FDA Approves Darzalex Combo for Newly Diagnosed Multiple Myeloma Patients Eligible for Transplant

The U.S. Food and Drug Administration (FDA) has approved Darzalex (daratumumab), in combination with Velcade (bortezomib), thalidomide and dexamethasone (collectively known as VTd), to treat newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant (ASCT).

Darzalex is an antibody designed to recognize and block the activity of CD38, a protein found on the surface of multiple myeloma cells, to prevent cancer cells’ growth and to eliminate them. It was originally developed by Genmab, and licensed to Janssen in August 2012.

The approval was based on data from the open-label, multicenter CASSIOPEIA Phase 3 trial (NCT02541383). The study was designed to test the effects of Darzalex in combination with standard pre-transplant therapy (the VTd combo) in a group of multiple myeloma patients who had not received any prior treatment but were eligible for an ASCT.

The trial, which enrolled 1,085 people, is being conducted in two parts (it concludes in August 2024). In part one, researchers are testing whether adding Darzalex to standard VTd improves the chances of cancer eradication, compared to VTd alone. Here, treatment is given as preparation for the stem cell transplant, and then as a consolidation therapy.

In part two, all who responded to treatment will be reassigned to either maintenance therapy with Darzalex, given every eight weeks for up to two years, or kept on observation with no further treatment.

Genmab announced topline data from the first phase of the trial in October 2018, showing that pre-treatment with Darzalex plus VTd increased the proportion of patients whose cancer disappeared following a stem cell transplant from 20.3% to 28.9%.

More details regarding this topline data were announced by the company at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, and simultaneously published in The Lancet.

These new data revealed that, at a median follow-up of 18.8 months, the Darzalex combo lowered the risk of disease progression or death by 53% compared to VTd alone.

After consolidation therapy, the Darzalex combo also increased the percentage of patients achieving complete (39% versus 26%) or partial (83% versus 78%) cancer eradication compared to VTd alone.

The most common adverse events reported during the study included infusion reactions, nausea, fever, upper respiratory tract infections, and bronchitis. In patients receiving Darzalex, infusion reactions were reported in about a third of participants (35%).

“The pivotal Phase 3 CASSIOPEIA study is one of the largest transplant studies ever conducted in multiple myeloma, and the largest study conducted with daratumumab,” Philippe Moreau, MD, principal investigator and head of the Hematology Department at the University Hospital of Nantes, France, said in a press release.

“It’s important that patients get a deep response from their frontline therapy, and CASSIOPEIA demonstrates that the addition of daratumumab to VTd before and after transplant markedly increased depth of response compared to VTd alone for patients with newly diagnosed multiple myeloma,” Moreau said.

The FDA had placed Janssen’s request for approval, called a supplemental Biologics License Application (sBLA), under priority review. The application was submitted earlier this year, supported by data from CASSIOPEIA.

It marks a new approval for Darzalex, used alone or in combination, in this cancer. Janssen announced that Darzalex, plus a standard therapy, was approved by the FDA in June 2019 to treat newly diagnosed multiple myeloma patients who are not eligible for an ASCT, based on data from the MAIA Phase 3 trial (NCT02252172).

“The Darzalex clinical development program has led to many important firsts, but more importantly, it has generated key insights and understanding into the biology and treatment of multiple myeloma,” Craig Tendler, MD, vice president of Clinical Development and Global Medical Affairs, Oncology, at Janssen Research & Development, said in the release.

“Today’s milestone marks the seventh FDA approval in less than four years for Darzalex, and the third for newly diagnosed patients. Yet our work is far from over, as we are committed to discovering and developing innovative treatments like Darzalex for the benefit of patients facing a multiple myeloma diagnosis,” he added.