FDA Approves Darzalex Combo as Frontline Treatment for Myeloma

The combination use of Darzalex with bortezomib, thalidomide, and dexamethasone was approved for transplant-eligible patients with multiple myeloma.

The FDA approved the combination use of daratumumab (Darzalex) plus bortezomib (Velcade), thalidomide and dexamethasone (Vtd) as a frontline treatment for patients who are eligible for autologous stem cell transplant (ASCT).

This is the third approval to include Darzalex for patients with newly-diagnosed multiple myeloma, said Jan van de Winkel, PhD, chief executive officer, Genmab, in a press release.

The agency based its approval on the results of the randomized, multi-center phase III CASSIOPEIA study of 1,085 patients enrolled across 111 European sites between 2015 and 2017. Results were previously published in The Lancet.

In part 1 of the trial, patients were first randomized to receive 4 cycles of induction therapy with VTd alone (n = 542) or in combination with daratumumab (D-Vtd; n = 543) at 16 mg/kg, high-dose therapy (melphalan), and ASCT, and then consolidation therapy with VTd alone for 2 cycles or combined with daratumumab at 16 mg/kg.

The primary endpoint for the first part of the study gauged stringent complete response 100 days after stem cell transplantation. The second part of the study is focusing on maintenance, and is ongoing.

At day 100 after ASCT, 29% of patients in the D-VTd group and 20% of patients in the VTd group among the intention-to-treat population had achieved a stringent complete response (OR, 1.60; 95% CI, 1.21–2.12, P = .001). In addition, 39% of patients in the D-VTd group, compared with 26% in the VTd group, achieved a complete response or better.

“D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety,” the authors further concluded in the study. “CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma.”

However, median progression-free survival from the first transmoization was not reached in either group, according to the paper.

Adverse events included grade 3/4 neutropenia, lymphopenia, and stomatitis.

Additional phase III studies are ongoing or planned to use daratumumab in cancers and other diseases, including NKT-cell lymphoma, B-cell and T-cell acute lymphoblastic leukemia, as well as amyloidosis, the press release said.


Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019:394(10192):29-38. doi:10.1016/S0140-6736(19)31240-1.