When is it OK to Stop Anti-Programmed Death 1 Receptor (PD-1) Therapy in Metastatic Melanoma?
When is it OK to Stop Anti-Programmed Death 1 Receptor (PD-1) Therapy in Metastatic Melanoma?
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DOI：
10.1007/s40257-020-00506-2
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发表时间：
2020-02-05
影响因子：
7.3
通讯作者：
Sullivan, Ryan J.
中科院分区：
文献类型：
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作者：
Banks, Lauren B.;Sullivan, Ryan J.
在过去的十年里，随着高效的免疫检查点抑制，特别是抗程序性死亡1受体(PD-1)治疗的发展，转移性黑色素瘤的系统治疗已经发生了革命性的变化。然而，尽管三分之一的患者对单一药物或联合治疗有持久的反应，但最佳治疗时间尚不清楚。确定最佳治疗时间是重要的，因为暴露于抗PD-1治疗会增加发生免疫介导的毒性的风险，这种毒性可能具有显著的发病率，有时甚至是致命的。长期以来，人们一直认为，对大剂量白介素2和ipilimumab完全有效的患者通常在短暂的疗程后保持他们的反应；因此，更好地理解这些数据非常重要，以帮助理解接受抗PD-1治疗的黑色素瘤患者的最佳管理。以抗PD-1为基础的治疗的临床数据和关于治疗持续时间的公布数据表明，患者可能不需要整整两年的抗PD-1治疗，通过进一步了解治疗反应的机制和动力学，毒性风险可能会得到缓解。尽管帮助指导治疗决策的新标记物正在研究中，但仍有必要改进我们的工具，以监测对治疗和疾病活动的反应。
Systemic therapy for metastatic melanoma has been revolutionized over the past decade with the development of highly effective immune checkpoint inhibition, specifically anti-Programmed Death 1 receptor (PD-1) therapy. However, even though one-third of patients will have durable response to single-agent or combination therapy, the optimal duration of therapy is unknown. Identifying the optimal duration of therapy is important, as exposure to anti-PD-1 therapy increases the risk of developing immune-mediated toxicities that can have significant morbidity and are, at times, fatal. It has long been understood that patients with complete responses to high-dose interleukin-2 and ipilimumab typically maintain their responses after a brief treatment course; thus, it is important to better understand the data to help understand the optimal management of melanoma patients treated with anti-PD-1 therapy. The clinical data with anti-PD-1-based therapy and published data on the duration of therapy suggest that patients may not require a full 2 years of anti-PD-1 therapy and that the risk of toxicity may be mitigated by further understanding the mechanisms and kinetics of response to therapy. Although novel markers to help guide therapeutic decision making are under investigation, there is an ongoing need to improve our tools to monitor response to therapy and disease activity.