CD19 CAR T-Cell Therapy in Refractory Autoimmune Hemolytic Anemia

作者：Ruonan Li, Lele Zhang, Hong Pan, Weiwang Li, Jian Ma, Lin Tian, Yucan Shen, Zhen Gao, Jingyu Zhao, Ke Huang, Liyun Li, Yu Xiao, Zhexiang Kuang, Meili Ge, Liwei Fang, Lijun Liu, Weiping Yuan, Shuo Chen, Lulu Lv, Junhong Song, Yi Feng, Haiqing Xiong, Jun Shi · 发表于：Blood · 年份：2024 · DOI：10.1182/blood-2024-202980 · 被引用次数：10 · 研究领域：CAR-T cell therapy research、T-cell and B-cell Immunology、Immune Cell Function and Interaction

CD19 chimeric antigen receptor (CAR) T-cell therapy emerged as a novel treatment in autoimmune diseases. Refractory autoimmune hemolytic anemia (rAIHA) is characterized by life-threatening hemolysis, and traditional B-cell-targeting treatments often fail to halt the disease. We hypothesize that resetting aberrant autoimmunity through deep depletion of B cells by CD19 CAR T-cell could be a potential strategy for rAIHA to achieve sustained drug-free remission (DFR). Refractory AIHA patients who had failed at least three lines of therapies were enrolled in a compassionate-use CD19 CAR T-cell program (n = 5) and phase I clinical trial (NCT06231368) (n = 3) to evaluate the safety and efficacy. Patients received a single dose infusion of autologous CD19 CAR T-cell 1×106 cells/kg (compassionate use) and 0.5×106 cells/kg (phase I clinical trial, dose 1) respectively after preconditioning with fludarabine (25 mg/m²/day on days -5 to -3) and cyclophosphamide (1.0 g/m²/day on day -3). Safety assessments included cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic and non-hematologic toxicities were assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Efficacy was evaluated based on hemoglobin levels and biochemical markers of hemolysis. Single-cell RNA sequencing (scRNA-seq) and single-cell V(D)J sequencing were performed to monitor the process of B cell reconstitution in bone marrow (BM) and p...