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在接受异基因细胞移植的淋巴恶性肿瘤患者中使用检查点抑制剂:综述。

Use of checkpoint inhibitors in patients with lymphoid malignancies receiving allogeneic cell transplantation: a review.

机构信息

Department of Hematology, University Hospital Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain.

Laboratory of Experimental Hematology, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.

出版信息

Bone Marrow Transplant. 2021 Aug;56(8):1784-1793. doi: 10.1038/s41409-021-01268-z. Epub 2021 Mar 19.

Abstract

Monoclonal antibodies against checkpoint receptors or its ligands have demonstrated high response rates and durable remissions in patients with relapsed Hodgkin lymphoma (HL) and other lymphoid malignancies. However, most patients will eventually progress on therapy and may benefit from further treatments including allogenic hematopoietic cell transplantation (allo-HCT). Furthermore, the use of checkpoint inhibitors (CPI) has emerged as a treatment option for patients relapsing after allo-HCT. The immune effects of the checkpoint blockade leading to a T-cell activation have raised some concerns on the safety of these therapies used either before or after allo-HCT, due to the potential risk of graft-versus-host disease (GVHD). Furthermore, CPI might also induce other immune toxicities, that can affect almost any organ, as a result of the dysregulation on the immune system balance. This review aims to focus on the evidence behind the use of CPI in patients with lymphoma who undergo allo-HCT. We summarize the clinical data generated to date about the use of CPI in HL and other lymphoid malignancies, the mechanisms of checkpoint inhibition in the context of allo-HCT as well as the clinical and biological observations of different GVHD prophylaxis in this setting. Furthermore, we discuss the evidence from retrospective series and early clinical trials on the feasibility and safety of the use of CPI in patients who relapsed after allo-HCT.

摘要

针对检查点受体或其配体的单克隆抗体已在复发霍奇金淋巴瘤(HL)和其他淋巴恶性肿瘤患者中显示出高缓解率和持久缓解。然而,大多数患者最终会在治疗中进展,并可能受益于进一步的治疗,包括同种异体造血细胞移植(allo-HCT)。此外,检查点抑制剂(CPI)的使用已成为 allo-HCT 后复发患者的治疗选择。检查点阻断导致 T 细胞激活的免疫作用引起了人们对这些在 allo-HCT 之前或之后使用的疗法的安全性的一些关注,因为存在移植物抗宿主病(GVHD)的潜在风险。此外,CPI 还可能引发其他免疫毒性,由于免疫系统平衡失调,这些毒性几乎可以影响任何器官。这篇综述旨在重点关注在接受 allo-HCT 的淋巴瘤患者中使用 CPI 的证据。我们总结了迄今为止关于 CPI 在 HL 和其他淋巴恶性肿瘤中的使用的临床数据,allo-HCT 背景下检查点抑制的机制以及在这种情况下不同 GVHD 预防的临床和生物学观察。此外,我们还讨论了来自回顾性系列和早期临床试验的证据,这些证据涉及在 allo-HCT 后复发的患者中使用 CPI 的可行性和安全性。

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