TY - JOUR
TI - Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma
AU - Mateos, M.-V.
AU - Dimopoulos, M.A.
AU - Cavo, M.
AU - Suzuki, K.
AU - Jakubowiak, A.
AU - Knop, S.
AU - Doyen, C.
AU - Lucio, P.
AU - Nagy, Z.
AU - Kaplan, P.
AU - Pour, L.
AU - Cook, M.
AU - Grosicki, S.
AU - Crepaldi, A.
AU - Liberati, A.M.
AU - Campbell, P.
AU - Shelekhova, T.
AU - Yoon, S.-S.
AU - Iosava, G.
AU - Fujisaki, T.
AU - Garg, M.
AU - Chiu, C.
AU - Wang, J.
AU - Carson, R.
AU - Crist, W.
AU - Deraedt, W.
AU - Nguyen, H.
AU - Qi, M.
AU - San-Miguel, J.
JO - The New England journal of medicine
PY - 2018
VL - 378
TODO - 6
SP - 518-528
PB - Massachussetts Medical Society
SN - null
TODO - 10.1056/NEJMoa1714678
TODO - 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
TODO - 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.
ER -