Photo courtesy of Janssen
Daratumumab (Darzalex)
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended broadening the existing marketing authorization for daratumumab (Darzalex).
The CHMP is recommending approval for daratumumab in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant.
The CHMP’s recommendation will be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the European Union, Norway, Iceland, and Liechtenstein.
The EC usually makes a decision within 67 days of the CHMP’s recommendation.
Daratumumab already has EC approval for the following indications:
- For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, to treat adults with MM who have received at least 1 prior therapy
- As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.
The CHMP’s recommendation to expand the existing marketing authorization for daratumumab is based on results from the phase 3 ALCYONE (MMY3007) study.
Results from this study were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.
ALCYONE enrolled 706 patients with newly diagnosed MM who were not eligible for high-dose chemotherapy with autologous stem cell transplant. Patients were randomized to receive VMP or daratumumab plus VMP (D-VMP).
The overall response rates were 91% in the D-VMP arm and 74% in the VMP arm (P<0.0001). Rates of complete response were 43% and 24%, respectively. Rates of minimal residual disease negativity were 22% and 6%, respectively.
The median progression-free survival (PFS) was not reached in the D-VMP arm and was 18.1 months in the VMP arm. The 12-month PFS was 87% and 76%, respectively. The 18-month PFS was 72% and 50%, respectively.
The most common treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (50% and 53%), thrombocytopenia (49% and 54%), anemia (28% and 38%), peripheral sensory neuropathy (28% and 34%), upper respiratory tract infection (26% and 14%), diarrhea (24% and 25%), pyrexia (23% and 21%), and nausea (21% and 22%).
Infusion-related reactions occurred in 28% of patients in the D-VMP arm and 0% of those in the VMP arm.
The rate of grade 3/4 infections was higher in the D-VMP arm than the VMP arm—23% and 15%, respectively. In both arms, most infections resolved.
The most common grade 3/4 treatment-emergent adverse events (in the D-VMP and VMP arms, respectively) were neutropenia (40% and 39%), thrombocytopenia (34% and 38%), and anemia (16% and 20%).
The rate of discontinuation due to adverse events was 5% in the D-VMP arm and 9% in the VMP arm.