Durable Molecular Remission in a Lymphoid BP-CML Patient Harboring T315I Mutation Treated with Anti-CD19 CAR-T Therapy

Lu Zhou,1 Huiping Shi,2 Wenyu Shi,1 Li Yang,1 Yaping Zhang,1 Mengqi Xu,1 Xiufang Chen,1 Yanv Zhu,1 Hui Mu,1 Xiaochun Wan,3 Zhonghua Yang,3 Ying Zeng,3,* Hong Liu1,* 1Hematology Department, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China; 2Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA; 3Shenzhen Bin De Bio Tech Co. Lid, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong LiuHematology Department, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, Jiangsu 226001, People’s Republic of ChinaEmail Hongliu63@126.comYing ZengShenzhen Bin De Bio Tech Co. Lid, Rich Industrial Park, Shenzhen 518055, People’s Republic of ChinaEmail ying.zeng@bindebio.comAbstract: Despite the prominent effects of BCR-ABL tyrosine kinase inhibitors (TKI) therapy in patients with chronic phase-chronic myeloid leukemia (CP-CML) and thus low incidence of blastic transformation, blast phase (BP)-CML remains a major therapeutic challenge in the TKI era. The “gatekeeper” mutation T315I in BCR-ABL1 kinase, which often coupled with a poor prognosis, is quite common and resistant to all TKIs except for ponatinib. The occurrence of T315I mutation in BP-CML makes the situation more complex. Anti-CD19 chimeric antigen receptor T cell (CAR-T) technology is a new immunotherapy which has significantly improved the efficacy of B cell hematologic malignances. Here we report a lymphoid BP-CML patient harboring T315I mutation who achieved complete molecular remission and returned to chronic phase by anti-CD19 CAR-T therapy. Our study provides a new therapeutic strategy for patients in BP-CML.Keywords: anti-CD19 CAR-T, BP-CML, BCR-ABL1, T315I