Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study

泊马度胺 地塞米松 医学 多发性骨髓瘤 来那度胺 内科学 肿瘤科 耐火材料(行星科学) 生物 天体生物学
作者
Michel Attal,Paul G. Richardson,S. Vincent Rajkumar,Jesús F. San Miguel,Meral Beksaç,Ivan Špıčka,Xavier Leleu,Fredrik Schjesvold,Philippe Moreau,Meletios Α. Dimopoulos,Jeffrey Shang-Yi Huang,Jiri Minařík,Michèle Cavo,H. Miles Prince,Sandrine Macé,Kathryn P. Corzo,Frank Campana,Solenn Le-Guennec,Franck Dubin,Kenneth C. Anderson,Michel Attal,Paul G. Richardson,S. Vincent Rajkumar,Jesús F. San Miguel,Meral Beksaç,Ivan Špıčka,Xavier Leleu,Fredrik Schjesvold,Philippe Moreau,Meletios Α. Dimopoulos,Jeffrey Shang-Yi Huang,Jiri Minařík,Michèle Cavo,H. Miles Prince,Sandrine Macé,Kathryn P. Corzo,Frank Campana,Solenn Le-Guennec,Franck Dubin,Kenneth C. Anderson,Simon J. Harrison,Wojt Janowski,Ian Kerridge,Andrew Spencer,Michel Delforge,Karel Fostier,Philip Vlummens,Ka Lung Wu,Richard LeBlanc,Michel Pavic,Michaël Sébag,Roman Hájek,Vladimír Maisnar,Luděk Pour,Henrik Gregersen,Lotfi Benbouker,Denis Caillot,Martine Escoffre‐Barbe,Thierry Façon,Laurent Frenzel,Cyrille Hulin,Lionel Karlin,Brigitte Kolb,Brigitte Pegourié,Aurore Perrot,Jill Corre,Laure Vincent,Dietger Niederwieser,Αchilles Anagnostopoulos,Sosana Delimpasi,Marie‐Christine Kyrtsonis,Argiris Symeonidis,Árpád Illés,Gábor Mikala,Zsolt Nagy,Sara Bringen,Paolo Corradini,Fabio Ciceri,Roberto M. Lemoli,Anna Marina Liberati,Chiara Nozzoli,Renato Zambello,Shinsuke Iida,Takashi Ikeda,Satoshi Iyama,Morio Matsumoto,Chihiro Shimazaki,Kazutaka Sunami,Kenshi Suzuki,Michihiro Uchiyama,Youngil Koh,Kihyun Kım,Jae Hoon Lee,Chang‐Ki Min,Hillary Blacklock,Hugh J. B. Goodman,Annette Neylon,David Simpson,Sebastian Grosicki,Artur Jurczyszyn,Adam Walter‐Croneck,Krzysztof Warzocha,Luiz Felipe Lopez Araujo,Cláudia Moreira,Vadim Doronin,Л. П. Менделеева,Vladimir I. Vorobyev,Andrej Vranovský,Adrián Alegre,Mercedes Gironella,Marta Sonia González,Jaime Sanz,Enrique M. Ocio,Paula Rodríguez,Mats Hardling,Birgitta Lauri,Ming-Chung Wang,Su‐Peng Yeh,Mutlu Arat,Fatih Demırkan,Zafer Gülbaş,Sevgi Kalayoğlu Beşışık,Ìhsan Karadoǧan,Tülin Tuğlular,Ali Ünal,Filiz Vural,Jonathan Sive,Matthew Streetly,Kwee Yong,Jason Tache
出处
期刊:The Lancet [Elsevier]
卷期号:394 (10214): 2096-2107 被引量:504
标识
DOI:10.1016/s0140-6736(19)32556-5
摘要

Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma.We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (<75 years vs ≥75 years). Treatments were assigned based on a permuted blocked randomisation scheme with a block size of four. The isatuximab-pomalidomide-dexamethasone group received isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, number NCT02990338.Between Jan 10, 2017, and Feb 2, 2018, we randomly assigned 307 patients to treatment: 154 to isatuximab-pomalidomide-dexamethasone, and 153 to pomalidomide-dexamethasone. At a median follow-up of 11·6 months (IQR 10·1-13·9), median progression-free survival was 11·5 months (95% CI 8·9-13·9) in the isatuximab-pomalidomide-dexamethasone group versus 6·5 months (4·5-8·3) in the pomalidomide-dexamethasone group; hazard ratio 0·596, 95% CI 0·44-0·81; p=0·001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab-pomalidomide-dexamethasone vs pomalidomide-dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab-pomalidomide-dexamethasone group and 14 (9%) in the pomalidomide-dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (<1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection).The addition of isatuximab to pomalidomide-dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor.Sanofi. VIDEO ABSTRACT.
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
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
氙气飘飘发布了新的文献求助10
刚刚
雷小牛发布了新的文献求助10
1秒前
小胡发布了新的文献求助10
1秒前
2秒前
2秒前
Kyrc完成签到 ,获得积分10
2秒前
zhao发布了新的文献求助200
2秒前
南木_完成签到,获得积分10
3秒前
4秒前
大个应助wonder采纳,获得10
4秒前
11111完成签到,获得积分10
4秒前
马金华完成签到,获得积分10
4秒前
璐璐发布了新的文献求助10
4秒前
4秒前
摔碎玻璃瓶完成签到,获得积分10
5秒前
5秒前
王翼发布了新的文献求助20
5秒前
6秒前
未末木发布了新的文献求助10
7秒前
7秒前
7秒前
Sabrina发布了新的文献求助30
7秒前
一只小可爱完成签到,获得积分10
7秒前
抹茶肥肠发布了新的文献求助10
7秒前
8秒前
鱼前发布了新的文献求助10
8秒前
静静发布了新的文献求助10
9秒前
所所应助雷雨田采纳,获得30
9秒前
开放的白玉完成签到,获得积分10
9秒前
花儿发布了新的文献求助10
9秒前
10秒前
李红跃发布了新的文献求助10
10秒前
王毅发布了新的文献求助10
11秒前
Bunny发布了新的文献求助10
11秒前
11秒前
NexusExplorer应助如意的山水采纳,获得10
12秒前
星辰大海应助TEN110684采纳,获得10
12秒前
翁沛山完成签到 ,获得积分10
14秒前
Lucas应助浅笑暖暖采纳,获得10
14秒前
123完成签到,获得积分10
15秒前
高分求助中
좌파는 어떻게 좌파가 됐나:한국 급진노동운동의 형성과 궤적 2500
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
CLSI EP47 Evaluation of Reagent Carryover Effects on Test Results, 1st Edition 800
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
Retention of title in secured transactions law from a creditor's perspective: A comparative analysis of selected (non-)functional approaches 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3054835
求助须知:如何正确求助?哪些是违规求助? 2711704
关于积分的说明 7427777
捐赠科研通 2356290
什么是DOI,文献DOI怎么找? 1248044
科研通“疑难数据库(出版商)”最低求助积分说明 606566
版权声明 596083