Management of cytokine release syndrome related to CAR-T cell therapy
Management of cytokine release syndrome related to CAR-T cell therapy
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DOI：
10.1007/s11684-019-0714-8
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发表时间：
2019-10-01
影响因子：
8.1
通讯作者：
He, Aili
中科院分区：
文献类型：
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作者：
Chen, Hongli;Wang, Fangxia;He, Aili
嵌合抗原受体T（CAR-T）细胞疗法是一种新型细胞免疫疗法，广泛用于治疗血液恶性肿瘤，包括急性白血病、淋巴瘤和多发性骨髓瘤。尽管其临床效果显著，但这种疗法具有不可低估的副作用。细胞因子释放综合征（CRS）是临床上最重要和可能危及生命的毒性之一。该综合征是一种全身性免疫风暴，涉及由激活的免疫细胞释放的大量细胞因子。这种现象会造成多系统损害，有时甚至死亡。在这项研究中，我们报告了1例复发性和难治性多发性骨髓瘤患者和3例急性淋巴细胞白血病患者在CAR-T治疗期间发生CRS的管理。针对持续高热、休克、急性呼吸衰竭、CRS毒性迅速恶化的患者，应根据毒性分级和临床表现，尽早应用抗IL-6受体抗体托珠单抗。此外，低剂量地塞米松（5-10 mg/天）用于对托珠单抗无应答的难治性CRS。CRS相关毒性的有效管理将为癌症患者带来额外的生存机会并改善生活质量。
Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.