Immunotherapy of Lymphoma and Myeloma: Facts and Hopes.
Immunotherapy of Lymphoma and Myeloma: Facts and Hopes.
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DOI：
10.1158/1078-0432.ccr-17-0539
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发表时间：
2018-03-01
期刊：
影响因子：
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通讯作者：
Lesokhin AM
中科院分区：
文献类型：
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作者：
Pianko MJ;Moskowitz AJ;Lesokhin AM
免疫检查点阻断已经推动了现代肿瘤学的革命，并且在实体瘤和血液恶性肿瘤中正在进行免疫检查点抑制剂的稳健药物开发。在经典霍奇金淋巴瘤（cHL）和非霍奇金淋巴瘤（NHL）的几种变体中，对使用nivolumab或pembrolizumab的程序性细胞死亡1（PD-1）阻断的高应答率揭示了对这种方法的内在生物学敏感性，并且正在进行的工作正在探索与cHL和NHL中的免疫检查点抑制剂的组合。还有初步数据表明PD-1抑制剂与免疫调节药物联合治疗多发性骨髓瘤（MM）的抗肿瘤疗效，新型单克隆抗体治疗对肿瘤微环境的影响可能与检查点阻断产生协同作用。尽管免疫检查点抑制剂通常耐受性良好，但临床医生在使用这些药物治疗患者时必须谨慎并保持警惕，以确定免疫相关毒性并预防治疗相关的发病率和死亡率。自体干细胞移植是治疗恶性血液病的有用工具，并有可能作为使用免疫检查点抑制剂的平台。在同种异体干细胞移植前后，与使用PD-1抑制剂相关的移植物抗宿主病（GVHD）风险已出现一个重要的安全性信号。我们的目标是讨论迄今为止在淋巴恶性肿瘤患者中使用免疫检查点抑制剂的已知事实，并讨论我们希望在未来扩大免疫治疗对患者的益处。
Immune checkpoint blockade has driven a revolution in modern oncology, and robust drug development of immune checkpoint inhibitors is underway in both solid tumors and hematologic malignancies. High response rates to programmed cell death 1 (PD-1) blockade using nivolumab or pembrolizumab in classical Hodgkin lymphoma (cHL) and several variants of non-Hodgkin lymphoma (NHL) revealed an intrinsic biologic sensitivity to this approach, and work is ongoing exploring combinations with immune checkpoint inhibitors in both cHL and NHL. There are also preliminary data suggesting antitumor efficacy of PD-1 inhibitors used in combination with immunomodulatory drugs in multiple myeloma (MM), and effects of novel monoclonal antibody therapies on the tumor microenvironment may lead to synergy with checkpoint blockade. Although immune checkpoint inhibitors are generally well-tolerated, clinicians must use caution and remain vigilant when treating patients with these agents in order to identify immune related toxicities and prevent treatment-related morbidity and mortality. Autologous stem cell transplant is a useful tool for treatment of hematologic malignancies and has potential as a platform for use of immune checkpoint inhibitors. An important safety signal has emerged surrounding the risk of graft-versus-host-disease (GVHD) associated with use of PD-1 inhibitors before and after allogeneic stem cell transplant. We aim to discuss the facts known to date in the use of immune checkpoint inhibitors for patients with lymphoid malignancies, and discuss our hopes for expanding the benefits of immunotherapy to patients in the future.