The FDA has approved daratumumab in combination with bortezomib, melphalan, and prednisone to treat patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.
Patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant now have a new first-line treatment available to them. The FDA has approved daratumumab (sold as Darzalex by Johnson & Johnson) in combination with the proteasome inhibitor bortezomib (Velcade), alkylating agent melphalan, and prednisone (VMP).
The approval of daratumumab was based on findings from phase 3 of the ALCYONE study, a randomized, open-label, multicenter study with results published February 8, 2018, in New England Journal of Medicine.
“This approval is significant as we now have the first antibody-based regimen for treating newly diagnosed multiple myeloma patients who are not eligible for a stem cell transplant,” Andrzej Jakubowiak, MD, PhD, director of the Multiple Myeloma Program at University of Chicago Medical Center and a Darzalex clinical study investigator, said in a statement. “In clinical studies, patients who received treatment with daratumumab experienced a lower risk of disease progression and higher rates of response.”
In the study, 706 patients were randomly assigned to the control group (bortezomib, melphalan, and prednisone) or the daratumumab group (bortezomib, melphalan, and prednisone, plus daratumumab). The study found that the 18-month progression-free survival rate was 71.6% among patients who took daratumumab, compared with 50.2% among patients in the control group, who received bortezomib, melphalan, and prednisone alone.
The study also found a better overall response rate (90.9% with daratumumab vs 73.9% in the control group) and a better rate of complete response (42.6% vs 24.4%). Rates of grade 3 or 4 infections were higher in the daratumumab group (23.1%) compared with the control group (14.7%), but the rate of treatment discontinuation due to infection was lower (0.9% in daratumumab group vs 1.4% in control group).
The most common grade 3 or 4 adverse events were neutropenia (39.9% in daratumumab group and 38.7% in control group), thrombocytopenia (34.4% and 37.6%), and anemia (15.9% and 19.8%).
"A patient's best chance at lasting remission often begins with a durable response to frontline therapy, because multiple myeloma can become more difficult to treat after relapse," said Maria-Victoria Mateos, MD, PhD, director of the Myeloma Unit at University Hospital of Salamanca-IBSAL and ALCYONE primary investigator. "Combination therapy with daratumumab resulted in deep and durable responses in newly diagnosed patients with multiple myeloma who are transplant ineligible, supporting this regimen as an important new treatment option for these patients."
This is the fifth indication for daratumumab, which was first approved in November 2015 as a monotherapy for patients with multiple myeloma who have received at least 3 previous lines of therapy.
Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518-528. doi: 10.1056/NEJMoa1714678.