Sibaud Vincent, Meyer Nicolas, Lamant Laurence, Vigarios Emmanuelle, Mazieres Julien, Delord Jean Pierre
aDepartment of Medical Oncology and Clinical Research bDepartment of Oncodermatology cDepartment of Pathology dDepartment of Oral Medicine, Institut Claudius Regaud, Institut Universitaire du Cancer, Toulouse Oncopole eDepartment of Oncopneumology, Hopital Larrey, Toulouse University, Toulouse, France.
Curr Opin Oncol. 2016 Jul;28(4):254-63. doi: 10.1097/CCO.0000000000000290.
The therapeutic use of anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab) is rapidly increasing. Given their mechanism of action that triggers T-cell activation, these immune checkpoint inhibitors induce specific adverse events that are mostly of immunologic origin. In this way, cutaneous toxicities represent the most frequent immune-related adverse events (irAEs). The purpose of this review is to summarize the most prevalent dermatologic complications induced by PD-1/PD-L1 immune checkpoint-blocking antibodies and to compare their dermatologic safety profile with anti-CTLA-4 ipilimumab.
More than 40% of melanoma patients treated with anti-PD-1 therapy are faced with dermatologic irAEs. However, these cutaneous complications usually remain self-limiting and readily manageable. Nonspecific macular papular rash and pruritus represent the most common manifestations. More characteristic lichenoid dermatitis or psoriasis may also develop. Vitiligo is also frequent in patients with melanoma but has not been reported in other types of solid cancers. Mucosal involvement may also occur, including xerostomia and lichenoid reactions. Although available data remain scarce, anti-PD-L1 antibodies present a similar dermatologic safety profile.
Dermatologic irAEs induced by PD-1 or PD-L1 blockade therapy rarely result in significant morbidity or permanent discontinuation of treatment. However, early recognition and appropriate management are crucial for restricting dose-limiting toxicities.
抗程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）抗体（纳武单抗、帕博利珠单抗）的治疗应用正在迅速增加。鉴于其触发T细胞活化的作用机制，这些免疫检查点抑制剂会引发主要源于免疫的特定不良事件。通过这种方式，皮肤毒性是最常见的免疫相关不良事件（irAE）。本综述的目的是总结由PD-1/PD-L1免疫检查点阻断抗体引起的最普遍的皮肤并发症，并将其皮肤安全性概况与抗细胞毒性T淋巴细胞相关抗原4（CTLA-4）的伊匹单抗进行比较。
接受抗PD-1治疗的黑色素瘤患者中，超过40%会出现皮肤irAE。然而，这些皮肤并发症通常具有自限性且易于处理。非特异性斑丘疹和瘙痒是最常见的表现。也可能出现更具特征性的苔藓样皮炎或银屑病。白癜风在黑色素瘤患者中也很常见，但在其他类型的实体癌中尚未见报道。也可能发生黏膜受累，包括口干和苔藓样反应。尽管现有数据仍然稀少，但抗PD-L1抗体呈现出相似的皮肤安全性概况。
由PD-1或PD-L1阻断疗法引起的皮肤irAE很少导致严重发病或治疗永久中断。然而，早期识别和适当处理对于限制剂量限制性毒性至关重要。
