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681 Safety and Efficacy of Bicistronic CD19/CD22 CAR T Cell Therapy in Childhood B Cell Acute Lymphoblastic Leukemia

Program: Oral and Poster Abstracts
Type: Oral
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: B Cell-directed CAR T Cell Therapies for ALL and for Autoimmunity
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Sunday, December 8, 2024: 5:00 PM

Xinyu Wan1*, Wenjie Li1*, Jiaoyang Cai2, Xiaomin Yang1*, Liu Yang1*, Jing Yang1*, Tianyi Wang1*, Yue Li3*, Zichao Zhou1*, Xiaoxi Lu4*, Zhiwei Xie3*, Jingbo Shao5*, Meng Su1*, Jing Zhang1*, Juan Qian1*, Kang An1*, Chengjuan Luo1*, Lixia Ding6*, Lili Song1*, Wenhua Shi1*, Jun Lu7*, Cheng Cheng8*, Yanjing Tang6*, Xuefeng Luo, MD9*, Jingyu Li9,10*, Jian Hua, MD9,10*, Benshang Li, MD, PhD6*, Hua Zhang, MD, PhD9,10* and Ching-Hon Pui, MD11

1Department of Hematology/Oncology, Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Shanghai Children’s Medical Center, Shanghai, China
2Key Laboratory of Pediatric Hematology & Oncology of the Ministry of Health of China, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
3Department of Pediatrics, Anhui Medical University Second Affiliated Hospital, Hefei, Anhui, China
4West China Second University Hospital, Sichuan University, Chengdu, China
5Department of Hematology/Oncology, Shanghai Children’s Hospital, Shanghai, China
6Department of Hematology/Oncology, Key Laboratory of Pediatric Hematology & Oncology Ministry of Health, Shanghai Children's Medical Center, Shanghai, China
7Department of Hematology/Oncology, Children's Hospital of Soochow University, Suzhou, China
8Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN
9SPH Biotherapeutics (Shanghai), Limited, Shanghai, China
10SPH Biotherapeutics (HK), Limited, Hong Kong, Hong Kong
11Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN

Background: Our previous study on co-administration of CD19- and CD22-CAR T cell therapy demonstrated durable remission in children with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL) (Wang et al. J Clin Oncol 2023; 41:1670-83). To further improve outcomes, we developed a bicistronic CD19/CD22 CAR (B019) aimed at enhancing event-free survival (EFS) and overall survival (OS) in the treatment of relapsed or refractory childhood B-ALL. The primary objectives were to assess EFS, OS, and safety of bicistronic CD19/CD22 CAR T cell in the treatment of patients with relapsed or refractory B-ALL with or without consolidative allogeneic stem cell transplant after CAR-T therapy.

Methods: In this investigator-initiated trial using a new bicistronic construct, we enrolled 318 evaluable patients aged ≤ 18 years between January 2022 and April 2024. Median follow-up for patients who were alive at the time of analysis was 13.9 months (IQR 9.0-22.4). Throughout the trial, we evaluated the patients' clinical responses, side effects, and the expansion and persistence of CAR-T cells.

Results: The response rate (CR+CRi) was 99.1% among the 318 patients, all of whom were MRD negative (<0.01%). The 12-month EFS and OS rates for 267 patients with isolated or combined hematologic relapse were 72.4% and 91.4% respectively. Consolidative transplantation was associated with favorable outcomes and was performed in 37 of 267 patients (13.9%). The 12-month EFS was 86.0% for those who received transplantation versus 71.4% for those who did not (p=0.04). However, regarding OS, transplantation did not provide a significant benefit, with 12-month OS rates of 94.2% for transplanted patients and 92.2% for non-transplanted patients (p=0.86). Among the 230 patients who did not undergo transplantation after CAR-T cell therapy, 69 patients relapsed with different loss of the antigens (45 CD19+/CD22+, 23 CD19-/CD22+, and 1 CD19-/CD22-). Most were treated with a second salvaged bicistronic CD19/CD22 CAR-T cell therapy, achieving complete remission again in 35 of 36 (97.2%) CD19+/CD22+ patients and 14 of 21 (66.7%) CD19-/CD22+ patients. Among the 49 patients who achieved complete remission, 42 (85.7%%) were still alive in remission for (1.0 to 22.1 months), 30 of whom received consolidative transplantation. For the 20 patients with isolated testicular relapse, the 12-month EFS and OS rates were 84.7% and 100.0%, respectively. For the 29 patients with isolated CNS relapse, the 12-month EFS and OS rates were 71.0% and 96.2%, respectively. Cytokine release syndrome developed in all patients, with grade III-IV CRS occurring in 48.7% (155 patients), resulting in two deaths. CAR T-cell neurotoxicity was observed in 52 patients (16.4%).

Conclusions: Bicistronic CD19/CD22-targeted CAR-T cell therapy is a safe and effective regimen which achieved durable remission in children with relapsed or refractory B-ALL, including those with isolated or combined extramedullary relapse.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH