目的：探讨PD-1抗体对比高剂量干扰素在ⅡB-ⅢD期黑色素瘤患者术后辅助治疗中的疗效及安全性。方法：回顾性收集2013 年9 月至2022 年9 月期间在南京大学医学院附属楼医院收治的ⅡB-ⅢD期皮肤和肢端黑色素瘤患者的临床资料。所有患者术后均接受了高剂量干扰素（HDI）或PD-1 抗体辅助治疗。通过Kaplan-Meier 法行单因素生存分析并绘制生存曲线， Log-Rank 法分析评估组间无复发生存期（RFS）、无远处转移生存期（DMFS）以及总生存期（OS）差异是否有统计学意义，单因素和多因素Cox 回归分析判断影响患者预后的因素。结果：本研究共纳入91 例患者，中位随访时间为31.0个月。HDI 组和PD-1抗体组的mRFS 分别为29.2 个月和32.3 个月，差异无统计学意义[HR=0.90, 95%CI（0.50，1.64）；P=0.736]。HDI 组的mDMFS 和mOS分别为36.0个月和109.2个月，而PD-1抗体组均未达到（均P>0.05）。两组最常见的首次远处转移部位均是肺，并且在任何部位远处转移的发生率均无统计学差异（P>0.05）。通过单因素Cox 分析，相比于PD-1抗体，HDI 可以降低BRAFV600E/K突变的患者的远处转移风险[HR=10.03, 95%CI（1.10，91.35）；P=0.041]。亚组分析结果显示，在皮肤和肢端黑色素瘤中，HDI 组和PD-1单抗组的RFS 差异无统计学意义（均P>0.05）。HDI 组和PD-1抗体组不良反应发生率分别为83.3%和79.1%，多数为1或2级。两组均未发生与不良反应有关的死亡事件。结论：本研究中，PD-1抗体与HDI辅助治疗恶性黑色素瘤的临床疗效和安全性差异均无统计学意义；BRAFV600E/K突变的患者可能从HDI中获益更多；仍需大量前瞻性研究进一步探索亚洲人群黑色素瘤患者的最佳辅助治疗方案。

Objective: To explore the efficacy and safety of PD-1 antibody versus high-dose interferon in the adjuvant treatment of stage ⅡB-ⅢD melanoma patients after surgery. Methods: Clinical data of patients with stage ⅡB-ⅢD cutaneous and acral melanoma admitted into Nanjing Drum Tower Hospital, the affiliated hospital of Nanjing University Medical School between September 2013 and September 2022 were retrospectively collected. All patients received high-dose interferon (HDI) or PD-1 antibody as adjuvant therapy after surgery. Univariate survival analysis was performed and survival curves were plotted by the Kaplan-Meier method; Log-Rank method was used to analyze and assess whether the differences in RFS, DMFS, and OS between the groups were statistically significant, and prognostic factors were evaluated by univariate and multivariate Cox regression. Results: A total of 91 patients were enrolled in this study with a median follow-up of 31.0 months. The median RFS was 29.2 and 32.3 months in the HDI group and the PD-1 antibody group, respectively, and the difference was not statistically significant (HR=0.90, 95%CI [0.50, 1.64]; P=0.736). The median DMFS and the median OS in the HDI group were 36.0 and 109.2 months respectively, and neither was reached in the PD-1 antibody group (both P>0.05). The most common site of first distant metastasis in both groups was the lung, and there was no statistically significant difference in the incidence of distant metastasis at any site (P>0.05). By univariate Cox analysis, compared with PD-1, antibody HDI reduced the risk of distant metastasis in patients with BRAFV600E/K mutations (HR=10.03, 95% CI [1.10, 91.35]; P=0.041). Subgroup analyses showed that in patients with cutaneous and acral melanoma, the difference in RFS between the HDI group and the PD-1 antibody group was not statistically significant (both P>0.05). The incidence of adverse reactions in the HDI group and the PD-1 antibody group was 83.3% and 79.1%, respectively, most of which were grade 1 or 2. No deaths related to adverse reactions occurred in both groups. Conclusion: In this study, there was no statistically significant difference in clinical efficacy and safety between PD-1 antibody and HDI adjuvant therapy for malignant melanoma patients. Patients with BRAFV600E/K mutations may benefit more from HDI. Numerous prospective studies are needed to further explore the optimal adjuvant treatment options for melanoma patients in Asian populations.

国家自然科学基金项目（No.81872484，No.82073365）；江苏省社会发展项目（No.BE2019605）