Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial.
Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial.
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DOI：
10.1200/jco.2017.76.0793
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发表时间：
2018-05-10
期刊：
影响因子：
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通讯作者：
Ansell SM
中科院分区：
文献类型：
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作者：
Armand P;Engert A;Younes A;Fanale M;Santoro A;Zinzani PL;Timmerman JM;Collins GP;Ramchandren R;Cohen JB;De Boer JP;Kuruvilla J;Savage KJ;Trneny M;Shipp MA;Kato K;Sumbul A;Farsaci B;Ansell SM
导致程序性死亡-1配体过表达的遗传改变在经典型霍奇金淋巴瘤（cHL）中几乎是普遍的。Nivolumab是一种程序性死亡-1检查点抑制剂，在来自Nivolumab治疗cHL的CheckMate 205研究的三个队列之一的初始分析中，证明了对自体造血细胞移植（auto-HCT）后复发性/难治性cHL的疗效。在此，我们在对所有三个队列进行延长随访后评估安全性和有效性。这项多中心、单组、II期研究按治疗史将auto-HCT治疗失败后复发性/难治性cHL患者入组队列：维布妥昔单抗（BV）初治（队列A）、auto-HCT后接受BV（队列B）和auto-HCT前和/或后接受BV（队列C）。所有患者每2周一次接受nivolumab 3 mg/kg，直至疾病进展/不可接受的毒性。主要终点是独立放射学审查委员会评估的客观缓解率。总体而言，243例患者接受了治疗;队列A中63例，队列B中80例，队列C中100例。在中位随访18个月后，40%的患者继续接受治疗。总体客观缓解率为69%（95% CI，63%-75%），每个队列的客观缓解率为65%-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例既往接受常规疾病进展治疗的患者中，61%的可评价患者的靶肿瘤负荷稳定或进一步降低。最常见的3 - 4级药物相关不良事件为脂肪酶升高（5%）、中性粒细胞减少（3%）和ALT升高（3%）。发生了29例死亡;认为均与治疗无关。随着随访时间的延长，对nivolumab的反应频繁且持久。纳武利尤单抗似乎在广泛的复发性/难治性cHL患者中具有良好的安全性特征和长期获益。
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. 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. 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. 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.