Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Blood Cancer J. 2023 Aug 1;13(1):116. doi: 10.1038/s41408-023-00879-7.
Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more widely used in clinical practice. However, this new class of therapies is associated with a distinct adverse event (AE) profile that includes cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as AEs leading to increased infection risk such as cytopenias and hypogammaglobulinemia, and infections themselves. As preliminary data with this class of agents shows an increased risk of infections as compared with conventional MM treatment regimens, such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies (mAbs), guidance on infection monitoring, prophylaxis and treatment is required. This review provides consensus recommendations from a panel of 13 global experts, following a meeting in August 2022. The meeting objective was to review existing literature and identify relevant information on infections with all BsAbs in patients with MM, as well as to discuss clinical experience of experts in managing these infections. The recommendations outlined here can be used to guide management of infection risk factors, such as hypogammaglobulinemia and neutropenia. In addition, they can be used to guide the monitoring, prophylaxis, and treatment of bacterial, viral and fungal infections, including emerging infections of interest, such as coronavirus 2019 (COVID-19), and the use of vaccinations prior to and during BsAb treatment. The recommendations have been graded by the panel based on level of data available. Key recommendations include universal herpes simplex and varicella zoster virus prophylaxis, screening for hepatitis B virus reactivation risk in all patients, monthly intravenous immunoglobulin treatment for immunoparesis and in the absence of life-threatening infectious manifestations, use of colony-stimulating factors in patients with Grade 3 neutropenia, universal pneumocystis jirovecii pneumonia prophylaxis and no routine anti-fungal prophylaxis.
双特异性抗体 (BsAb) 作为一种新兴的免疫治疗药物，正在成为治疗多发性骨髓瘤 (MM) 的重要新型药物类别，并将在临床实践中得到更广泛的应用。然而，这种新型治疗方法与独特的不良事件 (AE) 谱相关，包括细胞因子释放综合征和免疫效应细胞相关神经毒性综合征，以及导致感染风险增加的 AE，如血细胞减少症和低丙种球蛋白血症，以及感染本身。由于此类药物的初步数据显示与免疫调节药物、蛋白酶体抑制剂和抗 CD38 单克隆抗体 (mAb) 等常规 MM 治疗方案相比，感染风险增加，因此需要有关感染监测、预防和治疗的指导。
本综述提供了 13 位全球专家小组的共识建议，该建议是在 2022 年 8 月的一次会议后制定的。会议的目的是审查现有文献，确定所有用于 MM 患者的 BsAb 相关感染的相关信息，并讨论专家在管理这些感染方面的临床经验。这里概述的建议可用于指导感染危险因素的管理，如低丙种球蛋白血症和中性粒细胞减少症。此外，它们还可用于指导细菌、病毒和真菌感染的监测、预防和治疗，包括新兴的感兴趣的感染，如 2019 年冠状病毒病 (COVID-19)，以及在 BsAb 治疗前和治疗期间使用疫苗。该小组根据现有数据的级别对建议进行了分级。主要建议包括普遍预防单纯疱疹病毒和带状疱疹病毒、对所有患者进行乙型肝炎病毒再激活风险筛查、每月静脉注射免疫球蛋白治疗免疫缺陷和无危及生命的感染表现、在中性粒细胞减少症 3 级患者中使用集落刺激因子、普遍预防卡氏肺孢子虫肺炎和不常规使用抗真菌预防。
