针对BCL2 Venetoclax在慢性淋巴细胞白血病复发。

文章的细节

引用

复制到剪贴板

罗伯茨啊,戴维斯女士,由此JM,卡尔BS, Puvvada SD, Gerecitano摩根富林明,林·TJ,安德森,棕色的小,Gressick L,黄,邓巴米,朱M,德赛MB, Cerri E, Heitner恩斯赫德年代,Humerickhouse RA, Wierda WG Seymour摩根富林明

针对BCL2 Venetoclax在慢性淋巴细胞白血病复发。

郑传经地中海J。2016年1月28日,374(4):311 - 22所示。doi: 10.1056 / NEJMoa1513257。Epub 2015年12月6日。

PubMed ID

26639348 (在PubMed

]

文摘

背景:新疗法改善结果复发患者的慢性淋巴细胞白血病(CLL),但完全缓解仍然少见。Venetoclax有截然不同的作用机理;目标BCL2,蛋白质中心慢性淋巴细胞白血病细胞的生存。方法:我们进行了一次剂量研究第一阶段的日常口腔venetoclax复发或难治性慢性淋巴细胞白血病患者或小淋巴细胞性淋巴瘤(SLL)来评估安全、药代动力学资料,和有效性。在剂量递增阶段,56个患者接受积极治疗的8个剂量组,范围从150到1200毫克每天。在扩大队列,60额外的患者接受每周逐步过渡剂量高达400毫克每天。这项研究的结果:绝大多数患者已收到多个前治疗,和89%的不良预后的临床或遗传特性。Venetoclax活跃在所有剂量水平。临床肿瘤溶解综合征发生在3的56个病人剂量队列,一人死亡。调整剂量递增计划后,临床肿瘤溶解综合征不发生在任何的60名患者群体扩张。 Other toxic effects included mild diarrhea (in 52% of the patients), upper respiratory tract infection (in 48%), nausea (in 47%), and grade 3 or 4 neutropenia (in 41%). A maximum tolerated dose was not identified. Among the 116 patients who received venetoclax, 92 (79%) had a response. Response rates ranged from 71 to 79% among patients in subgroups with an adverse prognosis, including those with resistance to fludarabine, those with chromosome 17p deletions (deletion 17p CLL), and those with unmutated IGHV. Complete remissions occurred in 20% of the patients, including 5% who had no minimal residual disease on flow cytometry. The 15-month progression-free survival estimate for the 400-mg dose groups was 69%. CONCLUSIONS: Selective targeting of BCL2 with venetoclax had a manageable safety profile and induced substantial responses in patients with relapsed CLL or SLL, including those with poor prognostic features. (Funded by AbbVie and Genentech; ClinicalTrials.gov number, NCT01328626.).

beplay体育安全吗DrugBank数据引用了这篇文章

药物

Venetoclax