Glutsch Valerie, Kneitz Hermann, Gesierich Anja, Goebeler Matthias, Haferkamp Sebastian, Becker Jürgen C, Ugurel Selma, Schilling Bastian
Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany.
Department of Dermatology, University Medical Center, Regensburg, Germany.
Cancer Immunol Immunother. 2021 Jul;70(7):2087-2093. doi: 10.1007/s00262-020-02832-0. Epub 2021 Jan 13.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy with poor prognosis. In Europe, approved systemic therapies are limited to the PD-L1 inhibitor avelumab. For avelumab-refractory patients, efficient and safe treatment options are lacking.
At three different sites in Germany, clinical and molecular data of patients with metastatic MCC being refractory to the PD-L1 inhibitor avelumab and who were later on treated with combined IPI/NIVO were retrospectively collected and evaluated.
Five patients treated at three different academic sites in Germany were enrolled. Three out of five patients investigated for this report responded to combined IPI/NIVO according to RECIST 1.1. Combined immunotherapy was well tolerated without any grade II or III immune-related adverse events. Two out of three responders to IPI/NIVO received platinum-based chemotherapy in between avelumab and combined immunotherapy.
In this small retrospective study, we observed a high response rate and durable responses to subsequent combined immunotherapy with IPI/NIVO in avelumab-refractory metastatic MCC patients. In conclusion, our data suggest a promising activity of second- or third-line PD-1- plus CTLA-4-blockade in patients with anti-PD-L1-refractory MCC.
默克尔细胞癌（MCC）是一种罕见的侵袭性神经内分泌皮肤恶性肿瘤，预后较差。在欧洲，获批的全身治疗仅限于程序性死亡受体配体1（PD-L1）抑制剂阿维鲁单抗。对于阿维鲁单抗难治性患者，缺乏有效且安全的治疗选择。
在德国的三个不同地点，回顾性收集并评估了对PD-L1抑制剂阿维鲁单抗难治且随后接受免疫检查点抑制剂伊匹单抗（IPI）/纳武单抗（NIVO）联合治疗的转移性MCC患者的临床和分子数据。
德国三个不同学术地点的五名患者入组。根据实体瘤疗效评价标准（RECIST）1.1，本报告所研究的五名患者中有三名对IPI/NIVO联合治疗有反应。联合免疫疗法耐受性良好，未出现任何二级或三级免疫相关不良事件。三名IPI/NIVO治疗有反应的患者中有两名在阿维鲁单抗和联合免疫疗法之间接受了铂类化疗。
在这项小型回顾性研究中，我们观察到阿维鲁单抗难治性转移性MCC患者对随后的IPI/NIVO联合免疫疗法有较高的反应率和持久反应。总之，我们的数据表明二线或三线程序性死亡受体1（PD-1）加细胞毒性T淋巴细胞相关蛋白4（CTLA-4）阻断疗法在抗PD-L1难治性MCC患者中具有良好的活性。
