Clinical Study on the CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Acute Lymphoblast Leukemia: A Single Center of Real World Data

Objective To evaluate the efficacy and safety of the CD19-targeted chimeric antigen receptor T-cell(CD19-CAR-T) therapy for relapsed/refractory B-cell acute lymphoblast leukemia(B-ALL). Methods The efficacy and safety of CD19-CAR-T cells(4-1BB costimulatory domain) in treatment of 34 patients with relapsed/refractory B-ALL from March 2015 to December 2019 in the Department of Hematology of Guangdong Second Province Hospital were collected analyzed retrospectively. There were 18 cases (52.9%) with high-risk cytogenetic or molecular markers, 14 cases (41.2%) with tumor load was ≥50% before transfusion, 24 cases (70.6%) with ECOG score ≥2. The number of chemotherapy courses received before transfusion was 2-15, the median number of chemotherapy courses was 5. There were 32 autogenous CAR-T cells and 2 donor-derived CAR-T cells, 11 of them received allogeneic hematopoietic stem cell transplantation (allo-HSCT) before transfusion. All were mouse CAR-T cells. Fludarabine + Cyclophosphamide (FC) regimen was used for pretreatment before transfusion, and the number of CAR-T cells was 1 ~ 13.4×10 6/kg. Results All 34 patients received CD19-targeted CAR-T cell therapy. 22 patients obtained MRD- after 1 month, CR rate was 64.7%. 20 patients maintained MRD- after 2 months, and the CR rate was 58.8%. 13 patients still maintained MRD- after 3 months, with a CR rate of 38.2%. 4 patients with recurrence presented CD19 negative recurrence. 10 patients underwent Allo-HSCT after CR acquisition, 6 of them maintained a continuous CR state, and 4 patients died after recurrence. Cytokines release syndrome (CRS) was observed in 31 patients (91.2%). Among them, there were 20 patients (64.5%) with grade 1 ~ 2, 8 patients (25.8%) with grade 3 ~ 4, and 3 patients (9.7%) with grade 5. The cytokines levels of IL-6 and IFN-γ were mainly increased in 20 (64.5%) and 18 (58.1%) patients, respectively. Common clinical adverse reactions are: fever with 32 cases (94.1%), pancytopenia with 28 cases (82.4%), chills with 17 cases (50.0%), fatigue with 26 cases (76.5%), hypotension with 27 cases (79.4%), tachycardia with 24 cases (70.6%), hypofibrinogenemia with 20 cases (58.8%), hypoproglobinemia with 27 cases (79.4%), neurotoxicity with 15 cases (44.1%), nausea with 16 cases (47.1%), vomiting with 14 cases (41.2%), hypoalbuminemia with 25 cases (73.5%), transaminase eleations with 16 cases (47.1%), electrolyte metabolic disorders with 27 cases (79.4%) , hypoxemiawith 15 cases (44.1%). Conclusion CAR-T cells therapy is a novel method for the treatment of refractory/recurrent B-ALL with CD19 antigen positive, which can make patients achieved complete remission in a short time, even achieved MRD negative, and most of the CRS appeared in the process of treatment can be controlled by treatment, but the recurrence rate is higher after 3 months later, and can appear CD19 negative relapse. Allo-HSCT as soon as possible after obtaining CR can enable some patients to obtain sustained CR.Therefore, more clinical studies are needed to explore the clinical application of CAR-T cell therapy. Currently, it is believed that bridging with allo-HSCT may be a solution to achieve sustained CR.