FDA Approves Daratumumab Combo for New First-Line Use

Nick Mulcahy

September 27, 2019

The US Food and Drug Administration (FDA) has approved daratumumab (Darzalex, Janssen) in combination with bortezomib (Velcade, Takeda), thalidomide (Thalomid), and dexamethasone (VTd) for newly diagnosed patients with multiple myeloma who are eligible for autologous stem cell transplant (ASCT).

It is the seventh indication in multiple myeloma for the drug.

The approval is based on efficacy and safety results from the CASSIOPEIA study, which included 1085 newly diagnosed patients with a median age of 58 years. In the phase 3 trial, adding daratumumab to VTd before and after ASCT resulted in a higher stringent complete response (sCR) rate, which was the primary endpoint, and superior progression-free survival (PFS) compared with VTd alone.

"The pivotal…study is one of the largest transplant studies ever conducted in multiple myeloma, and the largest study conducted with daratumumab," Philippe Moreau, MD, from the University Hospital of Nantes, France, said in a press statement. He is the trial's principal investigator.

"It's important that patients get a deep response from their front-line 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 explained.

Study results showed that the sCR rate after consolidation was significantly higher in the daratumumab-VTd group compared with VTd alone (29% vs 20%; odds ratio, 1.60; P = .0010). The daratumumab combination at a median follow-up of 18.8 months resulted in a 53% reduction in the relative risk for disease progression or death compared with VTd alone (hazard ratio, 0.47; P < .0001).

The most frequent adverse reactions (>20% with at least 5% greater frequency in the daratumumab-combination group) were infusion reactions, nausea, pyrexia, upper respiratory tract infection, and bronchitis, according to Janssen.

Serious adverse reactions with a more than 2% greater incidence in the daratumumab-combination group compared with the VTd group were bronchitis (2% vs <1%) and pneumonia (6% vs 4%), respectively. In the daratumumab-combination group, infusion-related reactions occurred in 35% of patients.

The CASSIOPEIA study was supported by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen.

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