Delyon Julie, Maio Michele, Lebbé Celeste
AP-HP, Hôpital Saint-Louis, Département de Dermatologie, Paris, France; INSERM U976, Paris 7 University, Paris, France.
Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy.
Semin Oncol. 2015 Jun;42(3):387-401. doi: 10.1053/j.seminoncol.2015.02.005. Epub 2015 Feb 17.
The anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) antibody ipilimumab is the first treatment that significantly improved the survival rates of metastatic melanoma patients, marking a new era in the treatment of melanoma. During its development, a hallmark of ipilimumab therapy was the extended duration of response, achieved in 20% of patients. The follow-up of patients included in phase II and phase III trials and in expanded access programs revealed that the survival rates remained stable after 3 years. These results demonstrated that ipilimumab induces an effective anti-tumor immune response persisting after the completion of treatment, and suggested a potential remission in a subset of patients. In this article we review the development of ipilimumab and highlight the long-term results. This approach emphasizes the need to optimize the use of ipilimumab in the future, by identifying the patients most likely to achieve long term survival after ipilimumab therapy, and by developing combined therapeutic approaches involving cytotoxic agents, targeted therapies or other immunotherapies to achieve durable control in a larger proportion of patients.
抗细胞毒性T淋巴细胞抗原4（抗CTLA-4）抗体伊匹木单抗是首个显著提高转移性黑色素瘤患者生存率的治疗药物，标志着黑色素瘤治疗进入了一个新时代。在其研发过程中，伊匹木单抗治疗的一个显著特点是反应持续时间延长，20%的患者实现了这一点。对纳入II期和III期试验以及扩大准入项目的患者进行随访发现，3年后生存率保持稳定。这些结果表明，伊匹木单抗可诱导有效的抗肿瘤免疫反应，在治疗结束后仍持续存在，并提示一部分患者可能实现缓解。在本文中，我们回顾了伊匹木单抗的研发过程并强调了长期结果。这种方法强调未来需要优化伊匹木单抗的使用，通过识别最有可能在伊匹木单抗治疗后实现长期生存的患者，并通过开发涉及细胞毒性药物、靶向治疗或其他免疫治疗的联合治疗方法，以在更大比例的患者中实现持久控制。
