ABSTRACT

Introduction

Classic Hodgkin lymphoma (cHL) is a cancer of the immune system. Combination chemotherapy and radiation therapy result in high cure rate, nevertheless, up to a quarter of patients with advanced stage cHL may relapse. One mechanism of relapse is through immune evasion; cHL can avoid immune destruction by manipulating T cell regulatory protein programmed cell death-1 (PD-1) and programmed cell death ligands 1 (PD-L1) and 2 (PD-L2) interaction. Immune checkpoint inhibitors (CPIs), such as pembrolizumab are effective in relapsed/refractory (R/R) cHL.

Areas covered

We reviewed prior and ongoing investigation of pembrolizumab use in R/R cHL, maintenance after autologous stem cell transplant (ASCT) and in frontline setting. Phase I study of pembrolizumab (KEYNOTE-013) demonstrated safety in R/R cHL with subsequent phase II study (KEYNOTE-087) confirmed efficacy signal. Intriguing early data support the use of maintenance pembrolizumab after ASCT in high-risk cHL patients. Second line and frontline studies incorporating CPIs have demonstrated promising efficacy with no significant additive toxicities.

Expert opinion

Immune CPIs that block PD-1/PD-L1 and PD-L2 interaction are an effective strategy in R/R cHL. Pembrolizumab demonstrated safety and efficacy in the treatment of R/R cHL. The optimal utilization of pembrolizumab in frontline therapy is under investigation.

中文翻译：

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派姆单抗治疗霍奇金淋巴瘤

摘要

介绍

经典霍奇金淋巴瘤（cHL）是免疫系统的癌症。然而，化学疗法和放射疗法的结合可达到较高的治愈率，但是，多达四分之一的晚期cHL患者可能会复发。复发的一种机制是通过免疫逃避。cHL可以通过操纵T细胞调节蛋白程序性细胞死亡1（PD-1）和程序性细胞死亡配体1（PD-L1）和2（PD-L2）相互作用来避免免疫破坏。免疫检查点抑制剂（CPI），例如pembrolizumab对复发/难治性（R / R）cHL有效。

覆盖区域

我们回顾了在R / R cHL中使用pembrolizumab的先前和正在进行的研究，自体干细胞移植（ASCT）后以及在一线治疗中的维持。pembrolizumab（KEYNOTE-013）的I期研究证明了R / R cHL的安全性，随后的II期研究（KEYNOTE-087）证实了疗效信号。有趣的早期数据支持在高危cHL患者中进行ASCT后使用维持性派姆单抗。结合CPI的二线和一线研究表明，疗效不错，并且没有明显的添加剂毒性。

专家意见

阻断PD-1 / PD-L1和PD-L2相互作用的免疫CPI是R / R cHL的有效策略。派姆单抗在R / R cHL的治疗中显示出安全性和有效性。目前正在研究对派姆单抗在前线治疗中的最佳利用。