| ObjectiveTo analyze the prognostic factors of patients with relapsed/refractory(R/R)B-cell acute lymphoblastic leukemia(B-ALL),to compare the therapeutic effect of conventional chemotherapy and immuno-targeted therapy(CD19 CAR-T cell and CD3CD19 specific double monoclonal antibody)in patients with R/R B-ALL,and to analyze the factors influencing the short-term and long-term efficacy of CAR-T cells.Methods1.The clinical data of 309 patients with R/R B-ALL in our hospital from January2008 to July 2020 were analyzed retrospectively.The factors affecting the prognosis of patients with R/R B-ALL were studied by analyzing the gender,age,white blood cells at first diagnosis,the proportion of bone marrow primordial lymphocytes at first diagnosis,chromosome,mutant gene and fusion gene.2.212 patients with R/R B-ALL who were treated after relapse were divided into the chemotherapy group(145 cases),the anti-CD19 CAR-T cell group(59 cases)and the CD3CD19 specific double monoclonal antibody group(8 cases)according to the treatment choice.The difference in the complete response(CR)rate,overall survival(OS)and progression free survival(PFS)between chemotherapy,anti CD19 CAR-T cells and CD3CD19 specific double monoclonal antibody was compared and analyzed.3.The factors influencing the short-term and long-term efficacy of CAR-T cells and the treatment-related adverse reactions were analyzed in 59 patients treated with anti-CD19 CAR-T cells.Results1.A total of 309 patients with R/R B-ALL were collected,with the median age of 19(range: 1～72)years,the 3-year OS rate of 36.5% and the 3-year PFS rate of18.7%.Univariate analysis showed that positive E2A-PBX1,age≥30 years old,central nervous system invasion at the beginning of treatment,positive MLL-AF4 were the prognostic factors of OS and PFS in patients with R/R B-ALL(P<0.05).Allogeneic hematopoietic stem cell transplantation(allo-HSCT)could significantly prolonged the OS(P=0.000).Multivariate analysis showed that IKZF1 mutation(P=0.036)and positive E2A-PBX1 fusion gene(P=0.015)were independent adverse prognostic factors,while allo-HSCT was the independent prognostic factor(P=0.031).Age≥30 years old(P=0.000),positive E2A-PBX1 fusion gene(P=0.000),positive MLL-AF4 fusion gene(P=0.000),and central nervous system invasion at the beginning of treatment(P=0.019)were independent adverse prognostic factors of PFS.2.The CR rate of R/R B-ALL patients treated with anti-CD19 CAR-T cells was80.4%,that of patients treated with CD3CD19 specific double monoclonal antibody was 62.5%,and that of patients treated with chemotherapy was 38.6%.There was significant difference in CR rate among the three methods(P=0.000).The CR rate in CAR-T cells group was significantly higher than that in chemotherapy group(P=0.000).The CR rate of CD3CD19 double monoclonal antibody group was lower than that of CAR-T cell group and higher than that of chemotherapy group,but there was no significant difference.3.The 1-year OS rate of CAR-T cells was 41.5%,which was significantly higher than that of chemotherapy group(10.3%,P<0.0001).The 1-year PFS rate of CAR-T cells(30.1%)was also significantly higher than that of chemotherapy group(9.7%)(P<0.0001).The 1-year OS rate of patients with bridging allo-HSCT after CR treatment by CAR-T cells was 83.3%,which was higher than that of patients without allo-HSCT(31.7%,P=0.0268).The 1-year PFS rate of patients with allo-HSCT was81.5%,which was higher than that of patients without allo-HSCT(12.9%,P=0.0008).By analyzing the factors affecting the survival of patients after CAR-T cell therapy,it was found that bridging allo-HSCT after CAR-T cells was an independent prognostic factor affecting the OS and PFS(P<0.05).4.The 1-year OS rate of patients treated with CD3CD19 specific double monoclonal antibody was 14.3%,which was higher than that of chemotherapy group(10.3%)(P=0.0178).The 1-year PFS rate(14.6%)was also higher than that of chemotherapy group(9.7%)(P=0.0465).The 1-year OS rate and PFS rate of patients with bridging allo-HSCT were 33.3%,which was higher than that of patients without allo-HSCT(0%)(P<0.05).5.The incidence of cytokine release syndrome(CRS)in R/R B-ALL patients treated with anti-CD19CAR-T cells was 98.1%.Grade 3～4,grade 2,grade 1CRS were experienced by 30.2%,9.4%,58.5%.Only 3 patients(37.5%)with CD3CD19 specific double monoclonal antibody developed CRS,all of which were grade 1.Conclusion1.Among R/R B-ALL patients,age ≥30 years old,positive E2A-PBX1,positive MLL-AF4,and central nervous system invasion at the beginning of treatment significantly shorten the PFS of patients.IKZF1 mutation and positive E2A-PBX1 significantly shorten the OS of patients,while allo-HSCT significantly prolong the OS of patients.2.The curative effect of anti-CD19 CAR-T cells on patients with R/R B-ALL is significantly better than that of traditional chemotherapy.The OS and PFS of patients treated with CAR-T cells and CD3CD19 double monoclonal antibody are longer than those treated with chemotherapy.After treatment,bridging allo-HSCT can significantly improve the survival of patients.The incidence of severe CRS treated with CAR-T cells is significantly higher than that treated with CD3CD19 double monoclonal antibody. |
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