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N Engl J Med. 2019 May 30;380(22):2104-2115. doi: 10.1056/NEJMoa1817249.

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma.

Collaborators (184)

Baker R, Hocking J, Huey-Shin CL, Janowski W, Mollee P, Quach H, Ramanathan S, Renwick W, Wickham N, Fillitz M, Greil R, Gunsilius E, Krauth MT, Lechner D, Caers J, Delforge M, Kentos A, Bahlis N, Fox S, Gallagher G, Lemieux Blanchard E, Sebag M, Trudel S, Venner C, White D, Abildgaard N, Andersen NF, Plesner T, Allangba O, Araujo C, Arnulf B, Attal M, Belhadj-Merzoug K, Benboubker L, Benramdane R, Bouketouche M, Bourgeois E, Bouscary D, Caillot D, Chaleteix C, Choquet S, Decaux O, Demarquette H, Dib M, Eisenmann JC, Facon T, Fohrer-Sonntag C, Frenzel L, Garderet L, Godmer P, Guyotat D, Hulin C, Jaccard A, Karlin L, Kolb B, Leleu X, Lenain P, Macro M, Moreau P, Morel P, Orsini-Piocelle F, Pegourie B, Perrot A, Richez V, Rigaudeau S, Rodon P, Sanhes L, Stoppa AM, Thannberger A, Tiab M, Vincent L, Voog E, Zarnitsky C, Aulitzky W, Dürig J, Goldschmidt H, Hensel M, Junghanss C, Klausmann M, Krauter J, Mayr HC, Munder M, Röllig C, Rueckert A, Schub N, Thomalla J, von Metzler I, Wattad M, Weisel K, Coyne M, O'Dwyer M, Avivi I, Ben-Yehuda D, Preis M, Sofer O, Suriu C, Vaxman I, Bosi A, Caravita Di Toritto T, Giuliani N, Petrini M, Beeker A, Brada S, Broijl A, Blimark C, Flogegard M, Hansson M, Karlsson C, Lauri B, Nahi H, Basu S, Blundell J, Cavenagh J, Cavet J, Cook G, Hunter H, Jenner M, Lindsay J, Marron G, Rabin N, Ramasamy K, Rocci A, Tighe J, Williams C, Agajanian R, Alkaied H, Amjad M, Anz B 3rd, Armas A, Babu S, Berdeja J, Bhutani D, Brenner W, Chanan-Khan A, Chari A, Chaualgain C, Chaudhry A, Chen F, Cruz W, Drew D, Erikson B, Gabayan AE, Gabrail N, Galindo E, Goldstein M, Hansen V, Ifthikharuddin J, Janakiraman N, Karnat A, Kirkel D, Knapp M, Kocoglu M, Kumar S, Kuzma C, Lewis D, Libby E, Lunin S, Lunning M, Mace J, Malad S, McCaul K, Miller C, Moore M, Nooka A, Orlowski R, Parker T, Paroly W, Pati A, Peguero J, Raje N, Rosko A, Sadashiv S, Saez R, Saleh A, Schuster S, Singh J, Staszewski H, Stevens D, Stockerl-Goldstein K, Sumrall B, Usmani S, Valent J, Weng D, Yen C.

Author information

1
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.).

Abstract

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 105 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.).

PMID:
31141632
DOI:
10.1056/NEJMoa1817249
[Indexed for MEDLINE]

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