Safety and efficacy of co-administration of CD19 and CD22 CAR-T cells in children with B-ALL relapse after CD19 CAR-T therapy

• Published in: Journal of translational medicine Vol. 21; no. 1; p. 213
• Main Authors: Li, Wenjie, Ding, Lixia, Shi, Wenhua, Wan, Xinyu, Yang, Xiaomin, Yang, Jing, Wang, Tianyi, Song, Lili, Wang, Xiang, Ma, Yani, Luo, Chengjuan, Tang, Jingyan, Gu, Longjun, Chen, Jing, Lu, Jun, Tang, Yanjing, Li, Benshang
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.03.2023; BioMed Central; BMC
• Subjects: Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Allografts; Antigens; Antigens, CD19; B-ALL; Bone marrow; Care and treatment; CD19 antigen; CD19/CD22 CAR-T; CD22 antigen; Chemotherapy; Child; Chimeric antigen receptors; Clinical trials; Co-administration; Cytokines; Diagnosis; Disease; Flow cytometry; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Lymphoma, B-Cell; Medical prognosis; Minimal residual disease; Patients; Pediatrics; Peripheral blood; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - etiology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Receptors, Chimeric Antigen; Recurrence; Remission; Remission (Medicine); Second CAR-T; Sialic Acid Binding Ig-like Lectin 2; Stem cell transplantation; T-Lymphocytes; Toxicity; Transplantation; Tumor necrosis factor-TNF; Lithuania; United States > US; Germany; B-ALL; Co-administration; CD19/CD22 CAR-T; Second CAR-T
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-04019-4

CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable efficacy in treating relapsed or refractory pediatric B-lineage acute lymphoblastic leukemia (B-ALL). However, poor results are obtained when the same product is reused in patients who relapse after CAR-T. Therefore, there is a need to explore the safety and efficacy of co-administration of CD19- and CD22-targeted CAR-T as a salvage second CAR-T therapy (CART2) in B-ALL patients who relapse after their first CD19 CAR-T treatment (CART1). In this study, we recruited five patients who relapsed after CD19-targeted CAR-T. CD19- and CD22-CAR lentivirus-transfected T cells were cultured separately and mixed before infusion in an approximate ratio of 1:1. The total dose range of CD19 and CD22 CAR-T was 4.3 × 10 -1.5 × 10 /kg. Throughout the trial, we evaluated the patients' clinical responses, side effects, and the expansion and persistence of CAR-T cells. After CART2, all five patients had minimal residual disease (MRD)-negative complete remission (CR). The 6- and 12-month overall survival (OS) rates were 100%. The median follow-up time was 26.3 months. Three of the five patients bridged to consolidated allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CART2 and remained in MRD-negative CR at the cut-off time. In patient No. 3 (pt03), CAR-T cells were still detected in the peripheral blood (PB) at 347 days post-CART2. Cytokine release syndrome (CRS) only occurred with a grade of ≤ 2, and no patients experienced symptoms of neurologic toxicity during CART2. Mixed infusion of CD19- and CD22-targeted CAR-T cells is a safe and effective regimen for children with B-ALL who relapse after prior CD19-targeted CAR-T therapy. Salvage CART2 provides an opportunity for bridging to transplantation and long-term survival. Chinese Clinical Trial Registry, ChiCTR2000032211. Retrospectively registered: April 23, 2020.