Evidence of long‐lasting anti‐CD19 activity of engrafted CD19 chimeric antigen receptor–modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia
| Autor: | Jianqiang Li, Min Ba, Xiaoli Wu, Futian Ma, Yizhuo Wang, Huan Du, Fan Xuan, Jianmin Luo, Qinglong Wang, Ying Liu, Lin Wang, Jin-Yuan Ho |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Cyclophosphamide T-Lymphocytes Antigens CD19 Receptors Antigen T-Cell Immunotherapy Adoptive Gastroenterology CAR‐T Cell therapy 03 medical and health sciences 0302 clinical medicine Recurrence Original Research Articles Internal medicine medicine Humans Original Research Article Child Receptors Chimeric Antigen CD19 chimeric antigen receptor business.industry Hematology General Medicine Precursor Cell Lymphoblastic Leukemia-Lymphoma Prognosis medicine.disease Minimal residual disease B‐ALL Chimeric antigen receptor Fludarabine Leukemia Cytokine release syndrome Treatment Outcome medicine.anatomical_structure Oncology Child Preschool 030220 oncology & carcinogenesis Female Bone marrow business 030215 immunology medicine.drug |
| Zdroj: | Hematological Oncology |
| ISSN: | 1099-1069 0278-0232 |
| DOI: | 10.1002/hon.2672 |
| Popis: | Ninety percent of relapse/refractory B‐cell acute lymphatic leukemia (R/R B‐ALL) patients can achieve complete remission (CR) after CD19‐targeting chimeric antigen receptor T (CAR‐T) cell therapy. However, around 50% of them relapse in 1 year. Persistent CAR‐T cell engraftment is considered as the key to remain durable remission. Here, we initiated a phase I study to treat 10 pediatric B‐ALL patients using a CD19‐targeted second generation CAR with a 4‐1BB intracellular costimulatory domain. All patients received a standard fludarabine and cyclophosphamide (FC) preconditioning regiment, followed by a CAR‐T infusion with a median number of 0.5 (0.3‐1.58) × 106 CAR+ T cells/kg. The pretreatment tumor burdens were high with a median bone marrow (BM) blasts percentage of 59.2% (7.31%‐86.2%), excluding one patient only with brain infiltration of leukemia cells (0% BM blasts). The initial CR rate was 80% (n = 8/10). Four patients (40%) experienced serious (grade > 2) cytokine release syndrome (CRS) and three patients (30%) with obvious neurotoxicity. Monthly assessments of CD19+ minimal residual disease (MRD) and CAR‐T engraftment demonstrated the anti‐CD19 activity of long‐term engrafted CAR‐T cell clones in one patient for more than 2 years. |
| Databáze: | OpenAIRE |
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