Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant

• Published in: Leukemia Vol. 35; no. 6; pp. 1563 - 1570
• Main Authors: Zhang, Cheng, Wang, Xiao-Qi, Zhang, Rong-Li, Liu, Fang, Wang, Yi, Yan, Zhi-Ling, Song, Yong-Ping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.06.2021; Nature Publishing Group UK
• Subjects: Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Antigen receptors, T cell; Antigens; Cancer; Care and treatment; CD19 antigen; Cell therapy; Cellular therapy; Chimeric antigen receptors; Confidence intervals; Cytokines; Development and progression; Graft-versus-host reaction; Health aspects; Leukemia; Lymphatic leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Methods; Neurotoxicity; Oncology, Experimental; Patient outcomes; Receptors; Remission; Survival; T cells; China
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/s41375-020-01056-6

Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval [CI]: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was [greater than or equal to]grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed [less than or equal to]grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed [less than or equal to]grade-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.