Efficacy And Safety Of CD19 Chimeric Antigen Receptor T Cells Therapy In Patients With Relapsed Acute B Lymphoblastic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation

BackgroundAllo-HSCT is the primary treatment of ALL,which has made great progress in the past decades.However,recurrence still occurs frequently after transplantation,which is the main cause of death after allo-HSCT,but there is no satisfactory rescue plan.The advent of CAR T therapy has revolutionized the treatment of R/R hematologic malignancies.Due to the specific expression of CD19 on the surface of B lymphocytes,CAR-T cells targeting CD19 have been widely used in the treatment of B-ALL,especially for B-ALL patients with recurrence after transplantation,providing a glimmer of hope for this population.Since CD19 CAR T cells(Kymriah)were approved by the FDA for the treatment of r/r B-ALL,there has been increasing research on CAR T cells for r/r BALL.In recent years,relevant studies have suggested that retrobridging allo-HSCT may improve event-free survival(EFS)and leukemia free survival(LFS)of patients treated with CAR T cells for r/r B-ALL.However,there are few reports on the efficacy and safety of CAR T cell therapy in patients who relapsed after receiving allo-HSCT.ObjectiveTo evaluate the clinical efficacy and adverse reaction of all-HSCT before CD19 CD19CAR-T therapy in patients with B-ALL.MethodsWe collected the data of r/r B-ALL patients treated with homologous CD19 CAR-T in our hospital from June 2015 to June 2019.According to whether HSCT was performed before treatment,the patients were divided into transplantation group and nontransplantation group.The ORR、RFS 、OSand general adverse events were compared between the two groups.Results(1)A total of 47 r/r B-ALL patients treated with homo CD19 CAR T cells were screened,9 of whom had received allo-HSCT before treatment.(2)Complete Remission/Complete Remission with Incomplete Hematologic recovery was achieved in 8 of 9 patients in the transplant group after CD19 CAR-T treatment Recovery,CR/CRi),30 of 38 patients in the non-transplant group achieved CR/CRi after CD19 CAR T treatment,and there was no statistical difference in ORR between the two groups(88.9% vs.78.9%,P=0.667).After excluding CAR T cell therapy,the median RFS of the remaining 9 graft and 28non-graft patients were 386 days vs.95 days,respectively(Wilcoxon test,P=0.028;Log-Rank test,P=0.231);The 1-year RFS rates were 62.5% vs.20%(P = 0.068).The median OS was 852 days vs.222 days(Wilcoxon test,P=0.049;Log-Rank test,P=0.186);The one-year OS rate was 77.8% vs.35.7%(P=0.052).(3)At 4 weeks after CAR T infusion,8 of the 9 Graft patients had CRS,2 of them had grade 3,and none of the 9 patients had neurotoxicity or GVHD.Compared with 38 non-graft patients,There was no statistical difference in the incidence of general adverse events and special adverse reactions.ConclusionB-ALL patients who had previously received allo-HSCT prior to CD19 CAR T cell therapy may have improved survival without increased adverse reactions.