转移性 Merkel 细胞癌患者的免疫检查点抑制剂反应的临床、FDG-PET 和分子标志物。
Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma.
机构信息
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Department of Clinical Pathology and Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.
出版信息
J Immunother Cancer. 2020 Oct;8(2). doi: 10.1136/jitc-2020-000700.
BACKGROUND
Metastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials.
METHODS
Medical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed.
RESULTS
23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1-2 immune-related adverse events.
CONCLUSION
ICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.
背景
转移性 Merkel 细胞癌（mMCC）是一种侵袭性的皮肤神经内分泌恶性肿瘤，预后较差。免疫检查点抑制剂（ICIs）在临床试验中显示出显著的疗效和良好的安全性。
方法
分析了 2015 年 8 月至 2018 年 12 月在澳大利亚彼得麦卡伦癌症中心接受 ICI 治疗的 mMCC 患者的病历。通过连续影像学检查评估反应，大多数采用 FDG-PET/CT 扫描。对肿瘤样本进行 RNA 测序和 PD-L1、CD3 和 Merkel 细胞多瘤病毒（MCPyV）的免疫组化分析。
结果
23 例 mMCC 患者接受了 ICI 治疗。中位治疗周期为 8 个周期（范围 1 至 47 个），6 例患者仍在治疗中。14 例患者（61%）观察到客观缓解（OR）：10 例（44%）完全缓解（CR）和 4 例（17%）部分缓解（PR）。中位缓解时间为 8 周（范围 6 至 12 周），12 个月无进展生存率为 39%。在年龄小于 75 岁的患者（OR 80% vs 46%）、无化疗史的患者（OR 64% vs 50%）、发生免疫相关不良事件的患者（OR 100% vs 43%）和 MCPyV 阴性肿瘤的患者（OR 69% vs 43%）中，OR 增加。在基线 FDG-PET/CT 扫描中，CR 患者的平均代谢肿瘤体积较低（CR：35.7mL，无 CR：187.8mL，p=0.05）。PD-L1 阳性与 MCPyV 状态（p=0.764）或 OR（p=0.245）之间无相关性。10 例患者在 ICI 期间接受了放疗（RT）：4 例患者同时开始 RT（OR 75%，CR 50%），3 例患者孤立的 ICI 耐药病变成功接受 RT 治疗，3 例多部位进展的患者尽管接受了 RT 仍继续进展。总体而言，6 例患者（26%）发生 1-2 级免疫相关不良事件。
结论
ICI 在 mMCC 中的疗效和安全性与试验数据一致。确定了反应的临床和影像学预测因素。
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