Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for ≥ 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses. Results Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of ≥ 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis. Conclusion Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a cure for some patients. The mechanisms underlying durable CR require further investigation.

中文翻译：

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转移性黑色素瘤患者停用派姆单抗后的持久完全缓解

目的 Pembrolizumab 在转移性黑色素瘤中提供持久的抗肿瘤活性，包括约 15% 的患者的完全缓解 (CR)。关于 CR 的潜在预测因素和 CR 后帕博利珠单抗停药后患者处置的数据有限。我们描述了在 KEYNOTE-001 研究（ClinicalTrials.gov 标识符：NCT01295827）中使用派姆单抗获得 CR 的患者的基线特征和长期随访。患者和方法 患有易普利姆玛初治或接受过治疗的晚期/转移性黑色素瘤患者接受帕博利珠单抗的三种剂量方案之一。接受 pembrolizumab ≥ 6 个月且至少两次治疗超过确认 CR 的符合条件的患者可以停止治疗。根据实体瘤 1.1 版中的中央反应评估标准，每 12 周评估一次反应。对于这个分析，CR 是根据研究者评估、免疫相关反应标准定义的，并且使用单变量和多变量分析评估 CR 的潜在预测因子。结果 在 655 名接受治疗的患者中，105 名 (16.0%) 在中位随访 43 个月后达到 CR。在数据截止时，92 名患者 (87.6%) 获得了 CR，从第一次 CR 开始的中位随访时间为 30 个月。14 名 (13.3%) 患者继续接受治疗的中位时间≥ 40 个月。91 名患者 (86.7%) 停用派姆单抗，其中 67 名 (63.8%) 在没有额外抗癌治疗的情况下继续观察。从 CR 开始的 24 个月无病生存率在所有 105 名 CR 患者中为 90.9%，在 67 名在 CR 后停用派姆单抗进行观察的患者中为 89.9%。通过单变量分析，肿瘤大小和程序性死亡配体 1 状态是与 CR 独立相关的基线因素。结论 转移性黑色素瘤患者停用帕博利珠单抗后可获得持久的完全缓解，中位随访约 2 年后复发率低，为部分患者提供治愈的希望。持久 CR 的机制需要进一步研究。