Division of Respiratory Medicine, Center for Respiratory Diseases, National Hospital Organization Kyoto Medical Center, 1-1, Fukakusa-Mukaihata, Fushimi-ku, Kyoto, 612-8555, Japan.
NIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Cancer Immunol Immunother. 2022 Nov;71(11):2757-2764. doi: 10.1007/s00262-022-03198-1. Epub 2022 Apr 16.
Recent advancements in cancer immunotherapy using immune checkpoint inhibitors (ICIs) have received considerable attention. Although advantageous, ICI therapies cause unique immune-related adverse events (irAEs) in some patients. Moreover, infectious diseases, such as tuberculosis, have been recognized as emerging concerns during immunotherapy. We aimed to evaluate the interferon-gamma release assay (IGRA) conversion rate and active tuberculosis incidence during immunotherapy to elucidate the incidence of tuberculosis reactivation after ICI therapy induction.We prospectively assessed IGRA results in lung cancer patients who received ICI monotherapy before ICI treatment and at 6 and 12 months after ICI treatment. We also assessed computed tomography findings to determine the presence of active tuberculosis when positive IGRA results were obtained. The ICIs used were nivolumab, pembrolizumab, atezolizumab, and durvalumab.In all, 178 patients were prospectively recruited between March 2017 and March 2020. Of these, 123 completed serial IGRAs, of whom 18, 101, and 4, respectively, had positive, negative, and indeterminate IGRAs at baseline. Three and four patients, respectively, showed IGRA reversion and conversion during immunotherapy. One patient with a sustained, stable positive IGRA and one with IGRA conversion developed active pulmonary tuberculosis during immunotherapy.We found that 3.3% and 1.6% of the patients developed IGRA conversion and active tuberculosis, respectively. Of the four patients who developed IGRA conversion, one developed active pulmonary tuberculosis during immunotherapy. Another patient with sustained, stable positive IGRA developed active tuberculosis. Physicians should be alert to tuberculosis development during ICI therapy, and IGRA testing is a useful tool to assess the risk of developing active tuberculosis.
最近，免疫检查点抑制剂（ICI）在癌症免疫治疗方面的进展受到了广泛关注。虽然这些疗法具有优势，但在某些患者中会引起独特的免疫相关不良反应（irAEs）。此外，免疫治疗期间还认识到传染病，如结核病，是一个新出现的问题。我们旨在评估免疫治疗期间干扰素-γ释放试验（IGRA）的转化率和活动性结核病的发生率，以阐明ICI 治疗诱导后结核病再激活的发生率。
我们前瞻性评估了接受 ICI 单药治疗的肺癌患者在 ICI 治疗前和 ICI 治疗后 6 个月和 12 个月的 IGRA 结果。我们还评估了计算机断层扫描结果，以确定在获得阳性 IGRA 结果时是否存在活动性结核病。使用的 ICI 药物为纳武利尤单抗、帕博利珠单抗、阿替利珠单抗和度伐利尤单抗。
总共前瞻性招募了 178 名患者，时间为 2017 年 3 月至 2020 年 3 月。其中 123 名患者完成了系列 IGRA，分别有 18、101 和 4 名患者基线时的 IGRA 结果为阳性、阴性和不确定。分别有 3 名和 4 名患者在免疫治疗期间出现 IGRA 逆转和转换。1 名持续稳定阳性 IGRA 的患者和 1 名 IGRA 转换的患者在免疫治疗期间发生了活动性肺结核。
我们发现，分别有 3.3%和 1.6%的患者发生了 IGRA 转换和活动性结核病。在发生 IGRA 转换的 4 名患者中，有 1 名在免疫治疗期间发生了活动性肺结核。另一名持续稳定阳性 IGRA 的患者发生了活动性结核病。医生应该警惕免疫治疗期间结核病的发生，IGRA 检测是评估发生活动性结核病风险的有用工具。
