Background/Objectives: Metastatic uveal melanoma (mUM) carries a poor prognosis and limited systemic treatment options. While immune checkpoint inhibitors have improved outcomes in cutaneous melanoma, their activity in mUM remains modest. Tebentafusp has recently emerged as the first therapy to improve overall survival in HLA-A*02:01–positive patients, but effective options for others remain scarce. This study compared the real-world effectiveness and safety of ipilimumab plus nivolumab versus anti-programmed cell death protein 1 (PD-1) monotherapy. Methods: We conducted a retrospective single-center analysis of patients with mUM treated at the National Institute of Oncology, Budapest. Patients received either dual checkpoint inhibition (ipilimumab plus nivolumab) or anti-PD-1 monotherapy (nivolumab or pembrolizumab). Evaluated outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and immune-related adverse events (irAEs). Survival was analyzed using Kaplan–Meier methods, log-rank tests, and Cox regression. Results: Fifty-five patients were included (33 ipilimumab–nivolumab, 22 anti-PD-1). ORR was 21% versus 5%, and DCR was 42% versus 32%, respectively. Median PFS was 5.8 vs. 3.7 months (p= 0.053; HR 0.61, 95% CI 0.34–1.09), and median OS was 12.3 vs. 10.6 months (p= 0.214; HR 0.66, 95% CI 0.36–1.22). Grade 3–4 irAEs occurred in 48% of patients receiving ipilimumab–nivolumab compared with 9% on monotherapy. No treatment-related deaths were observed. Conclusions: Anti-PD-1 monotherapy demonstrated limited clinical activity, providing little benefit beyond conventional chemotherapy. Dual checkpoint blockade with ipilimumab and nivolumab achieved higher response and disease control rates, albeit with increased toxicity, suggesting a potential benefit for selected patients. Tebentafusp has emerged as an effective option and a new standard of care for a molecularly defined subgroup of HLA-A*02:01–positive patients. However, for the majority of individuals with metastatic uveal melanoma, effective systemic therapies remain an unmet need.
背景/目的：转移性葡萄膜黑色素瘤（mUM）预后不良，全身治疗选择有限。尽管免疫检查点抑制剂改善了皮肤黑色素瘤的预后，但其在mUM中的疗效仍较为有限。Tebentafusp近期成为首个能改善HLA-A*02:01阳性患者总生存期的疗法，但针对其他患者的有效选择仍然稀缺。本研究比较了伊匹木单抗联合纳武利尤单抗与抗程序性细胞死亡蛋白1（PD-1）单药治疗在真实世界中的有效性和安全性。 方法：我们对布达佩斯国家肿瘤研究所收治的mUM患者进行了回顾性单中心分析。患者接受双检查点抑制治疗（伊匹木单抗联合纳武利尤单抗）或抗PD-1单药治疗（纳武利尤单抗或帕博利珠单抗）。评估指标包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）以及免疫相关不良事件（irAEs）。采用Kaplan-Meier法、对数秩检验和Cox回归进行生存分析。 结果：共纳入55例患者（33例接受伊匹木单抗-纳武利尤单抗治疗，22例接受抗PD-1单药治疗）。两组ORR分别为21% vs 5%，DCR分别为42% vs 32%。中位PFS为5.8个月 vs 3.7个月（p=0.053；HR 0.61，95% CI 0.34-1.09），中位OS为12.3个月 vs 10.6个月（p=0.214；HR 0.66，95% CI 0.36-1.22）。伊匹木单抗-纳武利尤单抗组3-4级irAEs发生率为48%，而单药治疗组为9%。未观察到治疗相关死亡事件。 结论：抗PD-1单药治疗的临床活性有限，相较于传统化疗未能提供明显获益。伊匹木单抗联合纳武利尤单抗的双检查点阻断治疗获得了更高的缓解率和疾病控制率，尽管毒性增加，提示其可能为特定患者带来获益。Tebentafusp已成为HLA-A*02:01阳性这一分子定义亚组患者的有效选择和新标准治疗。然而，对于大多数转移性葡萄膜黑色素瘤患者，有效的全身治疗方案仍是未满足的临床需求。
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