背景:本综述是欧洲临床微生物学和传染病学会(ESCMID)受损宿主感染研究小组(ESGICH)关于靶向和生物治疗安全性的共识文件的一部分。
目的:回顾,从传染病的角度来看,免疫检查点抑制剂的安全性,LFA-3靶向药物,细胞粘附抑制剂,鞘氨醇-1-磷酸受体调节剂和蛋白酶体抑制剂,并提出预防性建议。
方法:基于计算机的Medline搜索与每个药物或治疗家族相关的MeSH术语。
背景: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)靶向药物似乎不会固有地增加感染的风险,但会引起免疫相关的不良反应,需要额外的免疫抑制。尽管CD4+T细胞淋巴细胞减少与alefacept相关,没有观察到机会性感染。进行性多灶性白质脑病(PML)可能在使用那他珠单抗(抗α4整联蛋白单克隆抗体(mAb))和efalizumab(抗CD11amAb)治疗期间发生,但迄今为止尚未报告使用维多珠单抗(抗α4β7mAb)的病例。在PML高危患者中(抗JC多瘤病毒血清学阳性,血清抗体指数>1.5且治疗持续时间≥48个月),应仔细考虑继续使用那他珠单抗的获益-风险比.芬戈莫德可引起严重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。应考虑使用(val)阿昔洛韦和VZV疫苗接种进行预防。蛋白酶体抑制剂也会增加VZV感染的风险,和抗病毒预防(val)阿昔洛韦建议。在具有其他危险因素的多发性骨髓瘤患者(即高剂量皮质类固醇)中,可以考虑预防抗肺孢子虫。
结论:临床医生应意识到分别接受免疫检查点和细胞粘附抑制剂的患者发生免疫相关不良反应和PML的风险。
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.
BACKGROUND: 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).
CONCLUSIONS: Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.