[Analysis on poor efficacy factors in the treatment of recurrent/refractory B-cell lymphoma with CD19 CAR-T cells]

Objective: To investigate the factors influencing the efficacy of CD19 chimeric antigen receptor T (CAR-T) cells in the treatment of patients with relapsed refractory B cell lymphoma and to provide evidence for further improvement of CAR-T efficacy. Methods: A total of 34 patients with relapsed and refractory B-cell lymphoma were recruited from the Department of Hematology of Tianjin First Central Hospital from February 2017 to January 2019. All patients received CD19 CAR-T cell therapy. These patients were evaluated for efficacy, factors with poor efficacyand adverse effects. Results: The overall response rate was 58.8% (20/34) and the complete remission rate was 41.2% (14/34) after infusion of CD19 CAR-T cells in 34 patients with relapsed refractory B cell lymphoma. According to the efficacy of CAR-T cells, patients were divided into two groups, 20 in the effective group and 14 in the poorly effective group. The median am ount of CD19 CAR-T cell infusions in these two groups were 8.6 (5.0-12.7)×10(6)/kg and 9.7 (5.8-15.0) × 10(6)/kg, respectively, and the difference was not statistically significant (P=0.654). The percentage of CD19 CAR-T cells in the effective group and the poorly treated group was 10.28% (3.92%-44.16%) and 4.05% (0.92%-28.63%), respectively.The effective group had a higher proportion of CAR-T cells than the poorly treated group, but the difference was not statistically significant (P=0.371).The presence of massive mass was an unfavorable factor affecting the efficacy of CD19 CAR-T cells and the difference was statistically significant (P=0.001). Logistic regression multivariate analysis showed that the characteristics of massive tumors were still independent prognostic factors for poor efficacy of CD19 CAR-T cells (P=0.005, OR=0.039). Of all 34 patients, there were 70.6% (24/34) who showed varying degrees of adverse reactions after the infusion of CD19 CAR-T cells, mainly cytokines release syndrome (CRS). The median time of occurrence of fever was on the third day after infusion (0-11th) day. 16 patients were with grade 1 CRS, 7 with grade 2, and 1 with grade 3. After glucocorticoids and support treatment, they all showed improvements. Conclusions: CD19 CAR-T cell therapy has achieved a certain effect in CD19(+)B cell lymphoma, but has poor efficacy on some patients. Large mass tumors may be an adverse factors to CAR-T cell treatment.