接受抗程序性死亡-1 治疗转移性黑色素瘤患者的基底细胞癌和鳞状细胞癌的发病率。

Incidence of Basal Cell Carcinoma and Squamous Cell Carcinoma in Patients on Antiprogrammed Cell Death-1 Therapy for Metastatic Melanoma.

机构信息

Department of Dermatology.

Sydney Medical School, The University of Sydney, Sydney, Australia.

出版信息

J Immunother. 2018 Sep;41(7):343-349. doi: 10.1097/CJI.0000000000000237.

DOI:10.1097/CJI.0000000000000237

PMID:29939876

Abstract

Systemic melanoma therapies have the potential to affect basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cuSCC) development. In this study, we aim to compare the incidence of BCC and cuSCC in patients with metastatic melanoma treated with antiprogrammed cell death-1 (anti-PD1), BRAF inhibitor (BRAFi) monotherapy or dabrafenib and trametinib combination therapy (CombiDT) with a group of control patients having similar risk factors. We reviewed the records of melanoma patients on anti-PD1, BRAFi, or CombiDT, and patients from the High-Risk Melanoma Clinic, Westmead Hospital. We also performed an immunohistochemical analysis of BCCs under anti-PD1 compared with controls using PD1, PD-L1, CD3, CD8, and CD20 stains. For the results, in all, 340 patients were included; 82 on anti-PD1, 134 on BRAFi, 69 on CombiDT, and 55 controls. BRAFi had the highest incidence of BCC (12.7%), followed by CombiDT (10.1%) and anti-PD1 (2.4%). The incidence of BCC was significantly lower in patients on anti-PD1 (2.4% vs. 19.4%; P<0.001) compared with controls. Patients on anti-PD1 were 8.54 times less likely to develop BCC than the controls [hazard ratio, 0.117 (95% confidence interval, 0.026-0.526), P=0.005]. BRAFi and CombiDT showed no significant differences in BCC incidence compared with controls. BRAFi had the highest cuSCC incidence (23.9%), followed by anti-PD1 (7.3%) and CombiDT (2.9%). The incidence of cuSCC was significantly higher in patients on BRAFi (23.9% vs. 3.5%; P<0.001) compared with controls, but anti-PD1 and CombiDT showed no differences in cuSCC incidence compared with controls. Immunohistochemistry analysis of 10 BCC from under anti-PD1 and 8 BCC from controls patients showed that while all BCC had negative PD-L1 staining, the percentage of PD1 staining in anti-PD1 group is significantly lower than that of the control group (independent t test, 8% vs. 26%; P<0.001). In conclusion, our study suggests that anti-PD1 therapy decreases the incidence of BCC, as a result of the PD1/PD-L1 blockade. Future studies investigating the role of anti-PD1 in suppressing or treating BCC may be warranted.

摘要

系统黑色素瘤治疗有影响基底细胞癌（BCC）和皮肤鳞状细胞癌（cuSCC）发展的潜力。在这项研究中，我们旨在比较转移性黑色素瘤患者接受抗程序性细胞死亡-1（抗 PD-1）、BRAF 抑制剂（BRAFi）单药或达拉非尼和曲美替尼联合治疗（CombiDT）与一组具有相似危险因素的对照组患者的 BCC 和 cuSCC 发病率。我们回顾了接受抗 PD-1、BRAFi 或 CombiDT 治疗的黑色素瘤患者和韦斯特米德医院高危黑色素瘤诊所的患者的记录。我们还使用 PD-1、PD-L1、CD3、CD8 和 CD20 染色对接受抗 PD-1 治疗的 BCC 与对照组进行了免疫组织化学分析。结果，共纳入 340 例患者；82 例接受抗 PD-1 治疗，134 例接受 BRAFi 治疗，69 例接受 CombiDT 治疗，55 例为对照组。BRAFi 的 BCC 发生率最高（12.7%），其次是 CombiDT（10.1%）和抗 PD-1（2.4%）。与对照组相比，接受抗 PD-1 治疗的患者 BCC 发生率显著降低（2.4%比 19.4%；P<0.001）。与对照组相比，接受抗 PD-1 治疗的患者发生 BCC 的风险降低了 8.54 倍[风险比，0.117（95%置信区间，0.026-0.526），P=0.005]。BRAFi 和 CombiDT 与对照组相比，BCC 发生率无显著差异。BRAFi 的 cuSCC 发生率最高（23.9%），其次是抗 PD-1（7.3%）和 CombiDT（2.9%）。与对照组相比，接受 BRAFi 治疗的患者 cuSCC 发生率显著升高（23.9%比 3.5%；P<0.001），但抗 PD-1 和 CombiDT 与对照组相比，cuSCC 发生率无差异。对 10 例接受抗 PD-1 治疗和 8 例接受对照组治疗的 BCC 患者进行免疫组织化学分析显示，尽管所有 BCC 均为 PD-L1 阴性染色，但抗 PD-1 组的 PD1 染色百分比明显低于对照组（独立 t 检验，8%比 26%；P<0.001）。总之，我们的研究表明，抗 PD-1 治疗通过 PD1/PD-L1 阻断降低了 BCC 的发生率。未来研究可能需要调查抗 PD-1 抑制或治疗 BCC 的作用。