Shindiapina Polina, Alinari Lapo
Department of Internal Medicine, Division of Hematology, Arthur G James Comprehensive Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH, USA.
Division of Hematology, Department of Internal Medicine, Ohio State University Wexner Medical Center, 410 West 12th Avenue, 481A Wiseman Hall, Columbus, Ohio, 43210, USA.
Ther Adv Hematol. 2018 Apr;9(4):89-105. doi: 10.1177/2040620718761777. Epub 2018 Mar 5.
Immune evasion is a critical mechanism of malignant cell survival, and relies in part on molecular signaling through the programmed cell death 1 (PD-1)/PD-1 ligand (PD-L1) axis that contributes to T cell exhaustion. Immune modulatory therapy with monoclonal antibodies against PD-1 designed to enhance antitumor immune response have shown promise in the treatment of advanced solid tumors and hematologic malignancies. Classical Hodgkin's lymphoma (cHL), a unique B cell malignancy characterized by an extensive but ineffective immune cell infiltrate surrounding a small number of tumor cells, has shown significant response to anti-PD-1 directed therapy. The anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have shown similarly remarkable activity in relapsed/refractory cHL and have been approved by the Food and Drug Administration for treatment of this disease. In this article we review the rationale of targeting the PD-1/PD-L1 axis in cHL and the pharmacology of pembrolizumab, and summarize the data on activity and safety profile of this agent in the treatment of relapsed/refractory cHL. We also discuss the potential benefits and pitfalls of using PD-1 blockade in the setting of allogeneic stem-cell transplantation, and summarize ongoing prospective trials of single-agent pembrolizumab and combination strategies as well as future directions.
免疫逃逸是恶性细胞存活的关键机制，部分依赖于通过程序性细胞死亡蛋白1（PD-1）/PD-1配体（PD-L1）轴的分子信号传导，这会导致T细胞耗竭。旨在增强抗肿瘤免疫反应的抗PD-1单克隆抗体免疫调节疗法在晚期实体瘤和血液系统恶性肿瘤的治疗中显示出前景。经典型霍奇金淋巴瘤（cHL）是一种独特的B细胞恶性肿瘤，其特征是在少数肿瘤细胞周围有广泛但无效的免疫细胞浸润，对抗PD-1定向治疗已显示出显著反应。抗PD-1单克隆抗体纳武单抗和派姆单抗在复发/难治性cHL中显示出同样显著的活性，并已获得美国食品药品监督管理局批准用于治疗该疾病。在本文中，我们回顾了在cHL中靶向PD-1/PD-L1轴的基本原理以及派姆单抗的药理学，并总结了该药物在复发/难治性cHL治疗中的活性和安全性数据。我们还讨论了在异基因干细胞移植中使用PD-1阻断的潜在益处和风险，并总结了正在进行的派姆单抗单药治疗和联合策略的前瞻性试验以及未来方向。
