PURPOSE To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS). PATIENTS AND METHODS CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria. RESULTS Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature. CONCLUSION Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.

中文翻译：

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派姆单抗治疗复发性和难治性蕈样肉芽肿和塞扎里综合征：一项多中心 II 期研究


目的 评估派姆单抗对晚期复发或难治性蕈样肉芽肿 (MF) 或塞扎里综合征 (SS) 患者的疗效。患者和方法 CITN-10 是一项单组、多中心 II 期试验，受试者为 24 名晚期 MF 或 SS 患者。患者每 3 周接受 2 mg/kg 派姆单抗治疗，治疗时间长达 24 个月。主要终点是根据全球共识缓解标准得出的总体缓解率。结果 患者患有晚期疾病（24 名患者中的 23 名患者为 IIB 至 IV 期 MF/SS），并且接受了中位数为 4 次的先前全身治疗的大量预处理。总体答复率为 38%，其中有 2 名完全答复和 7 名部分答复。在九名有反应的患者中，通过修改后的严重程度加权评估工具，六名患者的皮肤病改善了 90% 或更多，八名患者在最后一次随访中持续有反应。中位缓解持续时间尚未达到，中位缓解随访时间为 58 周。免疫相关不良事件导致四名患者停止治疗。 53% 的 SS 患者出现短暂性红皮病和瘙痒恶化。这种皮肤耀斑反应并未导致任何患者停止治疗。耀斑反应与 Sézary 细胞上的高 PD-1 表达相关，但与随后的临床反应或缺乏反应无关。治疗反应与 PD-L1 表达、总突变负荷或干扰素-γ 基因表达特征无关。结论 Pembrolizumab 在晚期 MF/SS 患者中表现出显着的抗肿瘤活性、持久的反应和良好的安全性。