Service of Infectious Disease, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
Department of Oncology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
Clin Microbiol Infect. 2018 Jun;24 Suppl 2(Suppl 2):S95-S107. doi: 10.1016/j.cmi.2018.01.030. Epub 2018 Feb 7.
The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies.
To review, from an infectious diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors, and to suggest preventive recommendations.
Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.
T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death (PD)-1/PD-1 ligand 1 (PD-L1)-targeted agents do not appear to intrinsically increase the risk of infection but can induce immune-related adverse effects requiring additional immunosuppression. Although CD4 T-cell lymphopenia is associated with alefacept, no opportunistic infections have been observed. Progressive multifocal leukoencephalopathy (PML) may occur during therapy with natalizumab (anti-α4-integrin monoclonal antibody (mAb)) and efalizumab (anti-CD11a mAb), but no cases have been reported to date with vedolizumab (anti-α4β7 mAb). In patients at high risk for PML (positive anti-JC polyomavirus serology with serum antibody index >1.5 and duration of therapy ≥48 months), the benefit-risk ratio of continuing natalizumab should be carefully considered. Fingolimod induces profound peripheral blood lymphopenia and increases the risk of varicella zoster virus (VZV) infection. Prophylaxis with (val)acyclovir and VZV vaccination should be considered. Proteasome inhibitors also increase the risk of VZV infection, and antiviral prophylaxis with (val)acyclovir is recommended. Anti-Pneumocystis prophylaxis may be considered in myeloma multiple patients with additional risk factors (i.e. high-dose corticosteroids).
Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.
本综述是欧洲临床微生物学和传染病学会（ESCMID）宿主易感性感染研究组（ESGICH）关于靶向和生物治疗安全性的共识文件的一部分。
从传染病的角度审查免疫检查点抑制剂、LFA-3 靶向药物、细胞黏附抑制剂、鞘氨醇-1-磷酸受体调节剂和蛋白酶体抑制剂的安全性概况，并提出预防建议。
基于计算机的 Medline 搜索，使用与每个药物或治疗家族相关的 MeSH 术语。
T 淋巴细胞相关抗原 4（CTLA-4）和程序性死亡（PD）-1/PD-1 配体 1（PD-L1）靶向药物似乎不会增加感染的固有风险，但会引起需要额外免疫抑制的免疫相关不良反应。尽管 CD4 T 细胞淋巴细胞减少与阿法赛普特有关，但尚未观察到机会性感染。在那他珠单抗（抗-α4-整联蛋白单克隆抗体（mAb））和依氟鸟氨酸（抗-CD11a mAb）治疗期间可能发生进行性多灶性白质脑病（PML），但迄今为止尚未报告使用维得利珠单抗（抗-α4β7 mAb）发生 PML 的病例。在 PML 风险较高的患者（抗-JC 多瘤病毒血清学阳性，血清抗体指数>1.5，治疗时间≥48 个月）中，应仔细考虑继续使用那他珠单抗的获益风险比。芬戈莫德诱导显著的外周血淋巴细胞减少，并增加水痘带状疱疹病毒（VZV）感染的风险。应考虑预防性使用（伐）昔洛韦和 VZV 疫苗接种。蛋白酶体抑制剂也会增加 VZV 感染的风险，建议预防性使用（伐）昔洛韦。对于多发性骨髓瘤患者，如有其他危险因素（即大剂量皮质类固醇），可考虑使用抗肺囊虫预防。
临床医生应意识到接受免疫检查点和细胞黏附抑制剂治疗的患者发生免疫相关不良反应和 PML 的风险。
