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:Impact of Chronic Kidney Disease and Acute Kidney Injury on Safety and Outcomes of CAR T-Cell Therapy in Lymphoma Patients.
CAR-T后发生CKD或AKI对术后OS和PFS无影响。
CAR-T 细胞疗法是复发/难治性侵袭性B细胞非霍奇金淋巴瘤的标准治疗。关于CAR-T治疗前存在的慢性肾脏病(CKD)以及CAR-T治疗后发生的急性肾损伤(AKI)的影响,现有数据有限,我们试图在我们的患者中对此进行评估。
在这项单中心回顾性分析中,CKD队列定义为在CAR-T治疗前评估时依据KDIGO分期,eGFR <60 mL/min/1.73 m2(3期及以上)。其余患者构成无CKD组。AKI依据CTCAEv.4定义,数据提取至CAR-T治疗后第100天。主要结局为既往存在的CKD对无进展生存期(PFS)、总生存期(OS)和不良事件的影响。此外,我们还分析了AKI对PFS和OS的影响。
共识别出32例患者,其中7例存在既往CKD。在伴或不伴CKD的患者中,中位PFS分别为8.8个月和2.9个月(p值0.78)。中位OS分别为10个月和7个月(p值0.64)。CAR-T后共有9例患者(29%)发生AKI,包括7例基线无CKD的患者。未发生AKI和发生AKI的患者中位PFS分别为3.6个月和2.8个月(p值0.84)。中位OS按相同顺序分别为10个月和3.9个月(p值0.2)。单因素分析中,基线肌酐(p值0.018)和ICANS 2级及以上(p值0.016)与发生AKI风险增加相关。
INTRODUCTION: Chimeric antigen receptor T-cell (CAR-T) therapy is standard-of-care in relapse/refractory aggressive B-cell non-Hodgkin lymphoma. There are limited data regarding the impact of pre-existing chronic kidney disease (CKD) and acute kidney injury (AKI) post CAR-T and we sought to evaluate these in our patients. METHOD: In this single center retrospective analysis CKD cohort was defined KDIGO staging with eGFR of <60 mL/min/1.73 m2 (Stage ...3) at the time of pre-CAR-T assessment. Remaining patients constituted the no CKD group. AKI was defined by CTCAEv.4 and data were abstracted through Day 100 post-CAR-T therapy. The primary outcome was impact of pre-existing CKD on progression-free survival (PFS), overall survival (OS) and adverse events. Additionally, we also analyzed the impact of AKI on PFS and OS. RESULTS: Thirty-two patients were identified with 7 having pre-existing CKD. Among the patients with or without CKD, the median PFS was 8.8 and 2.9 months respectively (pvalue 0.78). The median OS was 10 and 7 months respectively (p-value 0.64). AKI developed in a total of 9 patients (29%) post CAR-T, including 7 patients without CKD at baseline. The median PFS was 3.6 and 2.8 months for patients not developing AKI and developing AKI (p-value 0.84). Median OS in similar order was 10 and 3.9 months respectively (p-value 0.2). On univariate analysis, creatinine at baseline (p-value 0.018) and ICANS grade 2+ (p-value 0.016) were associated with an increased risk of developing AKI. CONCLUSIONS: CKD or AKI after CAR-T showed no impact on post procedure OS and PFS.
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