Anti-CD19 CAR-T cell therapy in relapsed/refractory t(8;21) acute myeloid leukemia with aberrant CD19 expression

Xiaomin Zhang¹LiXin Wang²Jingqiao Qiao²Shuhong Wang²Lijun Wang²Lian Liu²Jiading Qin²Ziren Chen²Wenfa Huang²Yuanyuan Zheng²Huixin Peng²Junhui Mei²Hongxin Wang²Chuan Yu³Yisheng Li^3*Li Yu^2*

• ¹International Cancer Center, Shenzhen University, Shenzhen, China
• ²Department of Hematology and Oncology, Shenzhen University General Hospital, Shenzhen, China
• ³Shenzhen Haoshi Biotechnology Co., Ltd, Shenzhen University-Haoshi Cell Therapy Institute, Shenzhen, China

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. It’s well-known that co-expression of target antigens on hematopoietic stem cells, such as CD33 and CD123, is a major challenge of CAR-T cell therapy in AML. 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. Despite the satisfactory efficacy of CD19 CAR-T cell therapy in B-cell malignancies, there are few studies investigating the efficacy and safety of CD19 CAR-T cell therapy in AML with aberrant CD19 expression at present. Thus, 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. In the present study, 3 R/R t(8;21) AML patients with aberrant CD19 expression were enrolled, and 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. 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.