Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma
Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma
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DOI：
10.1200/jco.2016.72.1316
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发表时间：
2017-07-01
影响因子：
45.3
通讯作者：
Moskowitz, Craig H.
中科院分区：
文献类型：
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作者：
Chen, Robert;Zinzani, Pier Luigi;Moskowitz, Craig H.
目的Hodgkin Reed-Sternberg 细胞染色体 9p24.1 发生改变，导致程序性死亡配体 1 (PD-L1) 和 PD-L2 过度表达。 Pembrolizumab 是一种程序性死亡 1 阻断抗体，在 I 期测试中对复发或难治性经典霍奇金淋巴瘤 (rrHL) 患者表现出较高的总体缓解率 (ORR)。方法KEYNOTE-087（ClinicalTrials.gov 标识符，NCT02453594）是 Pembrolizumab 在三个队列中的单组 II 期研究 rrHL 患者的比例，根据 (1) 自体干细胞移植 (ASCT) 和随后的 brentuximab vedotin (BV) 后淋巴瘤进展进行定义； (2) 挽救性化疗和 BV，因此因化疗耐药性疾病不适合 ASCT； (3) ASCT，但移植后无 BV。患者每 3 周接受一次 200 mg 派姆单抗治疗。每 12 周评估一次疗效。主要终点是中央审查的 ORR 和安全性。 结果 共有 210 名患者入组并接受治疗（队列 1 69 名、队列 2 81 名、队列 3 60 名）。在分析时，患者平均接受了 13 个治疗周期。根据中央审查，ORR 为 69.0%（95% CI，62.3% 至 75.2%），完全缓解率为 22.4%（95% CI，16.9% 至 28.6%）。按队列划分，队列 1 的 ORR 为 73.9%，队列 2 为 64.2%，队列 3 为 70.0%。31 名患者的缓解时间≥ 6 个月。安全性与之前的 pembrolizumab 研究基本一致。结论 Pembrolizumab 与 rrHL 患者的高缓解率和可接受的安全性相关，为该疾病提供了新的治疗范例。 (C) 2017 年美国临床肿瘤学会
PurposeHodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing.MethodsKEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety.ResultsA total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response >= 6 months. The safety profile was largely consistent with previous pembrolizumab studies.ConclusionPembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease. (C) 2017 by American Society of Clinical Oncology