Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA.
Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):213-220. doi: 10.1182/asheducation-2018.1.213.
Genetic alterations of the / locus on chromosome 9p24.1 are a defining biological feature of classical Hodgkin lymphoma (HL). The resulting programmed death-ligand 1 (PD-L1) expression on Hodgkin Reed-Sternberg cells as well as the PD-L1 expressed in the HL microenvironment result in an ineffective host antitumor immune response and make HL a ripe target for programmed cell death-1 (PD-1) blockade. Anti-PD-1 antibody monotherapy has been effective and well tolerated in patients with relapsed or refractory (rel/ref) HL, with the majority of patients experiencing an objective response (approximately two-thirds of patients) and a median duration of response of 16.6 months in the study with the longest follow-up. Based on these data, nivolumab and pembrolizumab were approved by the US Food and Drug Administration (FDA) for the treatment of advanced rel/ref HL. Evidence has emerged that patients with HL benefit from continued PD-1 blockade beyond disease progression according to traditionally defined response criteria, and that the addition of, or switch to, chemotherapy after anti-PD-1 antibody failure can potentially re-induce clinical response. Subsequent studies have evaluated novel anti-PD-1-based combination regimens as well as the use of anti-PD-1 antibody therapy earlier in the course of a HL patient's therapy, including first salvage therapy for rel/ref disease (eg, nivolumab plus brentuximab vedotin) and even first-line treatment (eg, nivolumab added to doxorubicin, vinblastine, dacarbazine chemotherapy). The current role of PD-1 blockade in HL is as monotherapy in patients with advanced rel/ref disease, but the results of ongoing studies and the evolving treatment landscape in HL will determine the role of PD-1 blockade in the future.
9p24.1 染色体上 / 位点的基因改变是经典霍奇金淋巴瘤 (HL) 的明确生物学特征。由此导致的霍奇金氏 Reed-Sternberg 细胞程序性死亡配体 1 (PD-L1) 表达以及 HL 微环境中表达的 PD-L1 导致宿主抗肿瘤免疫反应无效，使 HL 成为程序性细胞死亡-1 (PD-1) 阻断的成熟靶点。抗 PD-1 抗体单药治疗在复发或难治性 (rel/ref) HL 患者中是有效的且耐受良好，大多数患者经历客观缓解（约三分之二的患者），在随访时间最长的研究中，中位缓解持续时间为 16.6 个月。基于这些数据，nivolumab 和 pembrolizumab 被美国食品和药物管理局 (FDA) 批准用于治疗晚期 rel/ref HL。有证据表明，根据传统定义的反应标准，HL 患者在疾病进展后继续接受 PD-1 阻断治疗获益，抗 PD-1 抗体治疗失败后加用或改用化疗可能会重新诱导临床缓解。随后的研究评估了新型抗 PD-1 联合方案以及在 HL 患者治疗过程中更早地使用抗 PD-1 抗体治疗，包括复发/难治性疾病的一线挽救治疗（如 nivolumab 联合 brentuximab vedotin）甚至一线治疗（如 nivolumab 加 doxorubicin、vinblastine、dacarbazine 化疗）。目前 PD-1 阻断在 HL 中的作用是作为晚期 rel/ref 疾病患者的单药治疗，但正在进行的研究结果和 HL 治疗领域的不断发展将决定 PD-1 阻断在未来的作用。
