Ipilimumab for Patients With Advanced Mucosal Melanoma

• Published in: The oncologist (Dayton, Ohio) Ohio), 2013-06, Vol.18 (6), p.726-732
• Main Authors: Postow, Michael A., Luke, Jason J., Bluth, Mark J., Ramaiya, Nikhil, Panageas, Katherine S., Lawrence, Donald P., Ibrahim, Nageatte, Flaherty, Keith T., Sullivan, Ryan J., Ott, Patrick A., Callahan, Margaret K., Harding, James J., D'Angelo, Sandra P., Dickson, Mark A., Schwartz, Gary K., Chapman, Paul B., Gnjatic, Sacha, Wolchok, Jedd D., Hodi, F. Stephen, Carvajal, Richard D.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antigens, Neoplasm - biosynthesis; Cancer‐testis antigens; Clinical Trials as Topic; CTLA-4 Antigen - biosynthesis; CTLA‐4; Female; Humans; Immunotherapy; Ipilimumab; Male; Melanoma - drug therapy; Melanoma - pathology; Melanoma and Cutaneous Malignancies; Middle Aged; Mucosal melanoma; Mucous Membrane - drug effects; Mucous Membrane - pathology; Neoplasm Metastasis - drug therapy; Neoplasm Metastasis - pathology; Retrospective Studies; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Survival Analysis
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2012-0464

The outcome of patients with mucosal melanoma treated with ipilimumab is not defined. To assess the efficacy and safety of ipilimumab in this melanoma subset, we performed a multicenter, retrospective analysis of 33 patients with unresectable or metastatic mucosal melanoma treated with ipilimumab. The clinical characteristics, treatments, toxicities, radiographic assessment of disease burden by central radiology review at each site, and mutational profiles of the patients' tumors were recorded. Available peripheral blood samples were used to assess humoral immunity against a panel of cancer‐testis antigens and other antigens. By the immune‐related response criteria of the 30 patients who underwent radiographic assessment after ipilimumab at approximately week 12, there were 1 immune‐related complete response, 1 immune‐related partial response, 6 immune‐related stable disease, and 22 immune‐related progressive disease. By the modified World Health Organization criteria, there were 1 immune‐related complete response, 1 immune‐related partial response, 5 immune‐related stable disease, and 23 immune‐related progressive disease. Immune‐related adverse events (as graded by Common Terminology Criteria for Adverse Events version 4.0) consisted of six patients with rash (four grade 1, two grade 2), three patients with diarrhea (one grade 1, two grade 3), one patient with grade 1 thyroiditis, one patient with grade 3 hepatitis, and 1 patient with grade 2 hypophysitis. The median overall survival from the time of the first dose of ipilimumab was 6.4 months (range: 1.8–26.7 months). Several patients demonstrated serologic responses to cancer‐testis antigens and other antigens. Durable responses to ipilimumab were observed, but the overall response rate was low. Additional investigation is necessary to clarify the role of ipilimumab in patients with mucosal melanoma. 摘要 Ipilimumab 在粘膜黑色素瘤患者中的治疗结果还不清楚。为评估 ipilimumab 在这类黑色素瘤亚组中的疗效和安全性，我们针对33例 ipilimumab 治疗的不可切除或转移性粘膜黑色素瘤患者中开展了一项多中心回顾性研究。记录患者临床特征、治疗方案、毒性反应、每所研究中心统一放射学实验室对疾病负担进行的影像学评估，以及患者肿瘤的突变特征。收集外周血样本来评估针对癌症睾丸抗原与其他抗原的体液免疫。 Ipilimumab 治疗后约第12周时，利用免疫相关疗效标准分析30例接受影像学评估的患者，1例达到免疫相关完全缓解，1例为免疫相关的部分缓解，6例为免疫相关的疾病稳定，22例为免疫相关的疾病进展。根据改良的世界卫生组织标准，1例达到免疫相关的完全缓解，1例为免疫相关的部分缓解，5例为免疫相关的疾病稳定，23例为免疫相关的疾病进展。免疫相关的不良事件（基于通用不良事件术语标准4.0版进行分级），6例患者发生皮疹（4例为1级，2例为2级），3例发生腹泻（1例为1级，2例为3级），1例发生1级甲状腺炎，1例发生3级肝炎，1例发生2级下垂体炎。从 ipilimumab 第1剂次给药起计算的中位总生存期为6.4个月（范围，1.8∼26.7个月）。几例患者表现出对癌症睾丸抗原与其他抗原的血清学缓解。研究观察到对 ipilimumab 的持续缓解，但总缓解率偏低。有必要作进一步的研究，来明确 ipilimu