Sadjadian Parvis, Wille Kai, Griesshammer Martin
University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care Johannes Wesling Medical Center Minden, UKRUB, University of Bochum, Hans-Nolte-Straße 1, D-32429 Minden, Germany.
Cancers (Basel). 2020 Oct 26;12(11):3132. doi: 10.3390/cancers12113132.
Ruxolitinib (RUX), a JAK1/JAK2 inhibitor, is approved for second-line therapy in patients with polycythemia vera (PV) who are resistant or intolerant to hydroxyurea. Due to the immunomodulatory and immunosuppressive effect of RUX, there is an increased susceptibility to infections. However, an increased risk of infection is inherent to even untreated myeloproliferative neoplasms (MPN). To obtain more information on the clinical significance of RUX-associated infections in PV, we reviewed the available literature. There is no evidence-based approach to managing infection risks. Most data on RUX-associated infections are available for MF. In all studies, the infection rates in the RUX and control groups were fairly similar, with the exception of infections with the varicella zoster virus (VZV). However, individual cases of bilateral toxoplasmosis retinitis, disseminated molluscum contagiosum, or a mycobacterium tuberculosis infection or a hepatitis B reactivation are reported. A careful assessment of the risk of infection for PV patients is required at the initial presentation and before the start of RUX. Screening for hepatitis B is recommended in all patients. The risk of RUX-associated infections is lower with PV than with MF, but compared to a normal population there is an increased risk of VZV infection. However, primary VZV prophylaxis for PV patients is not recommended, while secondary prophylaxis can be considered individually. As early treatment is most effective for VZV, patients should be properly informed and trained to seek medical advice immediately if cutaneous signs of VZV develop. Vaccination against influenza, herpes zoster, and pneumococci should be considered in all PV patients at risk of infection, especially if RUX treatment is planned. Current recommendations do not support adjusting or discontinuing JAK inhibition in MPN patients to reduce the risk of COVID-19.
芦可替尼（RUX）是一种JAK1/JAK2抑制剂，已被批准用于对羟基脲耐药或不耐受的真性红细胞增多症（PV）患者的二线治疗。由于RUX的免疫调节和免疫抑制作用，患者感染易感性增加。然而，即使是未经治疗的骨髓增殖性肿瘤（MPN）本身就存在感染风险增加的情况。为了获取更多关于PV中与RUX相关感染的临床意义的信息，我们回顾了现有文献。目前尚无基于证据的感染风险管理方法。关于与RUX相关感染的大多数数据来自骨髓纤维化（MF）。在所有研究中，RUX组和对照组的感染率相当相似，但水痘带状疱疹病毒（VZV）感染除外。不过，有个别双侧弓形虫性视网膜炎、播散性传染性软疣、结核分枝杆菌感染或乙型肝炎再激活的病例报告。在PV患者初次就诊时以及开始使用RUX之前，需要仔细评估其感染风险。建议对所有患者进行乙型肝炎筛查。与MF相比，PV患者中与RUX相关的感染风险较低，但与正常人群相比，VZV感染风险增加。然而，不建议对PV患者进行原发性VZV预防，而继发性预防可个别考虑。由于早期治疗对VZV最有效，应适当告知患者并进行培训，使其在出现VZV皮肤症状时立即寻求医疗建议。对于所有有感染风险的PV患者，尤其是计划接受RUX治疗的患者，应考虑接种流感、带状疱疹和肺炎球菌疫苗。目前的建议不支持为降低COVID-19风险而调整或停用MPN患者的JAK抑制治疗。
