Feasibility, and Efficacy of Donor-Derived cd19-Targeted Car t-Cell Therapy in Refractory/Relapsed(r/r)b-Cell Acute Lymphoblastic Leukemia (b-all) Patients

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.4-6
• Main Authors: Zhang, Xian, Yang, Junfang, Li, Wenqian, Zhang, Gailing, Su, Yunchao, Shi, Yanze, Song, Dan, Zhang, Min, He, Jiujiang, Xu, Li, Qiu, Liyuan, Lu, Xin-An, Wu, Fei, Li, Jianqiang, Chen, Dandan, Li, Xiangqun, Li, Ziyu, Li, Jingjing, Lu, Peihua
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-137299

▪ Backgrounds As CAR T-cell therapy is a highly personalized therapy, process of generating autologous CAR-T cells for each patient is complex and can still be problematic, particularly for heavily pre-treated patients and patients with significant leukemia burden. Here, we analyzed the feasibility and efficacy in 37 patients with refractory/relapsed (R/R) B-ALL who received CAR T-cells derived from related donors. Patients and Methods From April 2017 to May 2020, 37 R/R B-ALL patients with a median age of 19 years (3-61 years), were treated with second-generation CD19 CAR-T cells derived from donors. The data was aggregated from three clinical trials (www.clinicaltrials.gov NCT03173417; NCT02546739; and www.chictr.org.cn ChiCTR-ONC-17012829). Of the 37 patients, 28 were relapsed following allogenic hematopoietic stem cell transplant (allo-HSCT) and whose lymphocytes were collected from their transplant donors (3 HLA matched sibling and 25 haploidentical). For the remaining 9 patients without prior transplant, the lymphocytes were collected from HLA identical sibling donors (n=5) or haploidentical donors (n=4) because CAR-T cells manufacture from patient samples either failed (n=5) or blasts in peripheral blood were too high (>40%) to collect quality T-cells. The median CAR-T cell dose infused was 3×105/kg (1-30×105/kg). Results For the 28 patients who relapsed after prior allo-HSCT, 27 (96.4%) achieved CR within 30 days post CAR T-cell infusion, of which 25 (89.3%) were minimal residual disease (MRD) negative. Within one month following CAR T-cell therapy, graft-versus-host disease (GVHD) occurred in 3 patients including 1 with rash and 2 with diarrhea. A total of 19 of the 28 (67.9%) patients had cytokine release syndrome (CRS), including two patients (7.1%) with Grade 3-4 CRS. Four patients had CAR T-cell related neurotoxicity including 3 with Grade 3-4 events. With a medium follow up of 103 days (1-669days), the median overall survival (OS) was 169 days (1-668 days), and the median leukemia-free survival (LFS) was 158 days (1-438 days). After CAR T-cell therapy, 15 patients bridged into a second allo-HSCT and one of 15 patients (6.7%) relapsed following transplant, and two died from infection. There were 11 patients that did not receive a second transplantation, of which three patients (27.3%) relapsed, and four parents died (one due to relapse, one from arrhythmia and two from GVHD/infection). Two patients were lost to follow-up. The remaining nine pa