Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Cancer. 2013 Oct 15;119(20):3687-95. doi: 10.1002/cncr.28282. Epub 2013 Aug 2.
Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined.
To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated.
Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ≥ 1000 cells/μL at week 7 were associated significantly with survival.
In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed.
葡萄膜黑色素瘤的转移发生率很高；迄今为止，尚无明确改善预后的全身性治疗方法。抗细胞毒性 T 淋巴细胞相关蛋白 4（抗 CTLA-4）抗体伊匹单抗是转移性黑色素瘤的标准治疗方法；然而，CTLA-4 抑制在转移性葡萄膜黑色素瘤患者中的临床活性尚不清楚。
为了评估伊匹单抗在这种情况下的疗效，作者在美国和欧洲的 4 家中心进行了一项多中心回顾性分析。评估了临床特征、毒性以及通过中心、盲法放射学评估确定的放射性疾病负担。
共确定了 39 例葡萄膜黑色素瘤患者，其中 34 例患者接受了 3mg/kg 伊匹单抗治疗，5 例患者接受了 10mg/kg 伊匹单抗治疗。使用免疫相关反应标准和改良世界卫生组织标准评估了 12 周、23 周和总（中位随访时间为 50.4 周[12.6 个月]）时的反应率（RR）和联合反应加稳定疾病（SD）率。在第 12 周，RR 为 2.6%，反应加 SD 率为 46.0%；在第 23 周，RR 为 2.6%，反应加 SD 率为 28.2%。有 1 例完全缓解和 1 例迟发性部分缓解（在最初 SD 后 100 周），免疫相关 RR 为 5.1%。28 例患者（71.8%）出现免疫相关不良反应，包括 7 例（17.9%）3 级和 4 级事件。接受 10mg/kg 伊匹单抗治疗的患者比接受 3mg/kg 伊匹单抗治疗的患者更频繁出现免疫相关不良反应。从伊匹单抗首次给药开始的中位总生存期为 9.6 个月（95%置信区间，6.3-13.4 个月；范围，1.6-41.6 个月）。体能状态、乳酸脱氢酶水平和第 7 周时绝对淋巴细胞计数≥1000 个/μL 与生存显著相关。
在这项来自美国和欧洲 4 家医院的多中心回顾性分析中，观察到葡萄膜黑色素瘤患者对伊匹单抗的持久反应和可管理的毒性。
