决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Late cytopenia after CD19 chimeric antigen receptor T-cell therapy in large B-cell lymphoma: a Cell Therapy Consortium analysis.
晚期血细胞减少是 CD19 CAR-T 细胞治疗后常见且具有临床意义的毒性。
CD19靶向嵌合抗原受体(CAR)T细胞治疗后30天以上出现迟发性细胞减少,是复发/难治性大B细胞淋巴瘤(R/R LBCL)患者的重要并发症,但现有数据有限且异质性较高。本多中心回顾性研究评估接受CD19 CAR-T患者迟发性细胞减少的发生率、模式、危险因素及影响。研究纳入2016年4月至2023年5月期间在细胞治疗联盟8家学术中心接受治疗的444例R/R LBCL患者。排除复发、接受新治疗、死亡或失访患者后,在具有相应数据者中,输注后1、2、3、6及12个月3级细胞减少发生率分别为47%、34%、19%、21%和11%。在307例具有完整血液学数据的患者中,103例(33.6%)于第30至100天出现符合迟发性免疫效应细胞相关血液学毒性的中性粒细胞减少。多变量分析发现,CAR-HEMATOTOX评分较高(≥2)可预测第3个月细胞减少;接受桥接化疗及阿基仑赛治疗与CAR-T后第6个月细胞减少相关。迟发性细胞减少与1年非复发死亡率较高(11%比4.4%;P=0.038)、2年PFS较差(38%比67%;P=0.035)及2年OS较差(60%比76%;P=0.016)相关。总之,迟发性细胞减少是CD19 CAR-T治疗后常见且具有临床意义的毒性。识别危险因素并持续监测,对于优化CAR-T治疗后照护及降低治疗相关死亡至关重要。
Late cytopenia ( 30 days after chimeric antigen receptor [CAR] T-cell therapy) is a significant complication after CD19-directed CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). However, available data remain limited and heterogeneous. In this retrospective multicenter study, we evaluated the incidence, patterns, risk factors, and impact of late cytopenia in patients treated with CD19 CAR T cells. A total of 444 patients with R/R LBCL treated at 8 academic centers within the Cell Therapy Consortium between April 2016 and May 2023 were included. After excluding patients with relapse, new treatment, death or lost to follow-up, grade 3 cytopenias were observed in 47%, 34%, 19%, 21%, and 11% of patients with available data at 1, 2, 3, 6, and 12 months after infusion. Among 307 patients with complete hematologic data, neutropenia consistent with late immune effector cell-associated hematotoxicity was identified in 103 patients (33.6%) between days 30 and 100. Multivariable analysis identified a high CAR-HEMATOTOX score ( 2) as a predictor of cytopenia at 3 months, whereas receipt of bridging chemotherapy and axicabtagene ciloleucel was associated with cytopenia at 6 months after CAR T-cell therapy. The presence of late cytopenia was associated with a higher 1-year nonrelapse mortality (11% vs 4.4%; P = .038), worse 2-year progression-free survival (38% vs 67%; P = .035), and worse 2-year overall survival (60% vs 76%; P = .016). In conclusion, late cytopenia is a common and clinically meaningful toxicity after CD19 CAR T-cell therapy. Recognition of risk factors and consistent monitoring are essential for optimizing post-CAR T-cell therapy care and reducing treatment-related mortality.
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