Joseph Richard W, Cappel Mark, Tzou Katherine, Bagaria Sanjay, Gilstrap Cheryl, Swaika Abhisek, Jambusaria-Pahlajani Anokhi
aDivision of Medical Oncology Departments of bDermatology cRadiation Oncology dGeneral Surgery, Mayo Clinic Florida, Jacksonville, Florida, USA.
Melanoma Res. 2016 Aug;26(4):409-12. doi: 10.1097/CMR.0000000000000247.
Checkpoint blockade inhibitors have revolutionized the treatment of metastatic melanoma. Despite the success of these agents in improving the overall survival of patients with metastatic melanoma, not all patients achieve clinical benefit, leaving room for improvement. The presence of cutaneous metastases in patients with metastatic melanoma provides the unique opportunity to treat the cutaneous lesions with a local modality while simultaneously treating systemic disease with systemic therapy. Herein, we describe the treatment of two patients with both in-transit and metastatic melanoma with the combination of the topical toll-like receptor 7 agonist imiquimod with systemic ipilimumab. Both patients appeared to have progressed and developed new cutaneous and systemic metastases while on single agent ipilimumab only to respond when started on topical imiquimod. Both patients tolerated the combination of imiquimod and ipilimumab without serious adverse events, and both patients had excellent clinical responses. These cases provide a proof of principle of the possibility of the combination of toll-like receptor 7 agonists with immune checkpoint blockade inhibitors.
检查点阻断抑制剂彻底改变了转移性黑色素瘤的治疗方式。尽管这些药物在提高转移性黑色素瘤患者的总生存率方面取得了成功,但并非所有患者都能获得临床益处,仍有改进的空间。转移性黑色素瘤患者出现皮肤转移,为采用局部治疗方法治疗皮肤病变同时采用全身治疗方法治疗全身疾病提供了独特的机会。在此,我们描述了两名患有移行性和转移性黑色素瘤的患者,采用局部 toll 样受体 7 激动剂咪喹莫特与全身应用伊匹木单抗联合治疗。两名患者在仅接受单药伊匹木单抗治疗时似乎都出现了病情进展并出现了新的皮肤和全身转移,而在开始使用局部咪喹莫特治疗后才有反应。两名患者均耐受咪喹莫特和伊匹木单抗的联合治疗,未出现严重不良事件,且两名患者均有出色的临床反应。这些病例为 toll 样受体 7 激动剂与免疫检查点阻断抑制剂联合使用的可能性提供了原理证明。