A phase 3 study of daratumumab in combination with lenalidomide and dexamethasone versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma has met its primary endpoint of improved progression-free survival (PFS) in a preplanned interim analysis (hazard ratio [HR], 0.37; P < 0.0001). Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, plans to engage in a dialogue with health authorities about the potential for a regulatory submission for this indication.
The POLLUX trial enrolled 569 patients with relapsed or refractory multiple myeloma. The patients were randomly assigned to receive either daratumumab combined with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid), or lenalidomide and dexamethasone alone.
Patients who were treated with daratumumab in combination with lenalidomide and dexamethasone had a 63% reduction in the risk of their disease progressing compared with those who did not receive daratumumab. The median PFS for patients treated with daratumumab in combination with lenalidomide and dexamethasone has not been reached, compared with an estimated median PFS of 18.4 months for patients who received lenalidomide and dexamethasone alone.
Daratumumab is a human immunoglobulin G1 kappa (IgG1k) monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab is believed to induce rapid tumor cell death through apoptosis and numerous immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity.
In addition, treatment with daratumumab results in a reduction of immune-suppressive myeloid-derived suppressor cells (MDSCs) and subsets of regulatory T cells (Tregs) and B cells (Bregs), all of which express CD38. These reductions in MDSCs, Tregs, and Bregs were accompanied by increases in the numbers of CD4-positive and CD8-positive T-cells in both the peripheral blood and bone marrow.
In the United States, daratumumab for injection for intravenous infusion is indicated for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent. Daratumumab is the first mAb to receive FDA approval to treat multiple myeloma.
Source: Genmab; May 18, 2016.