Gong Emily, Zawacki Lauren, Fan Xinyi, Hippe Daniel S, Menon Ankita A, Remington Allison J, Lachance Kristina, Akaike Tomoko, Tachiki Lisa, Park Song Y, Nghiem Paul
Department of Dermatology, University of Washington, Seattle, Washington, USA.
Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
BMJ Oncol. 2025 Mar 6;4(1):e000654. doi: 10.1136/bmjonc-2024-000654. eCollection 2025.
Merkel cell carcinoma (MCC) is an aggressive skin cancer with poor outcomes in immunosuppressed patients. While immune checkpoint inhibitors (ICIs) achieve ~60% response rates in immunocompetent MCC patients, their efficacy in immunosuppressed patients remains unclear due to exclusion from trials. This study compares ICI outcomes, safety and the impact of immunosuppression subtypes between these groups.
This retrospective study analysed 183 advanced MCC patients on first-line ICIs from a Seattle-based data repository. Of these, 147 were immunocompetent, and 36 were immunosuppressed (chronic lymphocytic leukaemia (CLL) n=10, autoimmune disorders n=10, other haematologic malignancies n=9, solid organ transplants n=4 and HIV/AIDS n=3). Outcomes included objective response rate, disease progression, MCC-specific and overall survival probability, adjusted for age, sex and stage at ICI initiation.
Initial ICI response rates at 6 months were 50% in immunosuppressed and 61.5% in immunocompetent patients (HR=0.71, p=0.17). Immunosuppressed patients had higher risks of disease progression (2 years: 53.9% vs 42.1%, HR=1.65, p=0.05) and MCC-specific mortality (2 years: 38.7% vs 24.4%, HR=1.85, p=0.04). CLL patients (n=10) had a particularly low response rate (response rate: 20.0% vs 61.5%, HR=0.18, p=0.02) and high progression risk (2 years: 80.0% vs 42.1%, HR=4.09, p=0.01). Immunosuppressed patients faced higher rates of ICI toxicity (6-month risk: 51.6% vs 36.6%, HR=1.79, p=0.03).
ICIs provide meaningful benefits to immunosuppressed MCC patients, though their response rates are lower, and progression risk is higher compared with immunocompetent patients.
默克尔细胞癌（MCC）是一种侵袭性皮肤癌，在免疫抑制患者中预后较差。虽然免疫检查点抑制剂（ICI）在免疫功能正常的MCC患者中可达到约60%的缓解率，但由于被排除在试验之外，其在免疫抑制患者中的疗效仍不明确。本研究比较了这两组患者的ICI疗效、安全性以及免疫抑制亚型的影响。
这项回顾性研究分析了来自西雅图数据存储库的183例接受一线ICI治疗的晚期MCC患者。其中，147例免疫功能正常，36例免疫抑制（慢性淋巴细胞白血病（CLL）10例、自身免疫性疾病10例、其他血液系统恶性肿瘤9例、实体器官移植4例、HIV/AIDS 3例）。疗效指标包括客观缓解率、疾病进展、MCC特异性生存率和总生存率，并根据ICI开始时的年龄、性别和分期进行调整。
免疫抑制患者6个月时的初始ICI缓解率为50%，免疫功能正常患者为61.5%（HR=0.71，p=0.17）。免疫抑制患者疾病进展风险更高（2年：53.9%对42.1%，HR=1.65，p=0.05），MCC特异性死亡率更高（2年：38.7%对24.4%，HR=1.85，p=0.04）。CLL患者（n=10）缓解率特别低（缓解率：20.0%对61.5%，HR=0.18，p=0.02），疾病进展风险高（2年：80.0%对42.1%，HR=4.09，p=0.01）。免疫抑制患者ICI毒性发生率更高（6个月风险：51.6%对36.6%，HR=1.79，p=0.03）。
ICI对免疫抑制的MCC患者有显著益处，尽管与免疫功能正常患者相比，其缓解率较低，进展风险较高。
