Background:Immune-related adverse events (irAEs) challenge the use of immune checkpoint inhibitors (ICIs). We performed a retrospective study to evaluate response to infliximab for immune-related adverse event management, and infliximab’s effect on progression-free survival (PFS) and overall survival (OS) with a focus on melanoma and genitourinary cancers.Methods:We retrospectively reviewed records of all cancer patients exposed to infliximab after immune checkpoint inhibitor (ICI) treatment from 2004 to 2021 at the MD Anderson Cancer Center. Survival was assessed utilizing the Kaplan–Meier method. Univariate and multivariate logistic regression was utilized to evaluate predictors of infliximab response, OS, and PFS.Results:We identified 185 cancer patients (93 melanoma and 37 genitourinary cancers) treated with ICI and who received infliximab to treat irAEs. Within 3 months of treatment initiation, 71% of the patients responded to infliximab, 27% had no response, and 2% had unknown response. Among different irAEs, colitis was associated with increased response to infliximab at 3 months, irrespective of the type of malignancy. We evaluated best tumor response before and after infliximab in the entire cohort and again in the melanoma and genitourinary (GU); the findings were similar in the melanoma cohort and the entire cohort, where best tumor response before and after infliximab was not significantly different. In the melanoma cohort, acute kidney injury (AKI) was associated with increased risk of death,p= 0.0109, and having response to infliximab was associated with decreased risk of death,p= 0.0383. Interestingly in GU cancer patients, myositis was associated with increased risk of death,p= 0.0041, and having a response to infliximab was marginally associated with decreased risk of death,p= 0.0992. As regards PFS, in a multivariate Cox regression model, having a history of cardiovascular disease remained significantly associated with shorter PFS in the melanoma cohort. For patients with GU cancers, response to infliximab was associated with longer PFS.Conclusions:Our study is among the largest retrospective analyses of infliximab use for irAE management. Patients with colitis were the best responders to infliximab. AKI before initiation of infliximab in the melanoma subcohort and myositis in GU subcohort are associated with higher risk of death. Our results indicate no association between infliximab and cancer progression with the exception of genitourinary cancers.
背景：免疫相关不良事件（irAEs）对免疫检查点抑制剂（ICIs）的应用构成挑战。本研究通过回顾性分析评估英夫利西单抗在免疫相关不良事件管理中的疗效，并重点探讨其对黑色素瘤和泌尿生殖系统癌症患者无进展生存期（PFS）及总生存期（OS）的影响。 方法：回顾性分析MD安德森癌症中心2004年至2021年间所有接受免疫检查点抑制剂治疗后使用英夫利西单抗的癌症患者病历。采用Kaplan-Meier法评估生存情况，通过单因素及多因素逻辑回归分析英夫利西单抗疗效、总生存期和无进展生存期的预测因素。 结果：共纳入185例接受免疫检查点抑制剂治疗并使用英夫利西单抗控制免疫相关不良事件的癌症患者（93例黑色素瘤，37例泌尿生殖系统肿瘤）。治疗启动3个月内，71%患者对英夫利西单抗产生应答，27%无应答，2%应答情况不明。在不同类型的免疫相关不良事件中，结肠炎与3个月时较高的英夫利西单抗应答率相关，且该关联不受恶性肿瘤类型影响。对全体队列及黑色素瘤/泌尿生殖系统亚组进行英夫利西单抗治疗前后最佳肿瘤应答评估发现：黑色素瘤亚组与全体队列结果相似，治疗前后最佳肿瘤应答无显著差异。在黑色素瘤亚组中，急性肾损伤与死亡风险升高相关（p=0.0109），而对英夫利西单抗产生应答与死亡风险降低相关（p=0.0383）。值得注意的是，在泌尿生殖系统肿瘤患者中，肌炎与死亡风险升高显著相关（p=0.0041），而对英夫利西单抗的应答与死亡风险降低呈边际相关性（p=0.0992）。关于无进展生存期，多因素Cox回归模型显示：在黑色素瘤亚组中，心血管疾病史与较短无进展生存期显著相关；而在泌尿生殖系统肿瘤患者中，对英夫利西单抗的应答与较长无进展生存期相关。 结论：本研究是目前规模最大的英夫利西单抗用于免疫相关不良事件管理的回顾性分析之一。结肠炎患者对英夫利西单抗的应答最佳。黑色素瘤亚组中英夫利西单抗治疗前出现急性肾损伤、泌尿生殖系统肿瘤亚组中出现肌炎均与较高死亡风险相关。研究结果表明除泌尿生殖系统肿瘤外，英夫利西单抗与癌症进展无显著关联。
Infliximab for Treatment of Immune Adverse Events and Its Impact on Tumor Response
肿瘤(癌症)患者之家