CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cytomegaloviral Infections in Recipients of Chimeric Antigen Receptor T-Cell Therapy: An Observational Study With Focus on Oncologic Outcomes.
Cytomegaloviral Infections in Recipients of Chimeric Antigen Receptor T-Cell Therapy: An Observational Study With Focus on Oncologic Outcomes.
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需要进一步研究免疫相关标志物和开展临床试验以确定预防策略的疗效,从而理解 CS-CMVi 与 CAR-T 后死亡率的作用。
接受CAR-T 细胞治疗的B细胞淋巴瘤和急性淋巴细胞白血病(ALL)患者可能发生具有临床意义的巨细胞病毒感染(CS-CMVi)。然而,CS-CMVi的危险因素尚未明确。本研究旨在识别CS-CMVi的危险因素,以及CS-CMVi与淋巴瘤和ALL患者接受CAR-T 治疗后非复发死亡(NRM)之间的关联。
我们开展了一项单中心回顾性队列分析,纳入2018年1月至2021年2月期间接受CAR-T 治疗淋巴瘤和ALL的患者。我们收集了人口统计学、肿瘤病史、CAR-T 治疗相关并发症以及治疗后1年内感染性并发症的数据。
在230例患者中,22例(10%)发生CS-CMVi。CAR-T 治疗后1年,75例(33%)出现疾病复发,95例(41%)死亡;1年NRM为37%。Cox回归分析显示,亚洲或中东种族(校正风险比[aHR],13.71 [95%置信区间{CI},5.41-34.74])、使用类固醇治疗细胞因子释放综合征/免疫效应细胞相关神经毒性综合征(aHR,6.25 [95% CI,1.82-21.47])、CAR-T 治疗时的乳酸脱氢酶(aHR,1.09 [95% CI,1.02-1.16])以及CMV监测(aHR,6.91 [95% CI,2.77-17.25])与CS-CMVi独立相关。CS-CMVi与CAR-T 治疗后1年NRM独立相关(比值比,2.49 [95% CI,1.29-4.82])。
Patients with B-cell lymphoma and acute lymphoblastic leukemia (ALL) who receive chimeric antigen receptor T-cell (CAR-T) therapy may experience clinically significant cytomegalovirus infection (CS-CMVi). However, risk factors for CS-CMVi are not well defined. The aims of our study were to identify risk factors for CS-CMVi and the association between CS-CMVi and nonrelapse mortality (NRM) in lymphoma and ALL patients after CAR-T therapy.
We performed a retrospective single-center cohort analysis of CAR-T recipients between January 2018 and February 2021 for treatment of lymphoma and ALL. We collected data on demographics, oncologic history, CAR-T therapy-related complications, and infectious complications within 1 year of therapy.
Of 230 patients identified, 22 (10%) had CS-CMVi. At 1 year following CAR-T therapy, 75 patients (33%) developed relapsed disease and 95 (41%) died; NRM at 1 year was 37%. On Cox regression analysis, Asian or Middle Eastern race (adjusted hazard ratio [aHR], 13.71 [95% confidence interval {CI}, 5.41-34.74]), treatment of cytokine release syndrome/immune effector cell-associated neurotoxicity syndrome with steroids (aHR, 6.25 [95% CI, 1.82-21.47]), lactate dehydrogenase at time of CAR-T therapy (aHR, 1.09 [95% CI, 1.02-1.16]), and CMV surveillance (aHR, 6.91 [95% CI, 2.77-17.25]) were independently associated with CS-CMVi. CS-CMVi was independently associated with NRM at 1 year after CAR-T therapy (odds ratio, 2.49 [95% CI, 1.29-4.82]).
Further studies of immunologic correlatives and clinical trials to determine the efficacy of prophylactic strategies are needed to understand the role of CS-CMVi and post-CAR-T mortality.
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