Ciernik Amélie, Ciernik Laure, Bonczkowitz Peter, Morak Monika, Heinzerling Lucie, Bennaceur Yacine, Lawless Aleigha, Sullivan Ryan, Kött Julian, Gebhardt Christoffer, Carter Thomas J, Nathan Paul, Tschopp Sophie, Dummer Reinhard, Ramelyte Egle
Department of Dermatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Medical Faculty, University of Zurich, Zurich 8032, Switzerland.
Oncologist. 2025 Jul 4;30(7). doi: 10.1093/oncolo/oyaf173.
Uveal melanoma (UM) is the most common primary ocular malignancy with a high rate of metastases. While immune checkpoint inhibitors (ICIs), including ipilimumab and nivolumab (ipi + nivo), have shown efficacy in metastatic cutaneous melanoma, their success in metastatic UM (MUM) remains limited. This study evaluates toxicity and outcomes of ipi + nivo in the largest, multicenter MUM cohort.
We analyzed 131 MUM patients treated with ipi + nivo from 2016 to 2024 across 5 international centers. Rates of toxicity, response, and survival outcomes were assessed.
Among 131 patients, 37.4% of patients received 4 cycles of ipi + nivo. The most common reason for ipi + nivo discontinuation (31.3%) was toxicity. Of all treated patients, 80.2% experienced immune-related adverse events (irAEs). The overall response rate (ORR) was 16.4%, and the disease control rate (DCR) was 43.4%. Progression-free survival (PFS) was three months, and the median overall survival (OS) was 18 months. Patients receiving ipi + nivo as second-line therapy had lower ORR compared to patients who received ipi + nivo as first-line therapy (P = .04). Patients with exclusively extrahepatic metastases had a better ORR and OS compared to those with hepatic or mixed metastases (P = .02, P = .02, respectively). 20.6% of patients developed eosinophilia during treatment, which was associated with improved median OS (24 months vs 15 months, P = .02).
Ipi + nivo shows moderate efficacy and clinically relevant toxicities in patients with MUM. Eosinophilia is a potential prognostic biomarker, that merits further investigation.
葡萄膜黑色素瘤（UM）是最常见的原发性眼部恶性肿瘤，转移率很高。虽然包括伊匹单抗和纳武单抗（伊匹+纳武）在内的免疫检查点抑制剂在转移性皮肤黑色素瘤中已显示出疗效，但其在转移性UM（MUM）中的成功仍然有限。本研究评估了伊匹+纳武在最大的多中心MUM队列中的毒性和疗效。
我们分析了2016年至2024年期间在5个国际中心接受伊匹+纳武治疗的131例MUM患者。评估了毒性、反应和生存结果的发生率。
在131例患者中，37.4%的患者接受了4个周期的伊匹+纳武治疗。伊匹+纳武停药的最常见原因（31.3%）是毒性。在所有接受治疗的患者中，80.2%发生了免疫相关不良事件（irAE）。总缓解率（ORR）为16.4%，疾病控制率（DCR）为43.4%。无进展生存期（PFS）为3个月，中位总生存期（OS）为18个月。与接受伊匹+纳武一线治疗的患者相比，接受伊匹+纳武二线治疗的患者ORR较低（P = 0.04）。与有肝转移或混合转移的患者相比，仅发生肝外转移的患者ORR和OS更好（分别为P = 0.02，P = 0.02）。20.6%的患者在治疗期间出现嗜酸性粒细胞增多，这与中位OS改善相关（24个月对15个月，P = 0.02）。
伊匹+纳武在MUM患者中显示出中等疗效和临床相关毒性。嗜酸性粒细胞增多是一种潜在的预后生物标志物，值得进一步研究。
