Clinical Study Of CD19 Prime CAR T Cell For Relapsed/refractory Acute B-lymphocytic Leukemia

Objective:To investigate the safety and efficacy of the new Prime chimeric antigen receptor(CAR)T-cell therapy for relapsed/refractory B-acute lymphocytic leukemia(r/r B-ALL).and follow-up treatment after CAR T relapse,to provide a basis for optimizing and improving CAR T cell therapy.Methods:The clinical data of 20 patients with r/r B-ALL treated with Prime CAR T in our hospital from September 2021 to October 2022 were included in this study.To determine the safety and efficacy of CAR T cell therapy and to monitor the treatment-related complications cytokine releasing syndrome(CRS),cell-related encephalopathy syndrome(CRES),overall Patients who relapsed after CAR T cell therapy were treated with allogeneic hematopoietic stem cell transplantation to clarify the effectiveness of the treatment and to observe the related complications and prognosis.Results:1.20 patients with r/r B-ALL were included in the study;8 were male and 12 were female,median age was 28(6-70)years,7 patients had first recurrence,12 patients had≥2 recurrences,and 1 was primary refractory.2.The mean tumor load of enrolled patients was as high as 56.6%.16 patients(80%)had CRS,with a 10%incidence of grade 3-5.2 patients(10%)had CRES,with a 5%incidence of grade 3-4.3.At a median dose of 2.5(1.16-18.2)×10~5/kg of CAR T cell infusion,an objective remission rate of 100%was achieved,with 19 cases(95%),achieving MRD-negative complete remission(CR).As of the time of the last follow-up,the median OS was 279 days,the one-year OS was 95%,the median DFS was 225 days,and the one-year DFS was 55%.4.3 patients who had MRD conversion(BCR or fusion gene monitoring)after CAR T cell therapy were subsequently treated with allogeneic HSCT,and all 3patients achieved complete remission after transplantation(two patients with fusion gene conversion and one with BCR conversion)and did not develop grade III-IV GVHD.Conclusion(s):1.compared with traditional CAR T,the new Prime CAR T can shorten the in vitro culture time,improve the affinity and survival of CAR T,while increasing the CR rate and cure rate and reducing the relapse rate,which has high clinical value.2.Prime CAR T can reduce the dose of cell infusion and decrease the incidence of CRS and CRES,which is a safe and effective treatment strategy.3.For relapsed patients after CAR T treatment,taking bridging allogeneic hematopoietic stem cell transplantation is expected to improve the long-term survival rate of patients;for patients who relapse again after transplantation,antibody-based drugs,targeted therapy and secondary CAR T treatment can be used.