@article{ffd944cd380c451b9c5a0973e59aae0c,
title = "Daratumumab plus lenalidomide and dexamethasone for untreated Myeloma",
abstract = "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%).",
author = "T. Facon and S. Kumar and T. Plesner and Orlowski, {R. Z.} and P. Moreau and N. Bahlis and S. Basu and H. Nahi and C. Hulin and H. Quach and H. Goldschmidt and M. O{\textquoteright}Dwyer and A. Perrot and Venner, {C. P.} and K. Weisel and Mace, {J. R.} and N. Raje and M. Attal and M. Tiab and M. Macro and L. Frenzel and X. Leleu and T. Ahmadi and C. Chiu and J. Wang and Rampelbergh, {R. Van} and Uhlar, {C. M.} and R. Kobos and M. Qi and Usmani, {S. Z.}",
note = "Funding Information: A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Supported by Janssen Research and Development. Funding Information: Dr. Facon reports receiving fees for serving on a board of directors, advisory committee, and speakers bureau from Celgene, Janssen, and Takeda, and fees for serving on a board of directors and advisory committee from Amgen, Sanofi, Karyopharm, Oncopeptides, and Roche; Dr. Kumar, receiving grant support and fees for serving on a board of directors and advisory committee from AbbVie, Celgene, and Kite Pharma; Dr. Plesner, serving on an independent response assessment committee for Celgene; Dr. Orlowski, receiving consulting fees and fees for serving on a board of directors and advisory committee from Bristol-Myers Squibb, Celgene, Kite Pharma, Sanofi, and Amgen, consulting fees from Takeda, and grant support from BioTheryX and Spectrum Pharma; Dr. Moreau, receiving honoraria and fees for serving on a board of directors, advisory committee, and speakers bureau from Amgen, Celgene, Janssen, AbbVie, and Takeda; Dr. Bahlis, receiving grant support, consulting fees, and honoraria from Amgen and Celgene; Dr. Hulin, receiving grant support and honoraria from Celgene and Janssen, and honoraria from Amgen and Takeda; Dr. Goldschmidt, receiving consulting fees and fees for serving on a board of directors and advisory committee from Adaptive Biotechnologies, grant support, consulting fees, and fees for serving on a board of directors and advisory committee from Amgen, Sanofi, and Takeda, grant support, consulting fees, honoraria, and fees for serving on a board of directors and advisory committee from Bristol-Myers Squibb, Celgene, and Janssen, honoraria and research funding from Chugai, grant support from Mundipharma, grant support and honoraria from Novartis, and honoraria from Art Tempi; Dr. O{\textquoteright}Dwyer, receiving consulting fees from Janssen; Dr. Perrot, receiving consulting fees, honoraria, and equity from Janssen; Dr. Venner, receiving grant support and honoraria from Janssen and Celgene, and honoraria from Amgen and Takeda; Dr. Weisel, receiving grant support, consulting fees, and honoraria from Janssen, consulting fees from Celgene and Juno, consulting fees, honoraria, and research funding from Amgen, consulting and honoraria from Bristol-Myers Squibb and Takeda, and grant support and consulting fees from Sanofi; Dr. Raje, receiving consulting fees from Amgen, Celgene, Bristol-Myers Squibb, Janssen, and Takeda, and grant support from Astra-Zeneca; Dr. Macro, receiving honoraria and travel support from Celgene and Amgen, and grant support, honoraria, and travel support from Janssen and Takeda; Dr. Leleu, receiving honoraria from Amgen, Takeda, Janssen, Bristol-Myers Squibb, Novartis, Roche, Merck, Mundipharma, Gilead, AbbVie, Karyopharm, Celgene, and Incyte; Dr. Ahmadi, being employed by and owning equity in Genmab; Dr. Chiu, being employed by and owning equity in Janssen; Dr. Wang, Dr. van Rampelbergh, Dr. Uhlar, Dr. Kobos, and Dr. Qi, being employed by Janssen; and Dr. Usmani, receiving consulting fees from AbbVie, Genmab, and Mundi-pharma, grant support and consulting fees from Amgen, Cel- gene, Merck, Janssen, and Seattle Genetics, and grant support from Bristol-Myers Squibb, Pharmacyclics, and Sanofi. No other potential conflict of interest relevant to this article was reported.",
year = "2019",
month = may,
day = "30",
doi = "10.1056/NEJMoa1817249",
language = "English (US)",
volume = "380",
pages = "2104--2115",
journal = "New England Journal of Medicine",
issn = "1533-4406",
publisher = "Massachussetts Medical Society",
number = "22",
}