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程序性细胞死亡-1 抑制剂治疗经典型霍奇金淋巴瘤。

Programmed Cell Death-One Inhibition Therapy in Classical Hodgkin Lymphoma.

机构信息

Department of Hematology and Oncology, Baylor College of Medicine, Houston, TX; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX.

Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.

出版信息

Clin Lymphoma Myeloma Leuk. 2021 Feb;21(2):e105-e111. doi: 10.1016/j.clml.2020.08.031. Epub 2020 Oct 2.

Abstract

The majority of patients with classical Hodgkin lymphoma (cHL) may be cured, but for patients with relapsed or refractory (R/R) cHL, the prognosis is unfavorable. Immune dysfunction is a significant contributor of relapse and a hallmark of cHL; in particular, the immune system is unable to eradicate lymphoma cells that overexpress immune checkpoint proteins. The blocking of this mechanism used by lymphoma cells to evade the immune system has resulted in clinical benefits. Use of checkpoint inhibitors (CPIs) in R/R cHL is associated with high response rates and an acceptable adverse effects profile. There is growing interest in combining chemotherapy with CPIs in frontline therapy of cHL treatment to improve relapse rates without significant additive toxicity. In this review, we discuss the current evidence supporting CPI use in R/R cHL and maintenance therapy. We present emerging CPI data in frontline adult cHL and assess its role in the elderly. In addition, we discuss critical immune-related toxicities and their management, and elaborate on the challenges of monitoring response and minimal residual disease as tools for maximizing efficacy by limiting toxicity.

摘要

大多数经典型霍奇金淋巴瘤(cHL)患者可以被治愈,但对于复发或难治性(R/R)cHL 患者,预后不佳。免疫功能障碍是复发的重要原因,也是 cHL 的标志;特别是,免疫系统无法消除过度表达免疫检查点蛋白的淋巴瘤细胞。阻断淋巴瘤细胞逃避免疫系统的这种机制导致了临床获益。在 R/R cHL 中使用检查点抑制剂(CPIs)与高反应率和可接受的不良事件谱相关。人们越来越感兴趣的是将化疗与 CPIs 联合用于 cHL 治疗的一线治疗,以提高缓解率,而不会显著增加毒性。在这篇综述中,我们讨论了支持 CPIs 在 R/R cHL 和维持治疗中的应用的现有证据。我们介绍了新出现的 CPIs 在一线成人 cHL 中的数据,并评估了其在老年人中的作用。此外,我们还讨论了免疫相关毒性的关键问题及其管理,并详细阐述了监测反应和微小残留疾病作为通过限制毒性最大限度提高疗效的工具的挑战。

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