Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical College, No. 300, Guangzhou Rode, Nanjing, 210029, China.
Department of Medical Oncology, Cancer Center of Jinling Hospital, No. 34, 34 Biao, Yanggongjing Street, Nanjing, 210002, China.
J Hematol Oncol. 2020 May 11;13(1):47. doi: 10.1186/s13045-020-00886-2.
Association of immune-related adverse events with tumor response has been reported. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event related to camrelizumab, an immune checkpoint inhibitor, but lack of comprehensive analyses. In this study, we conducted comprehensive analyses on RCCEP in advanced hepatocellular carcinoma (HCC) patients treated with camrelizumab monotherapy.
Data were derived from a Chinese nationwide, multicenter phase 2 trial of camrelizumab in pre-treated advanced HCC. The occurrence, clinicopathological characteristics, and prognostic value of RCCEP were analyzed.
With a median follow-up of 12.5 months, 145 of the 217 camrelizumab-treated patients (66.8%) experienced RCCEP (all grade 1 or 2). RCCEP occurred on the skin surface, mainly on the skin surface of head, face, and trunk. RCCEP could be divided into 5 types including "red-nevus-like," "pearl-like," "mulberry-like," "patch-like," and "tumor-like," according to the morphological features. RCCEP biopsy and pathology showed capillary endothelial hyperplasia and capillary hyperplasia in dermis. Significant association between RCCEP occurrence with higher objective response rate was observed (19.3% vs. 5.6%; one-sided p = 0.0044). Compared with those without RCCEP, patients with RCCEP had prolonged progression-free survival (median PFS; 3.2 months vs. 1.9 months; one-sided p < 0.0001) and overall survival (median OS; 17.0 months vs. 5.8 months; one-sided p < 0.0001). In multivariable analyses, the development of RCCEP was significantly associated with prolonged PFS and OS after adjusting for baseline covariates. In addition, the landmark analyses of PFS and OS were consistent with the unadjusted analysis.
RCCEP occurred on the skin surface and was an immune response of skin capillary endothelial cells. RCCEP occurrence positively associated with outcomes of camrelizumab in advanced HCC.
免疫相关不良反应与肿瘤应答之间存在关联。反应性皮肤毛细血管内皮增生症（RCCEP）是与免疫检查点抑制剂卡瑞利珠单抗相关的最常见不良反应，但缺乏全面分析。在这项研究中，我们对卡瑞利珠单抗单药治疗晚期肝细胞癌（HCC）患者的 RCCEP 进行了全面分析。
数据来自于卡瑞利珠单抗在中国开展的一项多中心、II 期、既往治疗的晚期 HCC 患者的全国性研究。分析了 RCCEP 的发生、临床病理特征和预后价值。
中位随访 12.5 个月时，217 例接受卡瑞利珠单抗治疗的患者中有 145 例（66.8%）发生 RCCEP（均为 1 级或 2 级）。RCCEP 发生于皮肤表面，主要发生于头、面、躯干的皮肤表面。根据形态特征，RCCEP 可分为“红痣样”、“珍珠样”、“桑葚样”、“斑块样”和“肿瘤样”5 种类型。RCCEP 活检和病理显示毛细血管内皮细胞增生和真皮内毛细血管增生。RCCEP 发生与客观缓解率显著相关（19.3% vs. 5.6%；单侧 p = 0.0044）。与无 RCCEP 患者相比，有 RCCEP 患者的无进展生存期（中位 PFS；3.2 个月 vs. 1.9 个月；单侧 p < 0.0001）和总生存期（中位 OS；17.0 个月 vs. 5.8 个月；单侧 p < 0.0001）更长。在多变量分析中，在校正基线协变量后，RCCEP 的发生与 PFS 和 OS 的延长显著相关。此外，PFS 和 OS 的里程碑分析与未调整分析一致。
RCCEP 发生于皮肤表面，是皮肤毛细血管内皮细胞的免疫反应。RCCEP 的发生与卡瑞利珠单抗治疗晚期 HCC 的疗效呈正相关。
