FDA Approves Darzalex Combination for Newly Diagnosed Multiple Myeloma

The Food and Drug Administration (FDA) granted approval to Darzalex (daratumumab) in combination with Velcade (bortezomib), melphalan and prednisone — also known as VMP – for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).

With this approval, Darzalex (manufactured by Janssen) is the first monoclonal antibody approved for newly diagnosed patients — also marking the agent’s fifth indication for multiple myeloma.

"Slowing the progression of myeloma translates to more time in remission for those battling the disease. This latest approval for Darzalex in combination with VMP is an exciting step forward for newly diagnosed patients and the health care teams who treat them," Paul Giusti, President and CEO of the Multiple Myeloma Research Foundation (MMRF), said in a press release. "The MMRF congratulates Janssen, our long-time collaborator in myeloma research, the dedicated health care providers in the myeloma community as well as the patients who donate their time and data on clinical trials, for making this critical new combination therapy possible."

Darzalex study investigator Andrzej Jakubowiak, M.D., Ph.D., who is also Director of the Multiple Myeloma Program at University of Chicago Medical Center, agreed with the significance of the FDA’s decision. "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," he said. "In clinical studies, patients who received treatment with daratumumab experienced a lower risk of disease progression and higher rates of response."

The agency’s decision included results from the randomized, open-label, multicenter phase 3 ALCYONE study, designed to compare Darzalex in combination with VMP (350 patients) versus VMP alone (356 patients) in patients with newly diagnosed multiple myeloma.

VMP was administered at standard doses and daratumumab was added at 16 mg/kg once weekly in cycle 1 and every 3 weeks in cycles 2 through 9. Beyond month 9 in the investigational arm, daratumumab was continued every 4 weeks until disease progression.

The combination reduced the risk of disease progression or death by 50 percent compared to treatment with VMP alone. However, median progression-free survival (PFS) for the combination regimen had not yet been reached, compared to a median PFS of 18.1 months for patients who received VMP alone.

The Darzalex combination also showed improved overall response rates (ORR; 91 percent vs. 74 percent), which included more stringent complete responses (18 percent vs. 7 percent) and complete responses or better (43 percent vs. 24 percent) and very good partial responses or better (71 percent vs. 50 percent), compared with VMP alone.

Patients in the Darzalex arm also experienced a three-fold increase in the minimal residual disease (MRD) negativity rate (22 percent vs. 6 percent).

"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 primary investigator Maria-Victoria Mateos, M.D., Ph.D., Director of the Myeloma Unit at University Hospital of Salamanca-IBSAL in Spain. "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."

The most common side effects included upper respiratory tract infection (48 percent vs. 28 percent), infusion reactions (28 percent vs. 0 percent) and peripheral edema (21 percent vs. 14 percent) in the combination arm compared with VMP alone. Serious side effects included pneumonia (11 percent vs. 4 percent), upper respiratory tract infection (5 percent vs. 1 percent) and pulmonary edema (2 percent vs. 0 percent), respectively.