DataSheet_1_Organ complications after CD19 CAR T-cell therapy for large B cell lymphoma: a retrospective study from the EBMT transplant complications and lymphoma working party.docx

We investigated ≥ grade 3 (CTC-AE) organ toxicities for commercial CD19 chimeric antigen receptor T cell (CAR-T cell) products in 492 patients (Axi-Cel; n = 315; Tisa-Cel; n = 177) with Large B-cell Lymphoma in the European Society for Blood and Marrow Transplantation (EBMT) CAR-T registry. The incidence of ≥ grade 3 organ toxicities during the first 100 days after CAR-T was low and the most frequent were: renal (3.0%), cardiac (2.3%), gastro-intestinal (2.3%) and hepatic (1.8%). The majority occurred within three weeks after CAR-T cell therapy. Overall survival was 83.1% [79.8-86.5; 95% CI] at 3 months and 53.5% [49-58.4; 95% CI] at one year after CAR-T. The most frequent cause of death was tumour progression (85.1%). Non-relapse mortality was 3.1% [2.3-4.1; 95% CI] at 3 months and 5.2% [4.1-6.5; 95% CI] at one year after CAR-T. The most frequent causes of non-relapse mortality were cell-therapy-related toxicities including organ toxicities (6.4% of total deaths) and infections (4.4% of total deaths). Our data demonstrates good safety in the European real-world setting.

我们针对欧洲血液与骨髓移植学会（European Society for Blood and Marrow Transplantation, EBMT）CAR-T注册库中492例弥漫大B细胞淋巴瘤患者，分析了商业化CD19嵌合抗原受体T细胞（chimeric antigen receptor T cell, CAR-T细胞）产品相关的≥3级（CTC-AE）器官毒性事件；其中接受阿基仑赛（Axi-Cel）者315例，接受替沙仑赛（Tisa-Cel）者177例。CAR-T细胞治疗后前100天内，≥3级器官毒性的发生率较低，最常见的类型为肾脏毒性（3.0%）、心脏毒性（2.3%）、胃肠道毒性（2.3%）及肝脏毒性（1.8%），绝大多数事件发生于治疗后3周内。CAR-T细胞治疗后3个月的总生存率为83.1%[95%CI：79.8~86.5]，1年总生存率为53.5%[95%CI：49~58.4]。最常见的死亡诱因为肿瘤进展（85.1%）。CAR-T细胞治疗后3个月的非复发死亡率为3.1%[95%CI：2.3~4.1]，1年非复发死亡率为5.2%[95%CI：4.1~6.5]。非复发死亡最常见的诱因包括细胞治疗相关毒性（其中器官毒性占总死亡例数的6.4%）与感染（占总死亡例数的4.4%）。本研究数据表明，在欧洲真实世界临床场景中，此类CAR-T细胞治疗具有良好的安全性。