伊沙佐米、硼替佐米、来那度胺和地塞米松治疗多发性骨髓瘤。
Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma.
机构信息
From the Department of Hematology, Centre Hospitalier Universitaire (CHU) de Lille, University of Lille, Lille (T.F., S. Manier), the French National Academy of Medicine (T.F.), and the Department of Hematology, Hôpital Saint-Antoine, Sorbonne University and INSERM (M.M.), Paris, Service d'Hématologie et Thérapie Cellulaire, CHU and Centre d'Investigation Clinique INSERM Unité 1402, Poitiers (X.P.L.), the Department of Hematology, University Hospital Hôtel-Dieu, Nantes (P.M.), and Sanofi, Research and Development, Vitry-sur-Seine (C.O., M.-F.B., S. Macé, C.B.) - all in France; the Plasma Cell Dyscrasia Unit, Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens (M.-A.D.); the Department of Hematology, Ankara University, and the Istinye University Ankara Liv Hospital, Ankara (M.B.), and the Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul (S.K.-B.) - all in Turkey; the Department of Internal Medicine, Hematology, and Oncology, University Hospital Brno, Brno (L.P.), the Department of Hemato-Oncology, University Hospital Ostrava, and the Faculty of Medicine, University of Ostrava, Ostrava (R.H.), the Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University and University Hospital Olomouc, Olomouc (J.M.), and the Charles University and General Hospital in Prague, Prague (I.S.) - all in the Czech Republic; Shengjing Hospital of China Medical University, Shenyang, China (Z.L.); the Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw (J.R.-J.), and the Department of General Hematology, Copernicus Memorial Hospital, Comprehensive Cancer Center and Traumatology, Łódź (P.R.) - both in Poland; the S.P. Botkin Moscow City Clinical Hospital, Moscow (V.I.V.); the Department of Hematology, Oncology, Immunology, and Rheumatology, University Hospital of Tübingen, Tübingen (B.B.), and the Department of Internal Medicine V, University of Heidelberg, Heidelberg (H.G.) - both in Germany; the Japanese Red Cross Medical Center, Tokyo (T.I.); Calvary Mater Newcastle, Newcastle, NSW (W.J.), and the Illawarra Cancer Care Centre, Wollongong, NSW (G.P.) - both in Australia; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli," and Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy (E.Z.); the Division of Hematology-Oncology, University of California, San Francisco, San Francisco (T.G.M.); Sanofi, Patient Safety and Pharmacovigilance, Bridgewater, NJ (D.B.); Sanofi, Cambridge, MA (Z.K.); and the Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston (R.Z.O.).
出版信息
N Engl J Med. 2024 Oct 31;391(17):1597-1609. doi: 10.1056/NEJMoa2400712. Epub 2024 Jun 3.
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.).
背景
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。对于不适合进行移植的患者，在 VRd 方案中添加抗 CD38 单克隆抗体伊沙妥昔单抗是否会降低疾病进展或死亡的风险尚不清楚。
方法
在一项国际性、开放性、3 期临床试验中，我们以 3:2 的比例随机分配 18 至 80 岁的新诊断多发性骨髓瘤且不适合进行移植的患者，分别接受伊沙妥昔单抗联合 VRd 或 VRd 单独治疗。主要疗效终点为无进展生存期。关键次要终点包括完全缓解或更好和完全缓解患者的微小残留病（MRD）阴性状态。
结果
共有 446 名患者接受了随机分组。在中位随访 59.7 个月时，伊沙妥昔单抗-VRd 组的 60 个月无进展生存率估计为 63.2%，而 VRd 组为 45.2%（疾病进展或死亡的风险比，0.60；98.5%置信区间，0.41 至 0.88；P<0.001）。伊沙妥昔单抗-VRd 组完全缓解或更好的患者比例明显高于 VRd 组（74.7%比 64.1%，P=0.01），MRD 阴性且完全缓解的患者比例也明显高于 VRd 组（55.5%比 40.9%，P=0.003）。伊沙妥昔单抗-VRd 方案未观察到新的安全性信号。两组治疗期间严重不良事件的发生率和导致停药的不良事件的发生率相似。
结论
对于不适合进行移植的新诊断多发性骨髓瘤且年龄在 18 至 80 岁的患者，伊沙妥昔单抗-VRd 作为初始治疗比 VRd 更有效。（由 Sanofi 和癌症中心支持赠款资助；IMROZ ClinicalTrials.gov 编号，NCT03319667.）。
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