Year: 2017
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUNDThe 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. METHODSIn 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. RESULTSAt 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 10 5 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. CONCLUSIONSAmong 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.govnumber, NCT02195479.
Source: New England Journal of Medicine
Authors: María-Victoria Mateos, Meletios A. Dimopoulos, Michele Cavo, Kenshi Suzuki, Andrzej Jakubowiak, Stefan Knop, Chantal Doyen, Paulo Lucio, Zsolt Nagy, Polina Kaplan, Ludek Pour, Mark Cook, Sebastian Grosicki, Andre Crepaldi, Anna M. Liberati, Philip Campbell, Tatiana Shelekhova, Sung-Soo Yoon, Genadi Iosava, Tomoaki Fujisaki, Mamta Garg, Christopher Chiu, Jianping Wang, Robin Carson, Wendy Crist, William Deraedt, Huong Nguyen, Ming Qi, Jesus San-Miguel
Institutions: National and Kapodistrian University of Athens, Navarre Institute of Health Research, Instituto de Investigación Biomédica de Salamanca, Clinica Universidad de Navarra, University of Bologna, Japanese Red Cross Medical Center, University of Chicago Medical Center, Universitätsklinikum Würzburg, Semmelweis University, University Hospital Brno, University Hospitals Birmingham NHS Foundation Trust, Medical University of Silesia, Azienda Ospedaliera S.Maria, Geelong Hospital, Seoul National University, Matsuyama Red Cross Hospital, Leicester Royal Infirmary, Janssen Research & Development (United States), Janssen (Belgium), Centro de Investigación Biomédica en Red de Cáncer, Centro de Investigación Médica Aplicada
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Janssen Research and Development
OpenAlex ID: W2772566228