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识别和治疗多发性骨髓瘤和淋巴瘤中检查点抑制剂治疗的候选者。

Identifying and treating candidates for checkpoint inhibitor therapies in multiple myeloma and lymphoma.

机构信息

Department of Haematooncology, University Hospital Ostrava, Ostrava, Czech Republic.

Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.

出版信息

Expert Rev Hematol. 2020 Apr;13(4):375-392. doi: 10.1080/17474086.2020.1733405. Epub 2020 Mar 2.

Abstract

: One of the hallmarks of cancerogenesis is the ability of tumor cells to evade the immune system. They can achieve it by abusing inhibitory immune checkpoint pathways, which, under normal circumstances, maintain peripheral tolerance during infection. Immune checkpoint inhibitors, especially anti-PD-1/PD-L1 monoclonal antibodies, currently represent a widely discussed treatment option not only in solid oncology, but in hematology-oncology as well.: The manuscript is focused on clinical research concerning PD-1/PD-L1 blockade in lymphoma and multiple myeloma in order to identify the patients who would profit the most from this treatment modality. The authors reviewed articles on the topic on PubMed and relevant clinical trials on clinicaltrials.gov before October 2019.: So far, nivolumab and pembrolizumab have been approved for treating patients with relapsed/refractory classical Hodgkin lymphoma and primary mediastinal B cell lymphoma. Nevertheless, monotherapy alone is not curative and a combinational approach is needed. Modern treatment strategies and combinations are comprehensively summarized in this manuscript. There is no approved immune checkpoint inhibitor for the multiple myeloma indication. Although the combination of PD-1/PD-L1 inhibitors with immunomodulatory agents initially seemed promising, unexpected immune related toxicities have stopped any further development. Novel strategies and more potent combinations in myeloma and lymphoma are further discussed in the manuscript.

摘要

癌症发生的一个特征是肿瘤细胞逃避免疫系统的能力。它们可以通过滥用抑制性免疫检查点途径来实现这一点,在正常情况下,这些途径在感染期间维持外周耐受。免疫检查点抑制剂,特别是抗 PD-1/PD-L1 单克隆抗体,目前不仅在实体肿瘤学中,而且在血液肿瘤学中,都是一种广泛讨论的治疗选择。

本文专注于关于淋巴瘤和多发性骨髓瘤中 PD-1/PD-L1 阻断的临床研究,以确定哪些患者最受益于这种治疗方式。作者在 2019 年 10 月之前在 PubMed 上查阅了关于该主题的文章和在 clinicaltrials.gov 上的相关临床试验。

到目前为止,nivolumab 和 pembrolizumab 已被批准用于治疗复发/难治性经典霍奇金淋巴瘤和原发性纵隔 B 细胞淋巴瘤患者。然而,单独的单药治疗不是治愈性的,需要联合治疗。本文全面总结了现代治疗策略和联合治疗。目前尚无针对多发性骨髓瘤的免疫检查点抑制剂获批。尽管 PD-1/PD-L1 抑制剂与免疫调节剂联合最初似乎很有希望,但意外的免疫相关毒性已停止了任何进一步的开发。本文进一步讨论了骨髓瘤和淋巴瘤中的新策略和更有效的联合治疗。

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