| Objective(s):CD19 CAR-T cell immunotherapy has achieved considerable efficacy in diffuse large B-cell lymphoma,but most of them have no response to treatment or relapse after remission.Ineffective treatment and recurrence have become a major challenge for CD19 CAR-T cell therapy.The efficacy of CAR-T cell therapy is related to many factors such as patients themselves,tumor biological characteristics,CAR-T design and so on.T cell dominated autoimmune state is an important factor affecting the clinical efficacy of CAR-T,but there are few relevant reports.Therefore,this study analyzed and explored the levels of peripheral blood T cell subsets in DLBCL patients before and after CD19 CAR-T cell therapy,and analyzed its effect on the efficacy of CAR-T cell therapy.Methods:According to the inclusion and exclusion criteria,Peripheral blood T cell subsets(CD4+ T cells,CD8+ T cells,CD4/CD8 ratio,absolute value of T cells,Helper T cells(Th)absolute value,Suppressor T Cell(Ts)absolute value,Regulatory T Cell(Treg),naive T Cell(naive T Cell,Tnaive),Effective Memory T Cell(Tem),Central Memory T Cell(Tcm))were collected from 36 DLBCL patients who successfully received CAR T cell immunotherapy in our hospital from October 2019 to January2022.The differences of peripheral blood T cell immune status before and 1 week after CD19 CAR-T cell infusion and its relationship with the efficacy and adverse reactions of CAR-T cell therapy were analyzed.The Receiver Operating Characteristic was used to calculate the Area Under Curve and the best cut-off value of T cell subsets so that can explore the T cell subsets which be able to predict the efficacy of CAR-T cell therapy and the related prognostic factors.Results:(1)Of the 36 DLBCL patients treated with CD19 CAR T cells,there were 22 males(61.1%)and 14 females(38.9%)with a median age of 48.5(15-68)years old.77.8%had received ≥2 lines of therapy in the past.94.4%(34/37)of patients had advanced disease before receiving CD19 CAR T infusion,and 16(44.4%)of patients had ECOG score ≥2.The median follow-up time was 25.7 months(95%CI 18.9-32.4 months).Overall Objective Remission Rate(ORR)and Progress Free Survival(PFS)rate were41.7% and 4.867 months(95%CI 1.705-8.028 months),respectively.The median Overall Ourvival(OS)has not been reached.(2)After infusion of CD19 CAR-T cells,the proportion of CD4+T cells and CD4/CD8 ratio in peripheral blood of DLBCL patients were significantly lower than those before infusion,while the proportion of CD8+T cells,the absolute value of T cells and the absolute value of Ts cells were significantly increased.The levels of CD4+T cells and CD4/CD8 in non-objective response group were significantly lower than those in objective response group(29.20%±31.20% vs.55.95%±32.85%,0.75±1.72 vs.1.80±2.51).All the above differences were statistically significant(p < 0.05).(3)The optimal cut-off values of CD4+T cell ratio and CD4/CD8 ratio before infusion were 38.9% and 1.24,respectively.Compared with the corresponding lower group,the ORR and median PFS of the group with higher CD4+T cells before infusion and the group with higher CD4/CD8 were higher(57.1% vs.14.3%,9.9 months vs.1.8months;61.5% vs.13.3%,9.9 months vs.1.9 months).Interestingly,the higher CD4/CD8 group was different from the corresponding lower group in terms of gender,and the above results were statistically significant(p < 0.05).(4)The incidence of cytokine release syndrome(CRS)was 55.6%,no grade 3 or higher CRS occurred,and no severe adverse reactions led to death.The proportion of Tcm cells in CRS group was higher than that in non-CRS group(45.70%±35.25% vs.24.65%±15.40%),and the difference was statistically significant(p=0.005).The most common adverse reaction was coagulation dysfunction,with an incidence of 38.9%(14/36).The absolute counts of T cells and Ts cells in the impaired coagulation function group were higher than those in the normal coagulation function group(74.00±342.00 vs.38.00±195.50,54.00±134.00 vs.12.00±127.00),and the differences were statistically significant(p < 0.05).(5)There were no significant differences in the proportion and absolute value of T cell subsets after infusion among different efficacy groups,CRS group and coagulation dysfunction group(p > 0.05).(6)Multivariate Cox proportional risk model showed that higher CD4/CD8 ratio before transfusion was an independent protective factor for patients with PFS(p=0.038).Eastern Cooperative Oncology Group Performance Status(ECOG PS)score ≥2 was an independent adverse factor affecting patients’ PFS(p=0.004).Conclusion(s):1.There are differences in peripheral blood T cell subsets in DLBCL patients before and after receiving CD19 CAR-T cell therapy,which may be related to the efficacy.2.CD4+T cells and CD4/CD8 ratio in peripheral blood of patients before infusion were related to treatment response.3.The occurrence of CRS may be related to the pre-infusion Tcm cells.4.A higher CD4/CD8 ratio in peripheral blood before infusion and ECOG PS≥2 may be independent adverse factor for PFS. |
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