Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02129, USA; email:
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Annu Rev Med. 2021 Jan 27;72:365-382. doi: 10.1146/annurev-med-061119-015600. Epub 2020 Aug 10.
Adoptive transfer of T cells modified with chimeric antigen receptors (CAR-T cells) has changed the therapeutic landscape of hematological malignancies, particularly for acute lymphoblastic leukemia and large B cell lymphoma, where two different CAR-T products are now considered standard of care. Furthermore, intense research efforts are under way to expand the clinical application of CAR-T cell therapy for the benefit of patients suffering from other types of cancers. Nevertheless, CAR-T cell treatment is associated with toxicities such as cytokine release syndrome, which can range in severity from mild flu-like symptoms to life-threatening vasodilatory shock, and a neurological syndrome termed ICANS (immune effector cell-associated neurotoxicity syndrome), which can also range in severity from a temporary cognitive deficit lasting only a few hours to lethal cerebral edema. In this review, we provide an in-depth discussion of different types of CAR-T cell-associated toxicities, including an overview of clinical presentation and grading, pathophysiology, and treatment options. We also address future perspectives and opportunities, with a special focus on hematological malignancies.
嵌合抗原受体 (CAR-T) 修饰的 T 细胞过继转移改变了血液系统恶性肿瘤的治疗格局，特别是对于急性淋巴细胞白血病和大 B 细胞淋巴瘤，目前已有两种不同的 CAR-T 产品被认为是标准治疗方法。此外，人们正在积极努力扩大 CAR-T 细胞疗法的临床应用，使患有其他类型癌症的患者受益。然而，CAR-T 细胞治疗与细胞因子释放综合征等毒性相关，其严重程度从轻度流感样症状到危及生命的血管舒张性休克不等，还会出现一种称为 ICANS（免疫效应细胞相关神经毒性综合征）的神经系统综合征，其严重程度也从仅持续数小时的短暂认知障碍到致命性脑水肿不等。在这篇综述中，我们深入讨论了不同类型的 CAR-T 细胞相关毒性，包括对临床表现和分级、病理生理学和治疗选择的概述。我们还讨论了未来的前景和机遇，特别关注血液系统恶性肿瘤。
