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:Managing side effects: guidance for use of immunotherapies in multiple myeloma.
Managing side effects: guidance for use of immunotherapies in multiple myeloma.
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CAR-T 细胞疗法和双特异性T细胞招募抗体已经改变了复发/难治性多发性骨髓瘤的治疗格局,其中B细胞成熟抗原是最常见的靶点,其他靶点也正在临床开发中。
然而,这些疗法与独特且严重的毒性相关,包括细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)、迟发性神经毒性、血细胞减少和感染。
此外,免疫效应细胞相关噬血细胞性淋巴组织细胞增多症(HLH)样综合征(IEC-HS)在CRS和HLH之间存在重叠,诊断和治疗可能具有挑战性。在这篇综述中,我们概述了用于治疗多发性骨髓瘤的新型免疫疗法相关的毒性,并描述了管理建议。这些毒性背后的病理生理学和危险因素尚未被全面了解。根据共识建议,CRS的治疗包括托珠单抗和类固醇,而ICANS的治疗包括类固醇,重症病例中使用阿那白滞素。血细胞减少和感染的管理类似于造血细胞移植后的原则,包括抗微生物预防、生长因子支持、免疫球蛋白替代和疫苗接种。相比之下,迟发性神经毒性和IEC-HS缺乏有效的治疗方法,尽管类固醇和阿那白滞素常被使用。所有这些毒性的管理都应包括广泛的鉴别诊断,以及与感染科、神经科和/或重症监护人员的多学科协作。
Chimeric antigen receptor T-cell therapy and bispecific T-cell recruiting antibodies have transformed the treatment landscape for relapsed/refractory multiple myeloma, with B-cell maturation antigen being the most common target and other targets in clinical development.
However, these therapies are associated with unique and severe toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), delayed neurotoxicity, cytopenias, and infection.
In addition, immune effector cell-associated hemophagocytic lymphohistiocytosis (HLH)-like syndrome (IEC-HS), which exhibits overlap between CRS and HLH, can be challenging to diagnose and treat. In this review, we provide an overview of toxicities associated with novel immunotherapies for treatment of multiple myeloma and describe management recommendations. The pathophysiology and risk factors behind these toxicities are not yet comprehensively understood. Based on consensus recommendations, treatment for CRS consists of tocilizumab and steroids, while treatment for ICANS includes steroids and anakinra in severe cases.
Management of cytopenias and infection is similar to post-hematopoietic cell transplantation principles with antimicrobial prophylaxis, growth factor support, immunoglobulin replacement, and vaccinations. In contrast, effective treatments for delayed neurotoxicity and IEC-HS are lacking, although steroids and anakinra are commonly used. Management of all these toxicities should include a broad differential and multidisciplinary collaboration with infectious diseases, neurology, and/or critical care providers.
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