Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Center for Melanoma, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA.
Am J Clin Dermatol. 2020 Jun;21(3):313-321. doi: 10.1007/s40257-020-00506-2.
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.
过去十年，随着高效免疫检查点抑制剂的发展，特别是抗程序性死亡受体 1（PD-1）治疗的发展，转移性黑色素瘤的全身治疗发生了革命性变化。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，但治疗的最佳持续时间尚不清楚。确定治疗的最佳持续时间很重要，因为接触抗 PD-1 治疗会增加发生免疫介导的毒性的风险，这些毒性可能会导致严重的发病率，有时甚至是致命的。人们早就知道，对高剂量白细胞介素-2 和伊匹单抗有完全反应的患者通常在短暂的治疗后仍能保持反应；因此，重要的是要更好地了解数据，以帮助了解接受抗 PD-1 治疗的黑色素瘤患者的最佳管理。基于抗 PD-1 治疗的临床数据和已发表的治疗持续时间数据表明，患者可能不需要进行整整 2 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，可能会减轻毒性风险。尽管正在研究有助于指导治疗决策的新型标志物，但仍需要改进我们的工具来监测治疗反应和疾病活动。
