Frontiers in immunology · 2025
Anti-CD19 CAR-T cell therapy in relapsed/refractory t(8;21) acute myeloid leukemia with aberrant CD19 expression.
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Zhang Xiaomin, Wang Lixin, Qiao Jingqiao, Wang Shuhong, Wang Lijun, Liu Lian, Qin Jiading, Chen Ziren, Huang Wenfa, Zheng Yuanyuan, Peng Huixin, Mei Junhui, Wang Hongxin, Yu Chuan, Li Yisheng, Yu Li
Аннотация
BACKGROUND: T (8; 21) acute myeloid leukemia (AML) is a special type of acute leukemia, and exhibits a heterogeneous prognosis, with a long-term relapse rate of about 40%. Once t(8; 21) AML patients experience relapse, they have an extremely poor prognosis, with a 5-year overall survival rate of less than 15%. Therefore, it is crucial to develop effective strategies to improve the prognosis of relapsed/refractory (R/R) t(8; 21) AML. CD19 is a specific B-cell surface marker, but it is aberrantly expressed in 50-80 % of t(8; 21) AML patients. CAR-T cells targeting aberrant cell-surface antigens could induce the depletion of tumor cells without the destruction of hematopoiesis. Therefore, CD19 might be a promising target for CAR-T cell therapy in R/R t(8; 21) AML with aberrant CD19 expression. The present study is aimed to explore the efficacy and safety of CD19 CAR-T cell therapy in R/R t(8;21) AML with aberrant CD19 expression.
METHODS: In the present study, 3 R/R t(8;21) AML patients with aberrant CD19 expression were enrolled. After lymphodepleting chemotherapy, 3 patients received autologous CAR-T cell infusion at a dose of 1.0 × 10^6 cells/kg, 2.0 × 10^6 cells/kg, and 2.0 × 10^6 cells/kg, respectively.
RESULTS: They all achieved CD19 negativity approximately half a month after CD19 CAR-T cell infusion. These indicate CD19 CAR-T cell therapy is effective in R/R t(8;21) AML with aberrant CD19 expression. However, patient 1 and patient 2 rapidly relapsed within 3 months after CD19 CAR-T cell therapy. Subsequently, patient 1 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fortunately, patient 1 achieved mCR 2 months after allo-HSCT.
CONCLUSION: Considering the short-term remission of CD19 CAR-T cell therapy in R/R t(8;21) AML, allo-HSCT might be performed as soon as possible to consolidate the efficacy of CAR-T cell therapy and reduce the risk of relapse.
METHODS: In the present study, 3 R/R t(8;21) AML patients with aberrant CD19 expression were enrolled. After lymphodepleting chemotherapy, 3 patients received autologous CAR-T cell infusion at a dose of 1.0 × 10^6 cells/kg, 2.0 × 10^6 cells/kg, and 2.0 × 10^6 cells/kg, respectively.
RESULTS: They all achieved CD19 negativity approximately half a month after CD19 CAR-T cell infusion. These indicate CD19 CAR-T cell therapy is effective in R/R t(8;21) AML with aberrant CD19 expression. However, patient 1 and patient 2 rapidly relapsed within 3 months after CD19 CAR-T cell therapy. Subsequently, patient 1 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fortunately, patient 1 achieved mCR 2 months after allo-HSCT.
CONCLUSION: Considering the short-term remission of CD19 CAR-T cell therapy in R/R t(8;21) AML, allo-HSCT might be performed as soon as possible to consolidate the efficacy of CAR-T cell therapy and reduce the risk of relapse.