Zimmer Lisa, Goldinger Simone M, Hofmann Lars, Loquai Carmen, Ugurel Selma, Thomas Ioannis, Schmidgen Maria I, Gutzmer Ralf, Utikal Jochen S, Göppner Daniela, Hassel Jessica C, Meier Friedegund, Tietze Julia K, Forschner Andrea, Weishaupt Carsten, Leverkus Martin, Wahl Renate, Dietrich Ursula, Garbe Claus, Kirchberger Michael C, Eigentler Thomas, Berking Carola, Gesierich Anja, Krackhardt Angela M, Schadendorf Dirk, Schuler Gerold, Dummer Reinhard, Heinzerling Lucie M
Department of Dermatology, University Hospital, University Duisburg-Essen, Germany.
Department of Dermatology, University Hospital Zurich, Switzerland.
Eur J Cancer. 2016 Jun;60:210-25. doi: 10.1016/j.ejca.2016.02.024. Epub 2016 Apr 13.
Anti-programmed cell death 1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma and other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects can involve skin, gastrointestinal tract, liver, the endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.
In total, 496 patients with metastatic melanoma from 15 skin cancer centres were treated with pembrolizumab or nivolumab. Two hundred forty two side-effects in 138 patients have been analysed. In 77 of the 138 patients side-effects affected the nervous system, respiratory tract, musculoskeletal system, heart, blood and eyes. Not yet reported side-effects such as meningo-(radiculitis), polyradiculitis, cardiac arrhythmia, asystolia, and paresis have been observed. Rare and difficult to manage side-effects such as myasthenia gravis are described in detail.
Anti-PD-1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.
抗程序性细胞死亡蛋白1（PD-1）抗体是转移性黑色素瘤和其他癌症实体的一种有效治疗选择。它们通过阻断PD-1受体发挥作用，PD-1受体是限制针对肿瘤的免疫反应的T细胞效应机制的抑制剂。正如伊匹单抗的报道一样，抗PD-1抗体派姆单抗和纳武单抗可诱发免疫相关不良事件（irAE）。这些副作用可能累及皮肤、胃肠道、肝脏、内分泌系统和其他器官系统。由于已报道有危及生命和致命的irAE，因此进行充分的诊断和管理至关重要。
来自15个皮肤癌中心的总共496例转移性黑色素瘤患者接受了派姆单抗或纳武单抗治疗。对138例患者的242种副作用进行了分析。在这138例患者中，有77例的副作用影响了神经系统、呼吸道、肌肉骨骼系统、心脏、血液和眼睛。观察到了尚未报道的副作用，如脑膜（神经根炎）、多发性神经根炎、心律失常、心搏停止和轻瘫。详细描述了如重症肌无力等罕见且难以处理的副作用。
抗PD-1抗体可诱发大量irAE。了解这些副作用将有助于及时诊断并改善管理，从而降低发病率。
