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

• DOI: 10.1038/s41375-020-01056-6
• Publication Date: 2020-10-19T14:07:20Z
• Authors: Cheng Zhang; Xiao-Qi Wang; Rong-Li Zhang; Fang Liu; Yi Wang; Zhi-Ling Yan; Yong-Ping Song; Ting Yang; Ping Li; Zhen Wang; Ying-Ying Ma; Lei Gao; Yao Liu; Li Gao; Pei-Yan Kong; Jun Liu; Xu Tan; Jiang F. Zhong; Yu-Qing Chen; Ai-Bin Liang; Jin-Hua Ren; Zhen-Yu Li; Jiang Cao; Quan-Li Gao; Jian Zhou; Ying Gao; Ding Zhang; Fang-Yi Fan; Ming-Zhe Han; Robert Peter Gale; Xi Zhang
• Keywords: Adult; Male; Adolescent; Antigens, CD19; Immunotherapy, Adoptive; Article; 03 medical and health sciences; 0302 clinical medicine; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Humans; Child; Aged; Retrospective Studies; Receptors, Chimeric Antigen; Hematopoietic Stem Cell Transplantation; Middle Aged; Prognosis; Tissue Donors; 3. Good health; Survival Rate; Child, Preschool; Female; Neoplasm Recurrence, Local; Follow-Up Studies

AbstractSafety 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 ≥grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed ≤grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed ≤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.