Philippe Armand and Margaret A. Shipp, Dana-Farber Cancer Institute, Boston, MA; Andreas Engert, University Hospital of Cologne, Cologne, Germany; Anas Younes, Memorial Sloan Kettering Cancer Center, New York, NY; Michelle Fanale, University of Texas MD Anderson Cancer Center, Houston, TX; Armando Santoro, Humanitas Cancer Center, Humanitas University, Milan; Pier Luigi Zinzani, Institute of Hematology "L. e A. Seràgnoli," University of Bologna, Bologna, Italy; John M. Timmerman, University of California Los Angeles Medical Center, Los Angeles, CA; Graham P. Collins, Oxford Cancer and Haematology Centre, Churchill Hospital, Oxford, United Kingdom; Radhakrishnan Ramchandren, Barbara Ann Karmanos Cancer Institute, Detroit, MI; Jonathon B. Cohen, Winship Cancer Institute, Emory University, Atlanta, GA; Jan Paul De Boer, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands, on behalf of Lunenburg Lymphoma Phase I/II Consortium; John Kuruvilla, University of Toronto and Princess Margaret Cancer Centre, Toronto, Ontario; Kerry J. Savage, BC Cancer Agency, Vancouver, British Columbia, Canada; Marek Trneny, Charles University, General Hospital in Prague, Prague, Czech Republic; Kazunobu Kato, Anne Sumbul, and Benedetto Farsaci, Bristol-Myers Squibb, Princeton, NJ; and Stephen M. Ansell, Mayo Clinic, Rochester, MN.
J Clin Oncol. 2018 May 10;36(14):1428-1439. doi: 10.1200/JCO.2017.76.0793. Epub 2018 Mar 27.
Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee. Results Overall, 243 patients were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median follow-up of 18 months, 40% continued to receive treatment. The objective response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort. Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3 months), and median progression-free survival was 14.7 months (95% CI, 11.3 to 18.5 months). Of 70 patients treated past conventional disease progression, 61% of those evaluable had stable or further reduced target tumor burdens. The most common grade 3 to 4 drug-related adverse events were lipase increases (5%), neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were considered treatment related. Conclusion With extended follow-up, responses to nivolumab were frequent and durable. Nivolumab seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.
目的：导致程序性死亡-1 配体过度表达的遗传改变在经典霍奇金淋巴瘤（cHL）中几乎普遍存在。纳武单抗是一种程序性死亡-1 检查点抑制剂，在最初分析来自 CheckMate 205 研究nivolumab 用于 cHL 的三个队列之一时，在自体造血细胞移植（auto-HCT）后复发/难治性 cHL 中显示出疗效。在这里，我们评估了所有三个队列的扩展随访后的安全性和疗效。
方法：这项多中心、单臂、二期研究按治疗史将自体造血细胞移植治疗失败后复发/难治性 cHL 患者纳入三个队列：brentuximab vedotin（BV）初治（队列 A）、自体造血细胞移植后接受 BV（队列 B）和自体造血细胞移植前和/或后接受 BV（队列 C）。所有患者接受nivolumab 3 mg/kg，每 2 周一次，直至疾病进展/无法接受毒性。主要终点是独立放射学审查委员会评估的客观缓解率。
结果：共有 243 例患者接受治疗；队列 A 63 例，队列 B 80 例，队列 C 100 例。中位随访 18 个月后，40%的患者仍在接受治疗。总体客观缓解率为 69%（95%CI，63%至 75%），每个队列为 65%至 73%。总体而言，中位缓解持续时间为 16.6 个月（95%CI，13.2 至 20.3 个月），中位无进展生存期为 14.7 个月（95%CI，11.3 至 18.5 个月）。在 70 例接受常规疾病进展治疗的患者中，61%的可评估患者的靶肿瘤负荷稳定或进一步降低。最常见的 3 级至 4 级与药物相关的不良事件为脂肪酶升高（5%）、中性粒细胞减少（3%）和丙氨酸转氨酶升高（3%）。共发生 29 例死亡；均与治疗无关。
结论：随着随访时间的延长，纳武单抗的反应频繁且持久。纳武单抗似乎与广泛复发/难治性 cHL 患者的有利安全性特征和长期获益相关。
Zhonghua Xue Ye Xue Za Zhi. 2025-4-14
CPT Pharmacometrics Syst Pharmacol. 2017-1
J Clin Oncol. 2016-8-10
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