Kuo Ming-Chun, Su Po-Jung, Huang Chun-Chieh, Luo Hao-Lun, Chiu Tai-Jan, Li Shau-Hsuan, Wu Chia-Che, Liu Ting-Ting, Cheng Yuan-Tso, Kang Chih-Hsiung, Su Yu-Li
Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung, Taiwan.
Division of Hematology Oncology, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Front Oncol. 2020 Nov 27;10:584834. doi: 10.3389/fonc.2020.584834. eCollection 2020.
Immune checkpoint inhibitors (ICIs) are used widely for treating metastatic urothelial carcinoma (mUC). In practical settings, evidence is lacking on the efficacy of ICIs in some difficult-to-treat patients, such as those with end-stage renal disease (ESRD). Herein, we evaluate the safety and efficacy of ICIs for patients with mUC and ESRD.
For this retrospective study, patients with mUC who were given ICIs at Kaohsiung Chang Gang Memorial Hospital and Linkou Chang Gung Memorial Hospital between April 2016 and November 2019 were consecutively enrolled. All clinicopathologic data, treatment responses, and adverse events were recorded. The immune-related adverse events (AEs), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between ESRD and non-ESRD groups.
In total, 129 patients with mUC were enrolled, with 11 patients categorized as the ESRD group. Among these patients with ESRD receiving ICIs, 7 of 11 (63.6%) had high-grade (grade ≥3) AEs, chiefly hematologic toxicity. Some rarely encountered AEs were noted, including toxic epidermal necrolysis, tuberculosis reactivation, ascites, and cytokine release syndrome. Patients in the ESRD group had numerically higher ORR (54.5% vs. 28.8%, p = 0.09), PFS (7.1 vs. 3.5 months, p = 0.42), and OS (not reached vs. 15.4 months) than the non-ESRD group. A multivariate Cox regression model demonstrated that leukocytosis (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.23-5.63; p = 0.01) and neutrophil-to-lymphocyte ratio (HR 2.91; 95% CI: 1.30-6.53; p = 0.01) were independent prognostic factors.
Administration of ICIs in patients with mUC and ESRD demonstrated a modest antitumor activity, and should be used with caution for increasing risk of hematologic toxicity.
免疫检查点抑制剂（ICIs）被广泛用于治疗转移性尿路上皮癌（mUC）。在实际应用中，对于一些难以治疗的患者，如终末期肾病（ESRD）患者，ICIs的疗效缺乏证据。在此，我们评估ICIs对mUC合并ESRD患者的安全性和疗效。
在这项回顾性研究中，连续纳入2016年4月至2019年11月期间在高雄长庚纪念医院和林口长庚纪念医院接受ICIs治疗的mUC患者。记录所有临床病理数据、治疗反应和不良事件。比较ESRD组和非ESRD组的免疫相关不良事件（AEs）、客观缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
总共纳入129例mUC患者，其中11例被归类为ESRD组。在这些接受ICIs治疗的ESRD患者中，11例中有7例（63.6%）发生高级别（≥3级）AEs，主要是血液学毒性。还注意到一些罕见的AEs，包括中毒性表皮坏死松解症、结核再激活、腹水和细胞因子释放综合征。ESRD组患者的ORR（54.5%对28.8%，p = 0.09）、PFS（7.1对3.5个月，p = 0.42）和OS（未达到对15.4个月）在数值上高于非ESRD组。多变量Cox回归模型显示，白细胞增多（风险比[HR]：2.63；95%置信区间[CI]：1.23 - 5.63；p = 0.01）和中性粒细胞与淋巴细胞比值（HR 2.91；95% CI：1.30 - 6.53；p = 0.01）是独立的预后因素。
对mUC合并ESRD患者使用ICIs显示出适度的抗肿瘤活性，且因血液学毒性风险增加应谨慎使用。
