@article{3107692, title = "Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma", author = "Mateos, M.-V. and Dimopoulos, M.A. and Cavo, M. and Suzuki, K. and Jakubowiak, A. and Knop, S. and Doyen, C. and Lucio, P. and Nagy, Z. and Kaplan, P. and Pour, L. and Cook, M. and Grosicki, S. and Crepaldi, A. and Liberati, A.M. and Campbell, P. and Shelekhova, T. and Yoon, S.-S. and Iosava, G. and Fujisaki, T. and Garg, M. and Chiu, C. and Wang, J. and Carson, R. and Crist, W. and Deraedt, W. and Nguyen, H. and Qi, M. and San-Miguel, J.", journal = "The New England journal of medicine", year = "2018", volume = "378", number = "6", pages = "518-528", publisher = "Massachussetts Medical Society", doi = "10.1056/NEJMoa1714678", keywords = "bortezomib; daratumumab; melphalan; prednisone; antineoplastic agent; bortezomib; daratumumab; melphalan; monoclonal antibody; prednisone, adult; aged; Article; cancer survival; controlled study; disease severity; drug efficacy; drug safety; drug tolerability; female; follow up; human; major clinical study; multiple cycle treatment; multiple myeloma; neutropenia; outcome assessment; phase 3 clinical trial; priority journal; progression free survival; randomized controlled trial; stem cell transplantation; survival rate; thrombocytopenia; tumor cell; chemically induced; clinical trial; disease free survival; infection; intention to treat analysis; Kaplan Meier method; male; middle aged; mortality; multicenter study; multiple myeloma, Adult; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Disease-Free Survival; Female; Follow-Up Studies; Humans; Infection; Intention to Treat Analysis; Kaplan-Meier Estimate; Male; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Survival Rate", abstract = "BACKGROUND: The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 706 patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation to receive nine cycles of bortezomib, melphalan, and prednisone either alone (control group) or with daratumumab (daratumumab group) until disease progression. The primary end point was progression-free survival. RESULTS: At a median follow-up of 16.5 months in a prespecified interim analysis, the 18-month progression-free survival rate was 71.6% (95% confidence interval [CI], 65.5 to 76.8) in the daratumumab group and 50.2% (95% CI, 43.2 to 56.7) in the control group (hazard ratio for disease progression or death, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The overall response rate was 90.9% in the daratumumab group, as compared with 73.9% in the control group (P<0.001), and the rate of complete response or better (including stringent complete response) was 42.6%, versus 24.4% (P<0.001). In the daratumumab group, 22.3% of the patients were negative for minimal residual disease (at a threshold of 1 tumor cell per 105 white cells), as compared with 6.2% of those in the control group (P<0.001). The most common adverse events of grade 3 or 4 were hematologic: neutropenia (in 39.9% of the patients in the daratumumab group and in 38.7% of those in the control group), thrombocytopenia (in 34.4% and 37.6%, respectively), and anemia (in 15.9% and 19.8%, respectively). The rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group; the rate of treatment discontinuation due to infections was 0.9% and 1.4%, respectively. Daratumumabassociated infusion-related reactions occurred in 27.7% of the patients. CONCLUSIONS: Among patients with newly diagnosed multiple myeloma who were ineligible for stemcell transplantation, daratumumab combined with bortezomib, melphalan, and prednisone resulted in a lower risk of disease progression or death than the same regimen without daratumumab. The daratumumab-containing regimen was associated with more grade 3 or 4 infections. (Funded by Janssen Research and Development; ALCYONE ClinicalTrials.gov number, NCT02195479). Copyright © 2017 Massachusetts Medical Society." }