ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells
ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells
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DOI：
10.1016/j.bbmt.2018.12.758
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发表时间：
2019-04-01
影响因子：
4.3
通讯作者：
Neelapu, Sattva S.
中科院分区：
文献类型：
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作者：
Lee, Daniel W.;Santomasso, Bianca D.;Neelapu, Sattva S.
嵌合抗原受体（CAR）T细胞疗法正迅速成为血液恶性肿瘤最有前途的疗法之一。两种CAR T产品最近在美国和欧洲获批用于治疗25岁以下复发性或难治性B细胞急性淋巴细胞白血病患者和/或成人大B细胞淋巴瘤患者。更多的CAR T产品以及其他免疫疗法，包括通过激活免疫效应细胞发挥作用的各种基于免疫细胞和双特异性抗体的方法，正在临床开发用于血液和实体瘤恶性肿瘤。这些疗法与细胞因子释放综合征（CRS）和神经毒性的独特毒性相关。这些毒性的评估和分级在临床试验和机构之间存在很大差异，因此难以比较不同产品的安全性，并阻碍了制定管理这些毒性的最佳策略的能力。此外，这些分级系统的某些方面在跨中心实施时可能具有挑战性。因此，为了协调CRS和神经毒性的定义和分级系统，来自该领域各个方面的专家于2018年6月20日和21日在弗吉尼亚州阿灵顿举行的美国移植和细胞治疗学会（ASTCT;前身为美国血液和骨髓移植学会，ASBMT）支持的会议上举行了会议。在这里，我们报告了该小组的共识建议，并提出了CRS和神经毒性的新定义和分级，这些定义和分级是客观的，易于应用，并最终更准确地对这些毒性的严重程度进行分类。其目标是为CRS和免疫效应细胞治疗相关的神经毒性提供统一的共识分级系统，用于临床试验和批准后的临床环境。(C)2018年美国血液和骨髓移植协会。
Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment of patients up to age 25 years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bispecific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Transplantation and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow Transplantation, ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting. (C) 2018 American Society for Blood and Marrow Transplantation.