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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.
Baseline Serum Inflammatory Proteins Predict Poor CAR T Outcomes in Diffuse Large B-cell Lymphoma.
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未经标记:接受CD19嵌合抗原受体(CAR)T细胞治疗的弥漫性大B细胞淋巴瘤(DLBCL)患者中,有一部分临床结局较差。我们报告了146例接受axicabtagene ciloleucel治疗的DLBCL患者中与严重免疫介导毒性及较差临床反应相关的血清蛋白。我们基于淋巴细胞清除前的C反应蛋白(CRP)和铁蛋白,开发了一种简单的分层方法,将患者分为低危、中危和高危组。我们观察到,高危类别的患者更可能发生3级毒性,并且总生存期和无进展生存期更差。我们试图通过两个独立的国际队列验证我们的发现,结果表明被归类为低危的患者具有极好的疗效和安全性结局。基于在淋巴细胞清除性化疗前可获得的常规且易于检测的实验室检查,这种简单的风险分层可以为CAR-T 细胞治疗的患者选择提供信息。意义:CAR-T 细胞治疗改变了复发/难治性血液恶性肿瘤患者的治疗模式。尽管疗效令人鼓舞,但一部分患者的临床结局较差。我们表明,使用淋巴细胞清除前CRP和铁蛋白的简单临床适用模型可以识别出结局不良高风险的患者。本文收录于本期精选文章,第80页。
UNLABELLED: A subset of patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 chimeric antigen receptor (CAR) T-cell therapy have poor clinical outcomes.
We report serum proteins associated with severe immune-mediated toxicities and inferior clinical responses in 146 patients with DLBCL treated with axicabtagene ciloleucel.
We develop a simple stratification based on pre-lymphodepletion C reactive protein (CRP) and ferritin to classify patients into low-, intermediate-, and high-risk groups.
We observe that patients in the high-risk category were more likely to develop grade 3 toxicities and had inferior overall and progression-free survival.
We sought to validate our findings with two independent international cohorts demonstrating that patients classified as low-risk have excellent efficacy and safety outcomes. Based on routine and readily available laboratory tests that can be obtained prior to lymphodepleting chemotherapy, this simple risk stratification can inform patient selection for CAR T-cell therapy.
SIGNIFICANCE: CAR T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have poor clinical outcomes.
We show that a simple clinically applicable model using pre-lymphodepletion CRP and ferritin can identify patients at high risk of poor outcomes. This article is featured in Selected Articles from This Issue, p. 80.
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