Machado Antonio Pizuorno, Ratliff Hunter, Abdelwahab Ahmed, Vohra Muhammad H, Kuang Andrew, Shatila Malek, Khan Muhammad Ali, Shafi Menhaz A, Thomas Anusha S, Philpott Jessica, Alhalabi Omar, Wang Yinghong
Department of Internal Medicine, The University of Texas Health Science Center, Houston, TX, USA.
Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Cancer. 2023 Sep 11;14(16):2956-2963. doi: 10.7150/jca.87335. eCollection 2023.
Immune checkpoint inhibitor (ICI) use can lead to immune-related adverse events (irAEs) that require treatment with immunosuppressive medications in moderate to severe cases. Oncology society guidelines recommend systemic steroids and immunosuppressants such as infliximab and vedolizumab for the treatment of refractory cases. Limited information is available about the safety profile and potential adverse effects of these immunosuppressants. We have investigated the safety profile of multiple immunosuppressants which are used in the treatment of ICI-related irAEs. We performed a systematic review of studies reporting irAEs, from ICI use, and their medical management with immunosuppressants in adult cancer patients. We searched MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov from inception through September 1, 2022, using the following keywords or their equivalents: ICI, immunosuppressant, and irAE. We extracted observational studies and clinical trials that matched our criteria. A random effects model was used to estimate the overall incidence of infections associated with the treatment of irAEs. Among the 11 studies included in this review (1036 total patients), melanoma (548 patients, 52.9%) was the most common primary cancer, followed by lung cancer (139 patients, 13.4%) and genitourinary cancers (131 patients, 12.6%). PD-1/PD-L1 monotherapy (460 patients, 44.4%) was used most, followed by a combination of PD-1/PD-L1 and CTLA-4 therapy (350 patients, 33.8%) and CTLA-4 monotherapy (226 patients, 22%). A total of 1024 (98.8%) patients had their irAEs treated with systemic steroids with majority having colitis and hepatobiliary irAEs; 335 patients (32.3%) were also treated with infliximab (mainly for colitis). Our review found 22.3% of patients treated for irAEs developed infectious adverse events (95% CI: 15.6%-29.1%, p<0.001). Among the 3 studies reporting the types of infections (41 total patients), bacterial (80.5%), followed by fungal (36.6%), infections were most common. Adverse events from irAE treatment occurred in about one-third of patients that received either steroids or a combination of steroids and other immunosuppressants. Clinicians should be aware of these immunosuppressant-related adverse effects, which can negatively impact cancer treatment and patient outcomes, when treating irAEs and consider shortening treatment duration or using alternative strategies when possible to mitigate these complications, future prospective studies should further investigate the safety of immunosuppressants in treating irAEs.
免疫检查点抑制剂（ICI）的使用可能会导致免疫相关不良事件（irAE），在中重度病例中需要使用免疫抑制药物进行治疗。肿瘤学会指南推荐使用全身性激素和免疫抑制剂，如英夫利昔单抗和维多珠单抗，来治疗难治性病例。关于这些免疫抑制剂的安全性和潜在不良反应的信息有限。我们调查了多种用于治疗ICI相关irAE的免疫抑制剂的安全性。我们对报告成人癌症患者使用ICI后出现的irAE及其用免疫抑制剂进行药物治疗的研究进行了系统评价。我们从数据库建立至2022年9月1日在MEDLINE、EMBASE、Cochrane图书馆和ClinicalTrials.gov中进行检索，使用以下关键词或其同义词：ICI、免疫抑制剂和irAE。我们提取了符合我们标准的观察性研究和临床试验。采用随机效应模型来估计与irAE治疗相关的感染总体发生率。在本综述纳入的11项研究（共1036例患者）中，黑色素瘤（548例患者，52.9%）是最常见的原发性癌症，其次是肺癌（139例患者，13.4%）和泌尿生殖系统癌症（131例患者，12.6%）。使用最多的是PD-1/PD-L1单药治疗（460例患者，44.4%），其次是PD-1/PD-L1与CTLA-4联合治疗（350例患者，33.8%）和CTLA-4单药治疗（226例患者，22%）。共有1024例（98.8%）患者的irAE接受了全身性激素治疗，大多数患者患有结肠炎和肝胆irAE；335例患者（32.3%）还接受了英夫利昔单抗治疗（主要用于治疗结肠炎）。我们的综述发现，接受irAE治疗的患者中有22.3%发生了感染性不良事件（95%CI：15.6%-29.1%，p<0.001）。在报告感染类型的3项研究（共41例患者）中，细菌感染（80.5%）最为常见，其次是真菌感染（36.6%）。接受激素或激素与其他免疫抑制剂联合治疗的患者中，约三分之一发生了irAE治疗相关的不良事件。临床医生在治疗irAE时应意识到这些与免疫抑制剂相关的不良反应，它们可能会对癌症治疗和患者预后产生负面影响，并在可能的情况下考虑缩短治疗时间或采用替代策略来减轻这些并发症，未来的前瞻性研究应进一步调查免疫抑制剂治疗irAE的安全性。
