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异基因造血干细胞移植治疗霍奇金淋巴瘤中 PD-1 阻断的管理建议:驾驭必要之恶。

Recommendations for managing PD-1 blockade in the context of allogeneic HCT in Hodgkin lymphoma: taming a necessary evil.

机构信息

Université de Lille, Service des Maladies du Sang, Centre Hospitalier Régional Universitaire de Lille, Lille, France.

Dana-Farber Cancer Institute, Boston, MA.

出版信息

Blood. 2018 Jul 5;132(1):9-16. doi: 10.1182/blood-2018-02-811174. Epub 2018 May 2.

Abstract

PD-1 blockade is an effective therapy in relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) who have relapsed after or are ineligible for autologous hematopoietic cell transplantation (HCT). Although single-agent anti-PD-1 monoclonal antibodies (mAb's) are associated with high response rates and durable remissions, available results to date suggest that a large majority of patients will eventually progress on therapy. Many of these patients are potential candidates for allogeneic HCT (allo-HCT) after receiving anti-PD-1 mAb's, and allo-HCT remains for now the only treatment with demonstrated curative potential in this setting. However, initial reports suggested that allo-HCT in this setting may be associated with increased risk of early transplant-related toxicity, likely driven by lingering effects of PD-1 blockade. Furthermore, many patients with R/R cHL who undergo allo-HCT will relapse after transplantation, most often with limited treatment options. Here again, PD-1 blockade appears to yield high response rates, but with an increased risk of attendant immune toxicity. Many questions remain regarding the use of PD-1 blockade before or after allo-HCT, especially in relation to the feasibility, outcome, optimal timing, and method of allo-HCT after PD-1 blockade. Despite the scarcity of prospective data, these questions are unavoidable and must be tackled by clinicians in the routine care of patients with advanced cHL. We provide consensus recommendations of a working group based on available data and experience, in an effort to help guide treatment decisions until more definitive data are obtained.

摘要

PD-1 阻断疗法在复发/难治性(R/R)经典型霍奇金淋巴瘤(cHL)患者中具有显著疗效,这些患者在自体造血细胞移植(HCT)后复发或不适合进行自体 HCT。尽管单药抗 PD-1 单克隆抗体(mAb)与高反应率和持久缓解相关,但迄今为止的可用结果表明,大多数患者最终将在治疗中进展。这些患者中的许多人在接受抗 PD-1 mAb 治疗后可能是同种异体 HCT(allo-HCT)的潜在候选者,而 allo-HCT 仍然是目前在该环境中具有明确治愈潜力的唯一治疗方法。然而,最初的报告表明,allo-HCT 在这种情况下可能与早期移植相关毒性的风险增加相关,这可能是由 PD-1 阻断的持久影响所驱动。此外,许多接受 allo-HCT 的 R/R cHL 患者在移植后会复发,大多数情况下治疗选择有限。在这里,PD-1 阻断似乎也能产生高反应率,但伴随免疫毒性的风险增加。关于 allo-HCT 之前或之后使用 PD-1 阻断的问题仍然存在,特别是关于可行性、结果、最佳时机和 allo-HCT 后 PD-1 阻断的方法。尽管前瞻性数据稀缺,但这些问题是不可避免的,临床医生必须在常规治疗晚期 cHL 患者时解决这些问题。我们基于现有数据和经验提供了工作组的共识建议,以帮助指导治疗决策,直到获得更明确的数据。

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