From University of Lille, Centre Hospitalier Universitaire (CHU) Lille, Service des Maladies du Sang, Lille (T.F.), Hematology Department, University Hospital Hôtel-Dieu, Nantes (P.M.), Department of Hematology, Hospital Haut Leveque, University Hospital, Pessac (C.H.), Hematology Department, University Hospital, Vandoeuvre lès Nancy (A.P.), Service d'Hématologie, CHU de Toulouse-Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (M.A.), Department of Hematology, Vendée Hospital, La Roche sur Yon (M.T.), CHU de Caen, Caen (M.M.), Department of Clinical Hematology, Assistance Publique-Hôpitaux de Paris, Necker Hospital, Paris (L.F.), and Department of Hematology, CHU la Miletrie and INSERM CIC 1402, Poitiers (X.L.) - all in France; the Department of Hematology, Mayo Clinic Rochester, Rochester, MN (S.K.); Vejle Hospital and University of Southern Denmark, Vejle (T.P.); Department of Lymphoma-Myeloma, University of Texas M.D. Anderson Cancer Center, Houston (R.Z.O.); University of Calgary, Arnie Charbonneau Cancer Research Institute, Calgary, AB (N.B.), and the Division of Medical Oncology, University of Alberta, Edmonton (C.P.V.) - both in Canada; Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom (S.B.); Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm (H.N.); University of Melbourne, St. Vincent's Hospital, Melbourne, VIC, Australia (H.Q.); University Hospital Heidelberg and National Center of Tumor Diseases (NCT), Heidelberg (H.G.), and the Department of Oncology, Hematology and Bone Marrow Transplantation, Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg (K.W.) - both in Germany; Department of Medicine-Haematology, National University of Ireland, Galway (M.O.); Florida Cancer Specialists and Research Institute, St. Petersburg (J.R.M.); the Department of Hematology-Oncology, Massachusetts General Hospital, Boston (N.R.); Genmab US, Princeton (T.A.), and Janssen Research and Development, Raritan (J.W., R.K.) - both in New Jersey; Janssen Research and Development, Spring House, PA (C.C., C.M.U., M.Q.); Janssen Research and Development, Beerse, Belgium (R.V.R.); and Levine Cancer Institute-Atrium Health, Charlotte, NC (S.Z.U.).
N Engl J Med. 2019 May 30;380(22):2104-2115. doi: 10.1056/NEJMoa1817249.
BACKGROUND: Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population. METHODS: We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival. RESULTS: At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 10 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%). CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone. A higher incidence of neutropenia and pneumonia was observed in the daratumumab group. (Funded by Janssen Research and Development; MAIA ClinicalTrials.gov number, NCT02252172.).
背景：来那度胺联合地塞米松是不适合自体干细胞移植的新发多发性骨髓瘤患者的标准治疗方法。我们旨在确定达雷妥尤单抗的加入是否会显著降低该人群的疾病进展或死亡风险。
方法：我们随机分配了 737 名不适合自体干细胞移植的新发多发性骨髓瘤患者，接受达雷妥尤单抗联合来那度胺和地塞米松（达雷妥尤单抗组）或来那度胺和地塞米松单药治疗（对照组）。治疗将持续至疾病进展或出现不可接受的副作用。主要终点是无进展生存期。
结果：在中位随访 28.0 个月时，240 名患者（达雷妥尤单抗组 368 名患者中的 97 名[26.4%]和对照组 369 名患者中的 143 名[38.8%]）发生疾病进展或死亡。30 个月时无疾病进展生存的患者估计百分比为达雷妥尤单抗组 70.6%（95%置信区间[CI]，65.0 至 75.4），对照组为 55.6%（95% CI，49.5 至 61.3）（疾病进展或死亡的风险比，0.56；95%CI，0.43 至 0.73；P<0.001）。达雷妥尤单抗组完全缓解或更好的患者比例为 47.6%，对照组为 24.9%（P<0.001）。达雷妥尤单抗组有 24.2%的患者，而对照组有 7.3%的患者，其微小残留疾病（每 10 个白细胞中有 1 个肿瘤细胞）检测结果低于阈值（P<0.001）。3 级或 4 级最常见的不良事件为中性粒细胞减少症（达雷妥尤单抗组 50.0%，对照组 35.3%）、贫血（11.8% vs. 19.7%）、淋巴细胞减少症（15.1% vs. 10.7%）和肺炎（13.7% vs. 7.9%）。
结论：在不适合自体干细胞移植的新发多发性骨髓瘤患者中，与接受来那度胺和地塞米松单药治疗的患者相比，接受达雷妥尤单抗联合来那度胺和地塞米松治疗的患者疾病进展或死亡的风险显著降低。达雷妥尤单抗组观察到中性粒细胞减少症和肺炎的发生率更高。（由 Janssen Research and Development 资助；MAIA 临床试验.gov 编号，NCT02252172。）
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