Vitiligo expansion and extent correlate with durable response in anti-programmed death 1 antibody treatment for advanced melanoma: A multi-institutional retrospective study
Vitiligo expansion and extent correlate with durable response in anti-programmed death 1 antibody treatment for advanced melanoma: A multi-institutional retrospective study
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DOI：
10.1111/1346-8138.15345
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发表时间：
2020-06-01
影响因子：
3.1
通讯作者：
Yamamoto, Akifumi
中科院分区：
文献类型：
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作者：
Matsuya, Taisuke;Nakamura, Yasuhiro;Yamamoto, Akifumi
白癜风是一种自身免疫性疾病，由黑素细胞破坏引起。一些报告表明，白癜风和免疫治疗期间晚期黑色素瘤的治疗反应之间的关联。然而，尚未研究过抗程序性死亡1（PD-1）抗体治疗时白癜风的增加是否与更持久的反应有关。本研究的目的是评估白癜风动态与抗PD-1抗体临床疗效之间的相关性。该研究包括用nivolumab或pembrolizumab治疗的晚期黑色素瘤患者，此后发展为白癜风。评估了白癜风扩展（定义为在至少相隔4周的两个不同时间点病灶大小增加）以及白癜风程度（受影响的体表面积[BSA]）与基于缓解率、无进展生存期和总生存期的临床疗效之间的相关性。我们回顾了29例患者。从抗PD-1抗体开始到白癜风发作的中位时间在显示应答的患者中为4.3个月，在显示无应答的患者中为5.5个月（P = 0.31）。12例患者显示白癜风扩展，其中9例患者的白癜风增加到2级（覆盖>= 10%BSA）。白癜风扩展和2级白癜风显示治疗反应没有改善（P = 0.59和0.25），但与无进展生存期延长相关（P = 0.019和0.04）。2级白癜风也显示出延长总生存期的趋势（P = 0.07）。抗PD-1抗体治疗期间，白癜风的扩展趋势和更大的范围可能是黑色素瘤患者生存期延长的预测因素。
Vitiligo is an autoimmune disorder resulting from the destruction of melanocytes. Several reports indicate the association between vitiligo and treatment response in advanced melanoma during immunotherapy. It has not been investigated, however, if an increase of vitiligo while on treatment with anti-programmed death 1 (PD-1) antibodies is associated with more durable responses. The aim of this study is to evaluate the correlation between the vitiligo dynamics and clinical efficacy of anti-PD-1 antibodies. This study included advanced melanoma patients who were treated with nivolumab or pembrolizumab and developed vitiligo thereafter. Correlation between vitiligo expansion (defined as an increase of lesion size at two separate time points at least 4 weeks apart) as well as vitiligo extent (body surface area [BSA] affected) and clinical efficacy based on response rate, progression-free survival and overall survival was assessed. We retrospectively reviewed 29 patients. The median time from the initiation of anti-PD-1 antibody to vitiligo onset was 4.3 months in patients who showed a response and 5.5 months in patients who showed no response (P = 0.31). Twelve patients showed vitiligo expansion, and in nine of these patients, vitiligo increased to grade 2 (covering >= 10% BSA). Vitiligo expansion and grade 2 vitiligo showed no improvement in treatment response (P = 0.59 and 0.25) but were associated with prolonged progression-free survival (P = 0.019 and 0.04). Grade 2 vitiligo also showed a trend for prolonged overall survival (P = 0.07). Trend of expansion and larger vitiligo extent may be predictive factors of prolonged survival during anti-PD-1 antibody in melanoma patients.