Study results show patients with newly diagnosed multiple myeloma showed a lower risk of disease progression or death with daratumumab added to the standard regimen of bortezomib, melphalan and prednisone, than patients who were treated without daratumumab in their drug combination.
Patients with newly diagnosed multiple myeloma showed a lower risk of disease progression or death with daratumumab (Darzalex, Janssen) added to the standard regimen of bortezomib (Velcade, Takeda), melphalan and prednisone, in a recent study, than patients who were treated without daratumumab in their drug combination.1
Phase 3 trial results recently published by the New England Journal of Medicine, focused on 706 randomly-assigned patients with new diagnoses of multiple myeloma and who were not eligible for stem cell transplantation. The patients received 9 cycles of bortezomib, melphalan and prednisone, either alone (control group) or with daratumumab, until disease progression.1
The 18-month progression-free survival rate was 71.6% (95% CI, 65.5-76.8), compared to 50.2% (95% CI, 43.2-56.7) in the control group, according to the study. Overall, the response rate was 90.9% in the daratumumab group and 73.9% in the control group. In the daratumumab group, 22.3% were negative for minimal residual disease, at a threshold of 1 tumor cell per 105 white cells, while 6.2% of patients in the control group reported the same.1
Daratumumab targets a protein, CD38, that is often overexpressed on multiple myeloma cells and also expressed on many types of immune cells.2 According to the National Cancer Institute, the drug is thought to work by killing tumor cells directly and by stimulating an immune response against cancer cells.
In previous studies, daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapses or refractory multiple myeloma.1 It was initially approved by the FDA, in November 2015, as a standalone cancer treatment for multiple myeloma patients whose disease has progressed after receiving at least 3 prior treatment regimens using standard combination therapies.2 The FDA later approved daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.3
In addition to lower risk of disease progression or death, the latest study concluded that the daratumumab-containing drug treatment was associated with more grade 3 or 4 infections. The rate of grade 3 or 4 infections was 23.1% in the daratumumab group and 14.7% in the control group, and the rate of discontinuation of treatment due to infections was 0.9% and 1.4%, respectively.1
According to the new trial results, the most common adverse effects of grade 3 or 4 were hematologic: neutropenia (in 39.9% of the patients in the daratumumab group and in 38.7% of those in the control group), thrombocytopenia (in 34.4 % and 37.6%, respectively) and anemia (in 15.9% and 19.8%, respectively). In addition, infusion-related reactions associated with daratumumab occurred in 27.7% of patients.1
Officials with the FDA are expected to decide on the application for daratumumab plus VMP by May 21, 2018, as part of the Prescription Drug User Fee Act.
The study was funded by Janssen Research and Development.