Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.

IF 96.2 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL New England Journal of Medicine Pub Date : 2024-10-31 Epub Date: 2024-06-03 DOI:10.1056/NEJMoa2400712
Thierry Facon, Meletios-Athanasios Dimopoulos, Xavier P Leleu, Meral Beksac, Ludek Pour, Roman Hájek, Zhuogang Liu, Jiri Minarik, Philippe Moreau, Joanna Romejko-Jarosinska, Ivan Spicka, Vladimir I Vorobyev, Britta Besemer, Tadao Ishida, Wojciech Janowski, Sevgi Kalayoglu-Besisik, Gurdeep Parmar, Pawel Robak, Elena Zamagni, Hartmut Goldschmidt, Thomas G Martin, Salomon Manier, Mohamad Mohty, Corina Oprea, Marie-France Brégeault, Sandrine Macé, Christelle Berthou, David Bregman, Zandra Klippel, Robert Z Orlowski
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引用次数: 0

Abstract

Background: Bortezomib, lenalidomide, and dexamethasone (VRd) is a preferred first-line treatment option for patients with newly diagnosed multiple myeloma. Whether the addition of the anti-CD38 monoclonal antibody isatuximab to the VRd regimen would reduce the risk of disease progression or death among patients ineligible to undergo transplantation is unclear.

Methods: In an international, open-label, phase 3 trial, we randomly assigned, in a 3:2 ratio, patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation to receive either isatuximab plus VRd or VRd alone. The primary efficacy end point was progression-free survival. Key secondary end points included a complete response or better and minimal residual disease (MRD)-negative status in patients with a complete response.

Results: A total of 446 patients underwent randomization. At a median follow-up of 59.7 months, the estimated progression-free survival at 60 months was 63.2% in the isatuximab-VRd group, as compared with 45.2% in the VRd group (hazard ratio for disease progression or death, 0.60; 98.5% confidence interval, 0.41 to 0.88; P<0.001). The percentage of patients with a complete response or better was significantly higher in the isatuximab-VRd group than in the VRd group (74.7% vs. 64.1%, P = 0.01), as was the percentage of patients with MRD-negative status and a complete response (55.5% vs. 40.9%, P = 0.003). No new safety signals were observed with the isatuximab-VRd regimen. The incidence of serious adverse events during treatment and the incidence of adverse events leading to discontinuation were similar in the two groups.

Conclusions: Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation. (Funded by Sanofi and a Cancer Center Support Grant; IMROZ ClinicalTrials.gov number, NCT03319667.).

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伊沙妥昔单抗、硼替佐米、来那度胺和地塞米松治疗多发性骨髓瘤。
背景:硼替佐米、来那度胺和地塞米松(VRd硼替佐米、来那度胺和地塞米松(VRd)是新诊断多发性骨髓瘤患者的首选一线治疗方案。在VRd方案中加入抗CD38单克隆抗体伊沙妥昔单抗是否会降低不符合移植条件的患者的疾病进展或死亡风险,目前尚不清楚:在一项国际开放标签三期试验中,我们以3:2的比例随机分配了18至80岁、新诊断为多发性骨髓瘤且不符合移植条件的患者,让他们接受伊沙妥昔单抗联合VRd或单用VRd。主要疗效终点是无进展生存期。主要次要终点包括完全应答或更好,以及完全应答患者的最小残留病(MRD)阴性状态:共有 446 名患者接受了随机化治疗。在中位随访59.7个月时,伊沙妥昔单抗-VRd组患者60个月时的无进展生存率估计为63.2%,而VRd组为45.2%(疾病进展或死亡的危险比为0.60;98.5%置信区间为0.41至0.88;PC结论:伊沙妥昔单抗-VRd组患者60个月时的无进展生存率估计为63.2%,而VRd组为45.2%:对于不符合移植条件的18至80岁新诊断多发性骨髓瘤患者,伊沙妥昔单抗-VRd作为初始疗法比VRd更有效。(由赛诺菲和癌症中心支持基金资助;IMROZ ClinicalTrials.gov 编号:NCT03319667)。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
New England Journal of Medicine
New England Journal of Medicine 医学-医学:内科
CiteScore
145.40
自引率
0.60%
发文量
1839
审稿时长
1 months
期刊介绍: The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.
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