypes included 2 patient with diffuse large B-cell lymphoma,7patients with B lymphoblastic lymphoma,one patient with Burkitt lymphoma,one patient with high-level B-cell lymphoma,one patient with large B-cell lymphoma into plasmablastic lymphoma,one patient with chronic lymphocytic leukemia into diffuse large B-cell lymphoma,and one patient with chronic myeloid leukemia into B-cell lymphoblastic lymphoma.Autologous peripheral blood T lymphocyte was collected for transfection,cultivation and gene modification in vitro to gain T cells of chimeric antigen receptor with tumor specificity.After preprocessing for 5-7d,CD19/CD20CAR-T cells with autonomous specificity were infused to patients.Patients' vital signs and CAR-T treatment security of cell factor level were evaluated.Focus changes and other clinical indexes relating to lymphoma before and after infusion were compared to evaluate clinical curative effect of curing lymphoma for autonomous CAR-T cells.Result 1)Among the 15 patients,1 could not be evaluated because of the progress of the disease combined with radiotherapy and chemotherapy.The remaining 14 patients couldbe evaluated were treated with CD19 single target CAR-T cells.Three patients achieved complete remission and two patients achieved partial remission.The objective response rate was 35.7%,and the complete remission rate was 21.4%.One patient who received single-target CAR-T cell therapy was ineffective.CD19 combined with CD20double-target CAR-T cells were reinfused to achieve complete remission and maintain curative effect for more than 2 years.2)In 14 patients to be evaluated,12patients(85.7%)had level 1-2 cytokine release syndrome,including 10 patients of level1 and 2 patients of level 2.Symptomatic support or glucocorticoid was used for treatment without untoward effects.All patients had no neurotoxicity relating to CAR-T cell treatment.12 patients(85.7%)had reduction of immune globulin level after infusing CAR-T cells.Conclusion CAR-T therapy provided a safe and effective treatment scheme for recurrent or refractory B-cell lymphoma.The controlled untoward effect of CRS and reduction of immune globulin would happen in the treatment process.For patients who failed to respond to single-target therapy,dual-target CAR-T cell therapy may be tried,which is expected to achieve complete remission.