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EU Application Filed for Daratumumab in Newly Diagnosed, Transplant-Eligible Myeloma

Gina Columbus @ginacolumbusonc
Published: Wednesday, Mar 27, 2019

Jan van de Winkel, PhD
Jan van de Winkel, PhD
A Type II variation application has been submitted to the European Medicines Agency for the 4-drug regimen of daratumumab (Darzalex), bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone as a treatment for patients with newly diagnosed multiple myeloma who are eligible to undergo autologous stem cell transplant (ASCT).1

The submission is based on part 1 from the phase III CASSIOPEIA (MMY3006) trial, which demonstrated a 28.9% stringent complete response (sCR) in patients who received the quadruplet versus 20.3% in patients who were treated with bortezomib, thalidomide, and dexamethasone (VTd) alone after induction and consolidation therapy (odds ratio, 1.60; 95% CI, 1.21-2.12; P ≤.001).2

“With this submission we move another step closer to potentially expanding the Darzalex label. This gives us hope that a new population of patients with multiple myeloma in first line may be able to gain access to Darzalex,” said Jan van de Winkel, PhD, chief executive officer of Genmab, in a press release. Genmab previously granted Janssen an exclusive global license to develop, manufacture, and commercialize daratumumab.

In the open-label, multicenter, phase III CASSIOPEIA study (NCT02541383), 1085 patients with newly diagnosed, previously untreated symptomatic multiple myeloma who were eligible for high-dose chemotherapy and ASCT were enrolled. Patients were first randomized to receive 4 cycles of induction therapy with VTd alone or in combination with daratumumab at 16 mg/kg, high-dose therapy, and ASCT, and then consolidation therapy with VTd alone for 2 cycles or combined with 16 mg/kg of daratumumab.

To be eligible for enrollment, patients must have had previously untreated myeloma that is eligible for high-dose chemotherapy and ASCT, as well as an ECOG performance status of 0 to 2. Those who had primary amyloidosis, plasma cell leukemia, or smoldering multiple myeloma; prior or concurrent exposure to systemic therapy or stem cell transplant; 10-year history of cancer; known chronic obstructive pulmonary disease or moderate to severe asthma; or other interfering comorbidities were excluded.

The primary endpoint of part 1 of this trial was proportion of patients who achieved sCR. Part 1 results also showed that the safety profile of daratumumab in combination with VTd is consistent with the known profiles of VTd, which is used in patients receiving ASCT, as well as the known tolerability of daratumumab.

In the second part of CASSIOPEIA, which is ongoing, patients who achieved a partial response or better in part 1 of the trial will then undergo a second randomization to either receive maintenance daratumumab at 16 mg/kg every 8 weeks for up to 2 years or observation. The primary endpoint of this phase is progression-free survival (PFS).

Secondary endpoints include time to progression, proportion of post-ASCT/consolidation CR rate, proportion of post-ASCT/consolidation minimal residual disease negativity, proportion of post-induction sCR, PFS2, and overall survival.

Full findings of CASSIOPEIA are slated to be presented and published later in 2019. The trial was sponsored by the French Intergroupe Francophone du Myeloma in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology.

In March 2019, Janssen submitted a supplemental biologics license application to the FDA for daratumumab in combination with bortezomib, thalidomide, and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant.3

This application announcement follows another sBLA submission, also in March 2019, for daratumumab in combination with lenalidomide (Revlimid) and dexamethasone as a treatment for patients with newly diagnosed multiple myeloma who are ineligible for ASCT.


  1. Genmab Announces European Regulatory Submission for Daratumumab in Combination with Bortezomib, Thalidomide and Dexamethasone in Frontline Multiple Myeloma. Genmab. Published March 27, 2019. Accessed March 27, 2019.
  2. Genmab Announces Positive Topline Results in Phase III CASSIOPEIA Study of Daratumumab in Front Line Multiple Myeloma. Genmab. Published October 21, 2018. Accessed March 26, 2019.
  3. Janssen Submits Application for DARZALEX (daratumumab) Combination Therapy to U.S. FDA for Newly Diagnosed, Transplant Eligible Patients with Multiple Myeloma. Janssen. Published March 26, 2019. Accessed March 26, 2019.

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