Clinical Impact of Immunotherapy in Merkel Cell Carcinoma patients: A Systematic Review and Meta-Analysis

Background: Immunotherapy is emerging as an alternative for Merkel cell carcinoma (MCC), but its long-term effects on response, survival, and safety are not well established. High-quality evidence is needed to estimate its efficacy and its association with patients and tumor´s characteristics.
Objective: To summarize immunotherapy’s efficacy and safety in MCC patients.
Methods: A systematic review was performed for studies published in MEDLINE, Web of Science, Scopus, and EMBASE. Two reviewers reviewed the literature and data extraction in duplicate. We estimated the proportions for objective responses, progression free survival, overall survival, and treatment-related adverse events (TRAE). Associations between objective response rate (ORR) and immunobiological markers were analyzed.
Results: Six clinical trials of 201 patients treated with immunotherapy were included. The ORR was 51% (95%CI, 0.40-0.62; I2=37.1%) and grade ≥ 3 TRAE was observed in 18% (95%CI, 0.11-0.29; I2=49.5%) of patients. We observed no significant difference between response and immunobiological characteristics.
Conclusions: A significantly reduced tumor diameter with durable response rates and a safe profile are obtained with immunotherapy. Its association with immunobiological markers suggests that it may act on multiple pathways that achieve similar response rates on either tumor subtypes.

背景：免疫疗法正成为默克尔细胞癌（Merkel cell carcinoma, MCC）的替代治疗方案，但其在应答、生存及安全性方面的长期效应尚未明确，亟需高质量证据以评估其疗效，以及其与患者及肿瘤特征的相关性。
目的：总结免疫疗法用于默克尔细胞癌患者的疗效与安全性。
方法：本研究针对MEDLINE、Web of Science、Scopus及EMBASE数据库中已发表的研究开展系统综述，由两名研究者独立重复完成文献筛选与数据提取工作。我们对客观应答率（objective response rate, ORR）、无进展生存期、总生存期及治疗相关不良事件（treatment-related adverse events, TRAE）的占比进行了估算，并分析了客观应答率与免疫生物学标志物之间的关联。
结果：本研究共纳入6项临床试验，涉及201例接受免疫疗法治疗的患者。客观应答率为51%（95%CI：0.40~0.62；I²=37.1%），18%的患者出现≥3级治疗相关不良事件（95%CI：0.11~0.29；I²=49.5%）。未观察到应答情况与免疫生物学特征之间存在显著差异。
结论：免疫疗法可显著缩小肿瘤直径，且应答持久、安全性良好。其与免疫生物学标志物的关联提示，免疫疗法可能通过多条通路发挥作用，在不同肿瘤亚型中均可达到相近的应答率。