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.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.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. Daratumumab-associated infusion-related
reactions occurred in 27.7% of the patients.Among patients with newly diagnosed multiple
myeloma who were ineligible for stem-cell 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 .).
