嵌合抗原受体(CAR)-T细胞疗法可有效治疗难治性/复发性(r/r)血液恶性肿瘤(r/rB细胞淋巴细胞白血病,B细胞淋巴瘤,和多发性骨髓瘤)。此外,它正在探索作为实体瘤的治疗选择。截至2022年3月31日,七种用于血液系统恶性肿瘤的CAR-T疗法已在全球获得批准。虽然CAR-T疗法是许多恶性肿瘤的有效治疗方法,也会造成不良影响。细胞因子释放综合征(CRS)的发生率,CAR-T细胞输注后最常见的不良反应,高达93%。CRS,是免疫效应细胞相关神经毒性综合征(ICANS)的主要危险因素,以及心血管,血液学,肝肾,皮肤,肺,和胃肠道毒性。CRS导致的严重不良反应严重阻碍了CAR-T疗法的广泛应用。CAR-T产品最初于2017年获得批准;然而,与临床批准的药物相比,只有有限的研究调查了由于CAR-T疗法引起的不良反应.因此,我们旨在阐明机制,危险因素,诊断标准,以及与CRS并发的毒性治疗,从而为安全、有效,以及CAR-T疗法的广泛应用。
Chimeric antigen receptor (CAR)-T cell therapy is effective in the treatment of refractory/relapsed (r/r) hematological malignancies (r/r B-cell lymphoblastic leukemia, B-cell lymphoma, and multiple myeloma). In addition, it is being explored as a treatment option for solid tumors. As of 31 March 2022, seven CAR-T therapies for hematological malignancies have been approved worldwide. Although CAR-T therapy is an effective treatment for many malignancies, it also causes adverse effects. The incidence of cytokine release syndrome (CRS), the most common adverse reaction after infusion of CAR-T cells, is as high as 93%.CRS, is the leading risk factor of immune effector cell-associated neurotoxicity syndrome (ICANS), as well as cardiovascular, hematological, hepatorenal, skin, pulmonary, and gastrointestinal toxicity. Severe adverse reactions complicated by CRS severely impede the widespread application of CAR-T therapy. The CAR-T product was initially approved in 2017; however, only limited studies have investigated the adverse reactions owing to CAR-T therapy compared to that of clinically approved drugs. Thus, we aimed to elucidate the mechanisms, risk factors, diagnostic criteria, and treatment of toxicities concurrent with CRS, thereby providing a valuable reference for the safe, effective, and widespread application of CAR-T therapy.