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1937 Tandem CD19/CD22 Dual Targets CAR-T Cells Therapy Acquires Superior CR Rate Than CD19 CAR-T Cells: A Case Controlled Study

Program: Oral and Poster Abstracts
Session: 614. Acute Lymphoblastic Leukemia: Therapy, excluding Transplantation: Poster II
Hematology Disease Topics & Pathways:
Non-Biological, Therapies
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Wei Cui1*, Xinyue Zhang2*, Haiping Dai3*, Qingya Cui1*, Baoquan Song4*, Depei Wu, MD, PhD5, Xiaowen Tang, MD, PhD1*, Jia Yin4* and Zheng Li2*

1National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China
2National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China 215006., Soochow, Jiangsu, China
3Department of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, China
4Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China
5The First Affiliated Hosp. of Soochow University, Suzhou, Jiangsu, China

Background: CD19 chimeric antigen receptor (CAR) T-cells therapy has shown unprecedented success in relapsed/refractory (r/r) ALL. Now it is recommended for the treatment of patients up to 25 years with r/r precursor B-ALL. Despite its high response rate, approximately 50% of r/r ALL patients relapsed after CD19 CAR T-cell therapy, which was mainly due to CD19 antigen loss or short persistence of CAR T-cells in vivo. CD19 and CD22 dual target CAR T-cells have demonstrated to reduce relapse post CD19 CAR T-cell therapy in limited cases. This study was designed to investigate the efficacy and safety of CD19/CD22 dual targets CAR-T cells and the correlation between that and CD19 CAR-T cells.

Methods: A novel tandem CD19/CD22 CAR-T construct with CD28 and OX40 co-stimulatory domains were administered. All patients received FC (fludarabine, 30 mg/m2, days 1-3 and cyclophosphamide, 300 mg/m2, days 1-3) based regimen chemotherapy pre-infusion. Median infusion dose of CAR-T cells was 1(0.5-2.5) *107 cells/kg. All the patients accepted the bone marrow examination 28 days post CAR-T infusion.

We conducted a retrospective, case controlled study analysis at the First Hospital of Soochow University. Every patient with active disease treated with CD19/CD22 CAR-T cells therapy was paired with one control subject who received CD19 CAR-T cells from January 2017 to September 2019. We matched the control group to prevent bias according to: (1) bone marrow blast before CAR-T infusion; (2) extramedullary involvement; (3) cytogenetic risk groups according to NCCN guideline; (4) transplantation status pre-infusion.

Results: From 2017 Oct to 2020 Jul, 36 patients were enrolled into the clinical trial (NCT: 03614858). Patients who accepted more than 4 previous treatments account for 58.3% and 8 patients received stem cell transplantation pre-infusion. Bone marrow blasts 40.75 (0~94.5)%. After tandem CD19/CD22 CAR-T infusion, all patients achieved completely remission (CR) and minimal residual disease negative (MRD-) CR rate is 77.8%. The 6-month OS rate is 88.36% and 12-month OS rate is 70.6%. The 6-month LFS rate is 88.072% and the 12-month LFS rate is 69.216%. CAR-T bridging HSCT (25/36) obviously improves the 1-year LFS rate compared with non-transplantation group (11/36) (82.309% vs 31.169%, p=0.0135). All the side effects were mild and can be relieved through support treatments. 8 out of 36 patients developed with grade 3~4 CRS. 2 patients had HLH but soon relieved through low dose steroids.

28 out of 36 patients who accepted dual targets CAR-T cells didn’t get complete remission before infusion. Therefore, 28 patients were enrolled in the CD19 CAR-T group. There are no significant differences between two groups at baseline. The CR rate was higher in CD19/CD22 group than that in CD19 group(100% vs 53.57%, p=0.000), so was MRD-CR rate(71.43% vs 42.86%,p=0.000). In survival analysis, 6 month overall survival rate of CD19/CD22 group was 69.276% while CD19 group was 53.571%. Of 28 patients who received dual target treatment, 7 patents relapsed while 4 relapsed out of 15 CR patients in CD19 group.

Conclusions: The tandem CD19/22 dual CAR-T cell therapy is a safe and high efficacy treatment for R/R ALL patients. Our study demonstrated that dual targets CAR-T cells acquires higher CR rate than CD19 CAR-T cells. It is possible that multi-targeted CAR-T cell therapy may overcome this resistance mechanism and improve clinical outcomes.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH