Department of Dermatology, Division of General Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
Med Oncol. 2011 Dec;28(4):1140-4. doi: 10.1007/s12032-010-9606-0. Epub 2010 Jul 1.
Malignant melanoma is an aggressive skin cancer with no effective therapies currently approved for advanced disease. In the case presented, a 55-year-old female patient diagnosed with widespread disease from amelanotic desmoplastic melanoma was treated with 10 mg/kg ipilimumab as part of a phase II clinical trial (CA184-008). Prior to ipilimumab, three chemotherapeutic regimens had failed. Ipilimumab acts as a T-cell potentiator via blockade of cytotoxic T-lymphocyte antigen-4, a negative regulator of T-cell activation. Response to ipilimumab treatment was rapid, with a substantial drop in tumor volume within 12 weeks of treatment initiation. Based on the appearance of a new subcutaneous lesion, reinduction with ipilimumab was performed at Week 30. Following reinduction, the appearance of another small new lesion made the patient ineligible, as per protocol, for further dosing despite stabilization of her remaining lesions. Ipilimumab-associated immune-related adverse events were manageable with the use of treatment guidelines. It is of remarkable immunotherapeutic importance that no new lesions emerged and gradual tumor regression is still ongoing more than 2 years following the last dose of ipilimumab, despite daily administration of systemic corticosteroids to manage drug-induced AEs. The ongoing clinical response is maintained without any further antineoplastic treatment.
恶性黑色素瘤是一种侵袭性皮肤癌,目前尚无针对晚期疾病的有效治疗方法。在本例中,一名 55 岁女性患者被诊断为无黑色素性促结缔组织增生性黑色素瘤广泛转移,接受了 10mg/kg 的 ipilimumab 治疗,这是一项 II 期临床试验(CA184-008)的一部分。在使用 ipilimumab 之前,三种化疗方案均失败。Ipilimumab 通过阻断细胞毒性 T 淋巴细胞抗原-4(T 细胞激活的负调节剂)发挥 T 细胞增强作用。Ipilimumab 治疗的反应迅速,在治疗开始后 12 周内肿瘤体积显著下降。基于新出现的皮下病变,在第 30 周重新开始使用 ipilimumab 诱导治疗。重新诱导后,尽管其余病变稳定,但根据方案,由于出现另一个新的小病变,患者不适合进一步给药。根据治疗指南,使用 ipilimumab 相关的免疫相关不良反应是可控的。值得注意的是,尽管每天给予全身皮质类固醇以管理药物引起的不良反应,在最后一次使用 ipilimumab 后超过 2 年,仍未出现新病变,且肿瘤逐渐消退。在没有任何其他抗肿瘤治疗的情况下,持续的临床反应得以维持。