On May 7, the U.S. Food and Drug Administration(FDA) approved daratumumab (Darzalex) in combination with bortezomib (Velcade), a proteasome inhibitor; melphalan, an alkylating agent; and prednisone—VMP—for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). Daratumumab is the first monoclonal antibody approved for newly diagnosed patients with this disease. Clinical trial results showed daratumumab in combination with VMP reduced the risk of disease progression or death by 50% compared to treatment with VMP alone.
“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,” said Andrzej Jakubowiak, MD, PhD, Director of the Multiple Myeloma Program at the University of Chicago Medical Center, and a daratumumab clinical study investigator. “In clinical studies, patients who received treatment with daratumumab experienced a lower risk of disease progression and higher rates of response.”
The FDA approval of daratumu-mab in combination with VMP is supported by data from the randomized, open--label, multicenterphase III ALCYONE (MMY3007) study, recently published by Mateos et al.1 The combination of daratumu-mab with VMP reduced the risk of disease progression or death by 50%, compared to treatment with VMP alone (hazard ratio [HR] = 0.50; 95% confidence interval [CI] = 0.38–0.65, P < .0001). The median progression-free survival for daratumumab plus VMP had not yet been reached, compared to a median progression-free survival of 18.1 months for patients who received VMP alone.
“A patient’s best chance at lasting remission often begins with a durable response to front-line therapy, because multiple myeloma can become more difficult to treat after relapse,” said Maria-Victoria Mateos, MD, PhD, Director of the Myeloma Unit at the University Hospital of Salamanca-IBSALand 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.”
Combination Therapy Yielded-Improved Response
Treatment with daratumumab in combination with VMP significantly improved overall response rates (91% vs 74%) compared to VMP alone. Additionally, measures of stringent complete response (18% vs 7%), complete response or better (43% vs 24%), and very good partial response or better (71% vs 50%) all showed marked improvement. Patients receiving daratumumab in combination with VMP achieved a more than threefold increase in the minimal residual disease negativity rate (22% vs 6%) compared to those who received VMP alone.
In the ALCYONE study, the most frequent adverse reactions (> 20%) with at least 5% greater frequency in the daratumumab/VMP arm were upper respiratory tract infection (48% vs 28%), infusion reactions (28% vs 0%), and peripheral edema (21% vs 14%). Serious adverse reactions with at least a 2% greater incidence in the daratumumab/VMP arm vs VMP were pneumonia (11% vs 4%), upper respiratory tract infection (5% vs 1%), and pulmonary edema (2% vs 0%). The most common grade 3/4 treatment-emergent hematology laboratory abnormalities for daratumumab/VMP vs VMP were lymphopenia (58% vs 53%), neutropenia (44% vs 43%), and thrombocytopenia (38% vs 42%). Warnings and precautions for daratumu-mab include infusion reactions, and interference with cross-matching and red blood cell antibody screening. ■
1. Mateos MV, Dimopoulos MA, Cavo M, et al: Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med 378:518-528, 2018.