Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial

Author:

Wang Tianyi1ORCID,Tang Yanjing1,Cai Jiaoyang1ORCID,Wan Xinyu1ORCID,Hu Shaoyan2ORCID,Lu Xiaoxi3ORCID,Xie Zhiwei4,Qiao Xiaohong5,Jiang Hui6,Shao Jingbo6,Yang Fan2,Ren Hong7,Cao Qing8,Qian Juan7,Zhang Jian7,An Kang1,Wang Jianmin1,Luo Chengjuan1,Liang Huanhuan1,Miao Yan1,Ma Yani1,Wang Xiang1,Ding Lixia1,Song Lili1,He Hailong2,Shi Wenhua2ORCID,Xiao Peifang2,Yang Xiaomin1,Yang Jing1,Li Wenjie1,Zhu Yiping3,Wang Ningling4,Gu Longjun1,Chen Qimin9,Tang Jingyan1,Yang Jun J.10ORCID,Cheng Cheng11,Leung Wing12ORCID,Chen Jing1,Lu Jun2ORCID,Li Benshang1,Pui Ching-Hon13ORCID

Affiliation:

1. Department of Hematology/Oncology, National Health Committee Key Laboratory of Pediatric Hematology & Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

2. Department of Hematology/Oncology, Children's Hospital of Soochow University, Suzhou, China

3. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China

4. Department of Pediatrics, Anhui Medical University Second Affiliated Hospital, Anhui, China

5. Department of Pediatrics, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China

6. Department of Hematology/Oncology, Shanghai Children's Hospital, Shanghai, China

7. Department of Pediatric Intensive Care Unit, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

8. Department of Infectious Diseases, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

9. Department of Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

10. Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN

11. Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN

12. Department of Pediatrics, University of Hong Kong, Hong Kong SAR, China

13. Departments of Oncology, Pathology, and Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN

Abstract

PURPOSE We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19/CD22+, one CD19/CD22, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients ( P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse. [Media: see text]

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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