早期使用tocilizumab预防和治疗嵌合抗原受体T细胞(CAR-T)治疗弥漫性大b细胞淋巴瘤的疗效优于急性淋巴细胞白血病

Chengxin Luan, Haixia Wang, Junjie Zhou, Zhangbiao Long, Xin Chen, Xiaowen Chen, Jing Ni, Zhengqi Huang, Ruixiang Xia, Jian Ge
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引用次数: 0

摘要

背景托奇利珠单抗是一种行之有效的治疗嵌合抗原受体T细胞(CAR-T)治疗后细胞因子释放综合征(CRS)的策略。然而,据报道,托西利珠单抗缓解CRS的效率各不相同,突出了肿瘤类型和给药时间等影响因素。目的本研究的目的是通过早期使用托西利珠单抗预防和治疗CRS来确定弥漫性大B细胞淋巴瘤(DLBCL)和急性淋巴细胞白血病(ALL)的不同疗效。方法通过回顾性总结我们机构针对CD19的CAR-T临床试验的经验,分析11例病例:5例DLBCL和6例ALL。比较两组患者的特征、CRS信息和临床结果。3例患者接受托西利珠单抗预处理进行预防,其余患者在CRS诊断时接受托西利珠单抗治疗。结果CRS发生率81.8%(9/11),3级及以上CRS发生率55.6%(5/9)。两组患者的特征、CAR-T和CRS特征相似。然而,与ALL组相比,DLBCL组tocilizumab对CRS的疗效要好得多(80%对16.7%,P​=​0.08)。结论尽管统计数据不显著,可能是由于病例库较小,并且不可避免地存在偏差,但我们的分析表明,在CRS的预防和治疗中,早期使用托西利珠单抗对DLBCL比ALL更有效。提出了一种针对DLBCL和ALL的CRS治疗算法,该算法可以扩展到其他局部或系统性恶性肿瘤,并值得进一步研究。
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Improved efficacy with early tocilizumab in the prophylaxis and treatment of cytokine release syndrome of chimeric antigen receptor T cell (CAR-T) therapy for diffuse large B-cell lymphoma than acute lymphoblastic leukemia

Background

Tocilizumab is a well-practiced strategy to manage cytokine release syndrome (CRS) after chimeric antigen receptor T cell (CAR-T) therapy. However, varied efficiency in CRS mitigation by tocilizumab has been reported to highlight affecting variables such as tumor types and timing of the administration.

Objective

The objective of this study is to identify different curative effect between diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL) by early use of tocilizumab for prophylaxis and treatment of CRS.

Methods

By retrospectively summarizing our institution's experience with a CAR-T clinical trial targeting CD19, 11 cases were analyzed: 5 DLBCL, and 6 ALL. The two groups were compared with patient characteristics, CRS information and clinical outcomes. 3 patients were pretreated with tocilizumab for prophylaxis and the rest were treated with tocilizumab at CRS diagnosis.

Results

CRS occurred in 81.8% of patients (9/11), grade 3 or higher occurred in 55.6% of the CRS patients (5/9). The two group were similar in patient characteristics, CAR-T and CRS profile. However, tocilizumab produced much better efficacy against CRS in DLBCL group compared with ALL group (80% versus 16.7%, P ​= ​0.08).

Conclusions

Despite the statistical was non-significant, possibly due to small case pool and bias was unavoidable, our analysis suggested that early use of tocilizumab was more effective for DLBCL than ALL in the prophylaxis and treatment of CRS. A treatment algorithm for management of CRS with regard to DLBCL and ALL is proposed, which may extend to other local or systemic malignancies and warrant further investigation.

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