癌症患者在接受 PD-1 阻断治疗时接种流感疫苗可诱导血清保护，但可能会增加免疫相关不良事件的风险。

Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.

机构信息

Department of Internal Medicine, Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.

Cancer Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.

出版信息

J Immunother Cancer. 2018 May 22;6(1):40. doi: 10.1186/s40425-018-0353-7.

DOI:10.1186/s40425-018-0353-7

PMID:29789020

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5964701/

Abstract

BACKGROUND

Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined.

METHODS

We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade.

RESULTS

We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%).

CONCLUSIONS

Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.

摘要

背景

免疫检查点抑制抗体已被引入癌症患者的常规临床实践中。检查点阻断在一些患者中导致了持久的缓解，但也可能引起免疫相关的不良反应（irAEs）。肺癌患者在感染流感病毒时，并发症的风险增加。因此，建议接种疫苗。然而，在检查点阻断期间接种流感疫苗的疗效和安全性及其对 irAEs 的影响尚不清楚。同样，疫苗接种对 PD-1 阻断期间患者 T 细胞介导的免疫反应的影响也尚未明确。

方法

我们使用三价灭活流感疫苗对 23 例肺癌患者和 11 名年龄匹配的健康对照者进行了疫苗接种，以研究检查点阻断期间疫苗接种引起的免疫和安全性。

结果

我们未观察到患者和健康对照者在针对所有三种病毒抗原的疫苗诱导抗体滴度方面存在显著差异。流感疫苗接种使超过 60%的患者/参与者产生了保护性滴度。在癌症患者中，irAEs 的疫苗接种后发生率为 52.2%，发生时间中位数为接种后 3.2 个月。23 例患者中有 6 例（26.1%）出现严重的 3/4 级 irAEs。irAEs 的这种发生率可能高于之前文献中报道的发生率，也高于我们机构非研究人群的发生率（所有等级为 25.5%，3/4 级为 9.8%）。