Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia.
Blood Rev. 2021 Sep;49:100810. doi: 10.1016/j.blre.2021.100810. Epub 2021 Feb 27.
Relapsed haematological malignancies have a poor disease prognosis with current therapies. Bispecific antibodies (BsAbs) are becoming increasingly recognised for their efficacy in the treatment of these malignancies and are approved for the treatment of B-cell acute lymphoblastic leukaemia (B-ALL). BsAbs are manufactured to consist two variable chain fragments combined by a peptide linker amongst other structures to increase the half-life of the molecules. BsAbs function by bringing targeted tumour cells in close proximity of T-cells to allow killing via perforin and granzyme release. The increasing numbers of trials of BsAbs has highlighted their toxicity profile, including cytokine release syndrome (CRS), cytopaenia and hypogammaglobulinemia - which all increase risks for infection. The patterns and risks for infections with these novel agents remain unclear. This review article provides an overview of the risks of infection with various BsAbs platforms. A review of clinical trials reveals rates of infections amongst patients on BsAbs between 15 and 45% with a high proportion grade 3 severity or higher. A predominance of bacterial respiratory and line-related infections were identified amongst all haematological malignancies. In particular, high rates of febrile neutropaenia were identified in use of BsAbs in myeloid malignancy. Infection patterns identified in this review are utilised to inform infection prevention practice, including focused infection screening, line management, prophylaxis and vaccination strategies. Prophylaxis strategies against Pneumocystis pneumonia, herpes simplex and herpes zoster, candida and mould infections are considered, along with vaccination strategies against respiratory viral and bacterial infections. The long-term impacts of BsAbs on the immune system continue to be established.
复发的血液系统恶性肿瘤目前的治疗方法预后较差。双特异性抗体（BsAbs）因其在治疗这些恶性肿瘤中的疗效而越来越受到认可，并已被批准用于治疗 B 细胞急性淋巴细胞白血病（B-ALL）。BsAbs 的制造是由两个可变链片段组成，通过肽接头等结构结合在一起，以增加分子的半衰期。BsAbs 通过将靶向肿瘤细胞与 T 细胞紧密结合，允许通过穿孔素和颗粒酶的释放来杀死肿瘤细胞。越来越多的 BsAbs 试验强调了其毒性特征，包括细胞因子释放综合征（CRS）、细胞减少症和低丙种球蛋白血症——所有这些都会增加感染的风险。这些新型药物感染的模式和风险仍不清楚。本文综述了各种 BsAbs 平台感染的风险。对临床试验的回顾显示，BsAbs 治疗患者的感染率在 15%至 45%之间，其中相当大比例为 3 级或更高级别的严重程度。所有血液系统恶性肿瘤中均发现以细菌呼吸道和导管相关感染为主。特别是在使用 BsAbs 治疗髓系恶性肿瘤时，中性粒细胞减少性发热的发生率很高。本综述中确定的感染模式用于为感染预防实践提供信息，包括针对性的感染筛查、导管管理、预防和疫苗接种策略。考虑了预防卡氏肺孢子菌肺炎、单纯疱疹和带状疱疹、念珠菌和霉菌感染的策略，以及预防呼吸道病毒和细菌感染的疫苗接种策略。BsAbs 对免疫系统的长期影响仍在不断确立。
