FDA Approves Daratumumab in Combination With VMP for Newly Diagnosed Patients With Multiple Myeloma Who Are Transplant-Ineligible

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 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 daratumumab in combination with VMP is supported by data from the randomized, open-label, multicenter phase III ALCYONE (MMY3007) study, recently published by Mateos et al in The New England Journal of Medicine. The combination of daratumumab 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 (PFS) for daratumumab plus VMP had not yet been reached, compared to a median PFS 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 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.”

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 three-fold increase in the minimal residual disease (MRD) negativity rate (22% vs 6%) compared to those who received VMP alone.

In the ALYCONE 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%). The warnings and precautions for daratumumab include infusion reactions, interference with cross-matching, and red blood cell antibody screening, neutropenia, and thrombocytopenia.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.




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