Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab
Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab
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DOI：
10.1001/jamadermatol.2015.2707
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发表时间：
2016-01-01
期刊：
影响因子：
10.9
通讯作者：
Robert, Caroline
中科院分区：
文献类型：
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作者：
Hua, Camille;Boussemart, Lise;Robert, Caroline
重要性 白癜风是一种自身免疫性皮肤病，会对黑色素细胞产生反应。白癜风与接受免疫治疗的黑色素瘤患者的肿瘤反应之间的关系已有报道，但仍存在争议。 目的 前瞻性评估接受派姆单抗（一种针对程序性死亡细胞受体的单克隆抗体）的患者白癜风的出现情况。 设计、设置和参与者 这项前瞻性观察性研究于 2012 年 1 月 1 日至 2013 年 9 月 24 日进行，在一项单项研究中进行。 三级护理医院，设有专门治疗黑色素瘤患者的科室。纳入了 67 名在 1 期研究中接受派姆单抗治疗的转移性黑色素瘤患者，并筛查了白癜风的出现情况。数据收集时间为2012年1月1日至2014年2月28日，分析时间为2014年2月至12月。 主要结果和措施接受派姆单抗治疗的患者中关于白癜风发生的客观肿瘤反应。还使用 Kaplan-Meier 乘积限法估计了白癜风发生率与总生存期之间的相关性，并与对数秩检验进行了比较。为了防止保证或交付时间偏倚，保留了治疗 12、16 和 20 周后的里程碑式分析方法。 结果 在研究纳入的 67 名患者中，17 名 (25%) 在派姆单抗治疗期间出现白癜风，50 名 (75%) 没有出现白癜风。对治疗的客观（完全或部分）反应与白癜风的较高发生率相关（17 例中的 12 例 [71%] vs 50 例中的 14 例 [28%]；P = .002）。从治疗开始到白癜风发病的时间为 52 至 453 天（中位数 126 天）。在最终随访时，17 例白癜风患者中，3 例（18%）有完全缓解，9 例（53%）有部分缓解，3 例（18%）病情稳定，2 例（12%）病情进展。所有接受派姆单抗治疗并出现白癜风的患者在分析时均存活，中位随访时间为 441 天。 结论和相关性 白癜风是一种临床可见的免疫相关不良事件，可能与派姆单抗治疗的临床获益相关。
IMPORTANCE Vitiligo is an autoimmune skin disorder that reacts against melanocytes. The association of vitiligo with tumor response in patients with melanoma who undergo immunotherapy has been reported but is still controversial.OBJECTIVE To prospectively evaluate the appearance of vitiligo in patients receiving pembrolizumab, a monoclonal antibody directed against the programmed death cell receptor.DESIGN, SETTING, AND PARTICIPANTS This prospective observational study was conducted from January 1, 2012, through September 24, 2013, in a single tertiary care hospital with a unit dedicated to patients with melanoma. Sixty-seven patients with metastatic melanoma who received pembrolizumab treatment in the context of a phase 1 study were included and screened for the emergence of vitiligo. Data were collected from January 1, 2012, to February 28, 2014, and analyzed from February through December 2014.MAIN OUTCOMES AND MEASURES Objective tumor response with regard to the occurrence of vitiligo in patients receiving pembrolizumab therapy. Correlation between vitiligo occurrence and overall survival was also estimated using the Kaplan-Meier product-limit method and compared with a log-rank test. To prevent guarantee-or lead-time bias, a landmark analysis approach after 12, 16, and 20 weeks of treatment was retained.RESULTS Of the 67 patients included in the study, 17 (25%) developed vitiligo during pembrolizumab treatment and 50 (75%) did not. An objective (complete or partial) response to treatment was associated with a higher occurrence of vitiligo (12 of 17 [71%] vs 14 of 50 [28%]; P = .002). The time to onset of vitiligo ranged from 52 to 453 (median, 126) days from the start of treatment. Of the 17 patients with vitiligo, 3 (18%) had a complete response, 9 (53%) had a partial response, 3 (18%) had stable disease, and 2 (12%) had progressive disease at the final follow-up. All the patients treated with pembrolizumab who developed vitiligo were alive at the time of analysis, with a median follow-up of 441 days.CONCLUSIONS AND RELEVANCE Vitiligo, a clinically visible immune-related adverse event could be associated with clinical benefit in the context of pembrolizumab treatment.