A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma.
A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma.
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对复发或难治性淋巴瘤中的组蛋白脱乙酰基酶抑制剂的2阶段研究。
DOI：
10.1111/bjh.14698
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发表时间：
2017-08
影响因子：
6.5
通讯作者：
Younes A
中科院分区：
文献类型：
--
作者：
Batlevi CL;Crump M;Andreadis C;Rizzieri D;Assouline SE;Fox S;van der Jagt RHC;Copeland A;Potvin D;Chao R;Younes A
组蛋白脱乙酰酶(HDAC)的失控在滤泡性淋巴瘤(FL)和弥漫性大B细胞淋巴瘤(DLBCL)的发病机制中起重要作用。莫西替诺是一种同型选择性HDAC抑制剂，可诱导几种癌症中乙酰化组蛋白的积聚、细胞周期停滞和细胞凋亡。这项2期研究评估了莫西替酯在复发/难治(R/R)DLBCL和FL患者中的作用。72例患者接受莫西替酯治疗(起始剂量：70-110 mg，tiw，4周为一周期)。总有效率(95%CI)：DLBCL组(n=41)为18.9%(7.2，32.2)，FL组(n=31)为11.5%(1.7，20.7)。反应是持久的(≥90天，7/10)。总体而言，在DLBCL和FL队列中，54.1%和73.1%的患者分别从莫西替酯获得临床益处(缓解或稳定疾病)。DLBCL和FL的无进展生存期分别为1.8~22.8个月和11.8~26.3个月。最常见的不良反应是乏力(75.0%)、恶心(69.4%)和腹泻(61.1%)。尽管莫西替诺在R/R DLBCL和FL中的单药活性有限，但临床受益的患者可以长期控制疾病。安全状况是可以接受的。这种药物类别需要进一步的研究，包括确定更有可能对这种药物有反应的患者，或与其他药物联合使用。
Deregulation of histone deacetylase (HDAC) is important in the pathogenesis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Mocetinostat, an isotype-selective HDAC inhibitor, induces accumulation of acetylated histones, cell cycle arrest and apoptosis in several cancers. This phase 2 study evaluated mocetinostat in patients with relapsed/refractory (R/R) DLBCL and FL. Seventy-two patients received mocetinostat (starting doses: 70–110 mg TIW, 4-week cycles). The best overall response rate (95% CI) was 18.9% (7.2, 32.2) for the DLBCL cohort (n = 41), and 11.5% (1.7, 20.7) for the FL cohort (n = 31). Responses were durable (≥90 days in 7 of 10 responses). Overall, 54.1% and 73.1% of patients derived clinical benefit (response or stable disease) from mocetinostat in the DLBCL and FL cohorts, respectively. Progression-free survival ranged from 1.8 to 22.8 months and 11.8 to 26.3 months in responders with DLBCL and FL, respectively. The most frequent treatment-related adverse events were fatigue (75.0%), nausea (69.4%) and diarrhoea (61.1%). Although mocetinostat had limited single-agent activity in R/R DLBCL and FL, patients with clinical benefit had long-term disease control. The safety profile was acceptable. This drug class warrants further investigation, including identifying patients more likely to respond to this agent, or in combination with other agents.
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影响因子：
6.1
作者：
Boumber Y;Younes A;Garcia-Manero G
通讯作者：
Garcia-Manero G
影响因子：
6.5
作者：
Ogura M;Ando K;Suzuki T;Ishizawa K;Oh SY;Itoh K;Yamamoto K;Au WY;Tien HF;Matsuno Y;Terauchi T;Yamamoto K;Mori M;Tanaka Y;Shimamoto T;Tobinai K;Kim WS
通讯作者：
Kim WS
影响因子：
30.8
作者：
Bereshchenko, OR;Gu, W;Dalla-Favera, R
通讯作者：
Dalla-Favera, R
影响因子：
8
作者：
Chauchereau, A;Mathieu, M;Harel-Bellan, A
通讯作者：
Harel-Bellan, A
影响因子：
45.3
作者：
O'Connor, OA;Heaney, ML;Kelly, WK
通讯作者：
Kelly, WK