BACKGROUND: Daratumumab, a human IgGκ monoclonal antibody that targets CD38, 
induces direct and indirect antimyeloma activity and has shown substantial 
efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as 
well as in combination with bortezomib in patients with newly diagnosed multiple 
myeloma.
METHODS: In this phase 3 trial, we randomly assigned 498 patients with relapsed 
or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per 
square meter of body-surface area) and dexamethasone (20 mg) alone (control 
group) or in combination with daratumumab (16 mg per kilogram of body weight) 
(daratumumab group). The primary end point was progression-free survival.
RESULTS: A prespecified interim analysis showed that the rate of 
progression-free survival was significantly higher in the daratumumab group than 
in the control group; the 12-month rate of progression-free survival was 60.7% 
in the daratumumab group versus 26.9% in the control group. After a median 
follow-up period of 7.4 months, the median progression-free survival was not 
reached in the daratumumab group and was 7.2 months in the control group (hazard 
ratio for progression or death with daratumumab vs. control, 0.39; 95% 
confidence interval, 0.28 to 0.53; P<0.001). The rate of overall response was 
higher in the daratumumab group than in the control group (82.9% vs. 63.2%, 
P<0.001), as were the rates of very good partial response or better (59.2% vs. 
29.1%, P<0.001) and complete response or better (19.2% vs. 9.0%, P=0.001). Three 
of the most common grade 3 or 4 adverse events reported in the daratumumab group 
and the control group were thrombocytopenia (45.3% and 32.9%, respectively), 
anemia (14.4% and 16.0%, respectively), and neutropenia (12.8% and 4.2%, 
respectively). Infusion-related reactions that were associated with daratumumab 
treatment were reported in 45.3% of the patients in the daratumumab group; these 
reactions were mostly grade 1 or 2 (grade 3 in 8.6% of the patients), and in 
98.2% of these patients, they occurred during the first infusion.
CONCLUSIONS: Among patients with relapsed or relapsed and refractory multiple 
myeloma, daratumumab in combination with bortezomib and dexamethasone resulted 
in significantly longer progression-free survival than bortezomib and 
dexamethasone alone and was associated with infusion-related reactions and 
higher rates of thrombocytopenia and neutropenia than bortezomib and 
dexamethasone alone. (Funded by Janssen Research and Development; 
ClinicalTrials.gov number, NCT02136134.).