PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
复制标题
DOI：
10.1056/nejmoa1411087
复制
发表时间：
2015-01-22
期刊：
影响因子：
--
通讯作者：
Armand P
中科院分区：
文献类型：
--
作者：
Ansell SM;Lesokhin AM;Borrello I;Halwani A;Scott EC;Gutierrez M;Schuster SJ;Millenson MM;Cattry D;Freeman GJ;Rodig SJ;Chapuy B;Ligon AH;Zhu L;Grosso JF;Kim SY;Timmerman JM;Shipp MA;Armand P
临床前研究表明，Reed-Sernberg细胞探索了经典Hodgkin淋巴瘤中逃避免疫检测的程序死亡1（PD-1）途径。 -l2，并通过Janus激酶（JAK） - 信号转录器和转录激活因子（STAT）信号传导促进其诱导。淋巴瘤。
在这项正在进行的研究中，每2周接受了重度治疗的23例继电器或难治性霍奇金的淋巴瘤接受Nivolumab（每公斤每公斤体重3毫克），直到他们完全反应，肿瘤进展或过度毒性毒性毒性效果。
在23名研究患者中，自体干细胞移植后继电器后，有78％的人参加了该研究，并在接收Brentuximab vedotin后的继电器后78％。 ％和22％的患者报告了20例患者（87％），其中有70％的患者和剩余的3例患者（13％）患有稳定的疾病24周的无进展生存率为86％； 2个患者的分析。从10位患者进行预处理肿瘤标本，显示PDL1和PDL2的拷贝数增长以及这些配体的表达增加。
Nivolumab具有实质性的治疗活性和可接受的安全性，可在先前接受治疗的继电器或难治性Hodgkin的淋巴瘤（由Bristol-Myers Squibb等人资助；
Preclinical studies suggest that Reed–Sternberg cells exploit the programmed death 1 (PD-1) pathway to evade immune detection. In classic Hodgkin's lymphoma, alterations in chromosome 9p24.1 increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and promote their induction through Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling. We hypothesized that nivolumab, a PD-1–blocking antibody, could inhibit tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma. In this ongoing study, 23 patients with relapsed or refractory Hodgkin's lymphoma that had already been heavily treated received nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks until they had a complete response, tumor progression, or excessive toxic effects. Study objectives were measurement of safety and efficacy and assessment of the PDL1 and PDL2 (also called CD274 and PDCD1LG2, respectively) loci and PD-L1 and PD-L2 protein expression. Of the 23 study patients, 78% were enrolled in the study after a relapse following autologous stem-cell transplantation and 78% after a relapse following the receipt of brentuximab vedotin. Drug-related adverse events of any grade and of grade 3 occurred in 78% and 22% of patients, respectively. An objective response was reported in 20 patients (87%), including 17% with a complete response and 70% with a partial response; the remaining 3 patients (13%) had stable disease. The rate of progression-free survival at 24 weeks was 86%; 11 patients were continuing to participate in the study. Reasons for discontinuation included stem-cell transplantation (in 6 patients), disease progression (in 4 patients), and drug toxicity (in 2 patients). Analyses of pretreatment tumor specimens from 10 patients revealed copy-number gains in PDL1 and PDL2 and increased expression of these ligands. Reed–Sternberg cells showed nuclear positivity of phosphorylated STAT3, indicative of active JAK-STAT signaling. Nivolumab had substantial therapeutic activity and an acceptable safety profile in patients with previously heavily treated relapsed or refractory Hodgkin's lymphoma. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT01592370.)