A retrospective comparison of allogenic and autologous chimeric antigen receptor T cell therapy targeting CD19 in patients with relapsed/refractory acute lymphoblastic leukemia

• Published in: Bone marrow transplantation (Basingstoke) 2019-08, Vol.54 (8), p.1208-1217
• Main Authors: Hu, Yongxian, Wang, Jiasheng, Wei, Guoqing, Yu, Jian, Luo, Yi, Shi, Jimin, Wu, Wenjun, Zhao, Kui, Xiao, Lei, Zhang, Yanlei, Wu, Zhao, Xu, Huijun, Chang, Alex Hongsheng, Huang, He
• Format: Article
• Language: English
• Subjects: 42/109; 631/67/1059/2325; 692/699/1541/1990/283/2125; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Antigens; Autografts; Biological effects; Bone marrow; Care and treatment; CD19 antigen; Cell Biology; Chimeric antigen receptors; Collection; Graft-versus-host reaction; Hematology; Hematopoietic stem cells; Internal Medicine; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Peripheral blood mononuclear cells; Public Health; Risk factors; Stem cell transplantation; Stem Cells; Subgroups; T cell receptors; T cells; Transplantation
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-018-0403-2

The source of CAR T cells can be autologous (autoCAR) or allogeneic (alloCAR). The latter is seen in patients with a history of allogeneic hematopoietic stem cell transplantation, and can be either donor-derived (DD-alloCAR) or recipient-derived (RD-alloCAR). While autoCAR is activated by CAR only, alloCAR receives activation signals from both T-cell receptor (TCR) and CAR. As a result, the biological differences could impact clinical outcomes. We retrospectively reviewed 31 patients: 17 received autoCAR, 11 received RD-alloCAR, and 3 received DD-alloCAR. After a median follow-up of 9 months, CR rate was 88.2% (95% CI 63.6–98.5%) in autoCAR and 100% (95% CI 71.5–100%) in RD-alloCAR. The median peak expansion in the autoCAR was significantly higher than the RD-alloCAR group ( p  = 0.007). RD-alloCAR group had significantly less patients with severe CRS (Grade ≥ 3) than the autoCAR group ( p  = 0.049). Acute graft-versus-host disease (GVHD) occurred in 2 (18.2%) of RD-alloCAR patients and 1 (33.3%) of DD-alloCAR patients. Univariate subgroup analysis of alloCAR group showed the presence of cGVHD at the time of T-cell collection was significantly associated with less than 6-month relapses ( p  = 0.022). RD-alloCAR patients with or without cGVHD at PBMC collection did not differ regarding the peak CAR T-cell expansion, CRS grades and OS.