Randomized, Single-Blind, Multicenter Phase II Study of Two Doses of Imetelstat in Relapsed or Refractory Myelofibrosis

医学 骨髓纤维化 内科学 不利影响 胃肠病学 耐火材料(行星科学) 临床研究阶段 临床试验 外科 骨髓 物理 天体生物学
作者
John Mascarenhas,Rami S. Komrokji,Francesca Palandri,Bruno Martino,Dietger Niederwieser,Andreas Reiter,Bart L. Scott,Maria R. Baer,Ronald Hoffman,Olatoyosi Odenike,Alessandro M. Vannucchi,Jacqueline Bussolari,Eugene Zhu,Esther Rose,Laurie Sherman,Souria Dougherty,Libo Sun,Fei Huang,Ying Wan,Faye Feller
出处
期刊:Journal of Clinical Oncology [Lippincott Williams & Wilkins]
卷期号:39 (26): 2881-2892 被引量:79
标识
DOI:10.1200/jco.20.02864
摘要

PURPOSE Patients with myelofibrosis who are relapsed or refractory (R/R) to Janus-associated kinase inhibitors (JAKis) have poor clinical outcomes including dismal overall survival (OS) that ranges between 13 and 16 months. Imetelstat, a telomerase inhibitor, was evaluated in patients with intermediate-2 or high-risk myelofibrosis R/R to JAKi in a phase II multicenter study (ClinicalTrials.gov identifier: NCT02426086 ). PATIENTS AND METHODS Patients were randomly assigned to receive either imetelstat 9.4 mg/kg or 4.7 mg/kg intravenous once every 3 weeks. Spleen response (≥ 35% spleen volume reduction) and symptom response (≥ 50% reduction in total symptom score) rates at week 24 were coprimary end points. Secondary end points included OS and safety. RESULTS Study enrollment was closed early, and patients treated with 4.7 mg/kg were permitted to continue treatment with 9.4 mg/kg. At week 24, spleen and symptom response rates were 10.2% and 32.2% in the 9.4-mg/kg arm and 0% and 6.3% in the 4.7-mg/kg arm. Treatment with imetelstat 9.4 mg/kg led to a median OS of 29.9 months and bone marrow fibrosis improvement in 40.5% and variant allele frequency reduction of driver mutations in 42.1% of evaluable patients. Fibrosis improvement and variant allele frequency reduction correlated with OS. Target inhibition was demonstrated by reduction of telomerase activity and human telomerase reverse transcriptase level and correlated with spleen response, symptom response, and OS. Most common adverse events on both arms were grade 3 or 4 reversible cytopenias. CONCLUSION In this phase II study of two imetelstat doses, 9.4 mg/kg once every 3 weeks demonstrated clinical benefits in symptom response rate, with an acceptable safety profile for this poor-risk JAKi R/R population. Biomarker and bone marrow fibrosis assessments suggested selective effects on the malignant clone. A confirmatory phase III study is currently underway.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
猴子大王666完成签到,获得积分10
1秒前
搜集达人应助恍若采纳,获得10
1秒前
天天快乐应助周小鱼采纳,获得10
2秒前
miao发布了新的文献求助10
2秒前
小丹发布了新的文献求助10
2秒前
科研通AI2S应助Jeffery426采纳,获得10
2秒前
123完成签到,获得积分10
3秒前
4秒前
朱朱完成签到,获得积分10
4秒前
过时的小凝完成签到,获得积分10
4秒前
动漫大师发布了新的文献求助10
5秒前
善学以致用应助叶伟帮采纳,获得10
6秒前
852应助叶伟帮采纳,获得10
6秒前
爆米花应助ccalvintan采纳,获得10
6秒前
科研通AI5应助叶伟帮采纳,获得10
6秒前
希望天下0贩的0应助Jeremy采纳,获得10
6秒前
6秒前
7秒前
科研通AI5应助zengyiqiao采纳,获得10
7秒前
斯文败类应助易方采纳,获得10
8秒前
迷人冥完成签到 ,获得积分10
8秒前
所所应助czy采纳,获得10
9秒前
卷筒洗衣机完成签到,获得积分10
10秒前
揽月yue应助shuiwuming采纳,获得10
10秒前
周小鱼发布了新的文献求助10
10秒前
奉年完成签到,获得积分10
11秒前
我要发sci应助碧蓝一兰采纳,获得10
11秒前
动漫大师发布了新的文献求助10
11秒前
zjq完成签到,获得积分10
11秒前
Ava应助凌晨采纳,获得10
11秒前
12秒前
一叶给一叶的求助进行了留言
12秒前
费雪卉发布了新的文献求助10
13秒前
DAI完成签到,获得积分10
13秒前
14秒前
传奇3应助miao采纳,获得10
14秒前
木子成发布了新的文献求助10
15秒前
小葵发布了新的文献求助10
15秒前
幽默亦旋完成签到 ,获得积分10
16秒前
彭于晏应助糊涂塌客采纳,获得10
18秒前
高分求助中
Technologies supporting mass customization of apparel: A pilot project 600
Introduction to Strong Mixing Conditions Volumes 1-3 500
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
China Gadabouts: New Frontiers of Humanitarian Nursing, 1941–51 400
The Healthy Socialist Life in Maoist China, 1949–1980 400
Walking a Tightrope: Memories of Wu Jieping, Personal Physician to China's Leaders 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3798859
求助须知:如何正确求助?哪些是违规求助? 3344607
关于积分的说明 10320917
捐赠科研通 3061108
什么是DOI,文献DOI怎么找? 1680042
邀请新用户注册赠送积分活动 806837
科研通“疑难数据库(出版商)”最低求助积分说明 763386