The Angeles Clinic & Research Institute, 2001 Santa Monica Blvd, Suite 560W, Santa Monica, CA 90404, USA.
Semin Oncol. 2010 Oct;37(5):440-9. doi: 10.1053/j.seminoncol.2010.09.004.
Malignant melanoma is rising faster in incidence than any other malignancy. Long-term remission or "cure" is rare and is almost exclusively limited to therapies that stimulate an immune antitumor response. Ipilimumab is a novel targeted human immunostimulatory monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4 (CTLA-4), an immune-inhibitory site expressed on activated T cells. Ipilimumab is well tolerated as an outpatient infusion therapy. Multiple studies have confirmed significant antimelanoma activity. A randomized trial has documented a survival benefit when ipilimumab was compared to a gp-100 vaccine only arm. The unique mechanism of action of ipilimumab makes assessment of response by conventional criteria difficult. Benefit from ipilimumab can occur after what would be considered progression with World Health Oganization (WHO) or Response Evaluation Criteria in Solid Tumors (RECIST) criteria. New immune response criteria have been proposed. Therapeutic responses peak between 12 and 24 weeks, with slow responses continuing up to and beyond 12 months. The major drug- related adverse side effects (10%-15% grade 3 or above) are immune-related and consist most commonly of rash, colitis, hypophysitis, thyroiditis, and hepatitis. Colonic perforation can occur and patients with diarrhea have to be monitored carefully with strict adherence to treatment algorithms. Algorithms for the treatment of other adverse side effects have been developed. The treatment of immune-related side effects with immunosuppressive agents, such as corticosteroids, does not appear to impair antitumor response. With proper monitoring and management of side effects, ipilimumab is an extremely safe drug to administer. The benefits of ipilimumab will most certainly extend to other malignancies in the near future.
恶性黑色素瘤的发病率上升速度比其他任何恶性肿瘤都快。长期缓解或“治愈”罕见，几乎仅限于刺激免疫抗肿瘤反应的治疗方法。Ipilimumab 是一种新型的靶向人免疫刺激单克隆抗体，可阻断细胞毒性 T 淋巴细胞抗原 4（CTLA-4），这是一种在激活的 T 细胞上表达的免疫抑制性位点。Ipilimumab 作为门诊输注治疗耐受性良好。多项研究证实了其对黑色素瘤的显著活性。一项随机试验表明，与 gp-100 疫苗组相比，Ipilimumab 具有生存获益。Ipilimumab 的独特作用机制使得根据常规标准评估反应变得困难。根据世界卫生组织（WHO）或实体瘤反应评估标准（RECIST）标准，在被认为进展后也可能受益于 Ipilimumab。已经提出了新的免疫反应标准。治疗反应在 12 至 24 周之间达到峰值，缓慢反应持续至 12 个月甚至更长时间。主要的药物相关不良副作用（10%-15%为 3 级或以上）是免疫相关的，最常见的是皮疹、结肠炎、垂体炎、甲状腺炎和肝炎。可能发生结肠穿孔，腹泻患者必须严格遵守治疗方案进行密切监测。已经开发出了用于治疗其他不良反应的方案。用免疫抑制剂（如皮质类固醇）治疗免疫相关副作用不会损害抗肿瘤反应。通过适当的监测和副作用管理，Ipilimumab 是一种非常安全的药物。在不久的将来，Ipilimumab 的益处肯定会扩展到其他恶性肿瘤。
