Chen Robert, Zinzani Pier Luigi, Fanale Michelle A, Armand Philippe, Johnson Nathalie A, Brice Pauline, Radford John, Ribrag Vincent, Molin Daniel, Vassilakopoulos Theodoros P, Tomita Akihiro, von Tresckow Bastian, Shipp Margaret A, Zhang Yinghua, Ricart Alejandro D, Balakumaran Arun, Moskowitz Craig H
Robert Chen, City of Hope National Medical Center, Duarte, CA; Pier Luigi Zinzani, University of Bologna, Bologna, Italy; Michelle A. Fanale, The University of Texas MD Anderson Cancer Center, Houston, TX; Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Nathalie A. Johnson, Jewish General Hospital, Montreal, Canada; Pauline Brice, Hôpital Saint-Louis, Paris; Vincent Ribrag, Institut Gustave Roussy, Villejuif, France; John Radford, The University of Manchester and Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom; Daniel Molin, Uppsala University, Uppsala, Sweden; Theodoros P. Vassilakopoulos, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece; Akihiro Tomita, Nagoya University Graduate School of Medicine, Nagoya, Japan; Bastian von Tresckow, University Hospital Cologne, Cologne, Germany; Yinghua Zhang, Alejandro D. Ricart, and Arun Balakumaran, Merck, Kenilworth, NJ; Craig H. Moskowitz, Memorial Sloan Kettering Cancer Center, New York, NY.
J Clin Oncol. 2017 Jul 1;35(19):2125-2132. doi: 10.1200/JCO.2016.72.1316. Epub 2017 Apr 25.
Purpose Hodgkin 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. Methods KEYNOTE-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. Results A 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. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.
目的 霍奇金-里德-斯腾伯格细胞存在9号染色体p24.1区域的改变，导致程序性死亡配体1（PD-L1）和PD-L2过表达。帕博利珠单抗是一种程序性死亡1阻断抗体，在I期试验中，其在复发或难治性经典霍奇金淋巴瘤（rrHL）患者中显示出较高的总缓解率（ORR）。方法 KEYNOTE-087（ClinicalTrials.gov标识符，NCT02453594）是一项单臂II期研究，对三组rrHL患者使用帕博利珠单抗，这三组患者根据淋巴瘤进展情况定义如下：（1）自体干细胞移植（ASCT）及随后的维布妥昔单抗（BV）治疗后；（2）挽救性化疗及BV治疗后，因化疗耐药疾病而不符合ASCT条件；（3）ASCT后，但移植后未使用BV。患者每3周接受一次200mg帕博利珠单抗治疗。每12周评估一次缓解情况。主要终点为中心审查的ORR和安全性。结果 共纳入210例患者并接受治疗（队列1中的69例，队列2中的81例，队列3中的60例）。在分析时，患者接受治疗的中位周期数为13个。根据中心审查，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%）。按队列分析，队列1的ORR为73.9%，队列2为64.2%，队列3为70.0%。31例患者缓解持续时间≥6个月。安全性特征与既往帕博利珠单抗研究基本一致。结论 帕博利珠单抗在rrHL患者中具有高缓解率和可接受的安全性特征，为该疾病提供了一种新的治疗模式。
