Multiple myeloma is a haematological cancer in which plasma cells in the bone marrow proliferate excessively, leading to bone disease and systemic release of a monoclonal immunoglobulin that causes tissue damage, particularly in the kidney. While the outlook for patients has become more positive in the past 15 years, the cancer remains incurable with a median survival of about five years. It is estimated to cause around 10,000 deaths every year in the United States.
Last November, the FDA approved the first two therapeutic antibodies for relapsed or refractory multiple myeloma: Janssen's daratumumab, and Bristol-Myers Squibb's elotuzumab. These can be combined with current treatment regimens.
According to Vincent Rajkumar, M.D., a professor of medicine and hematologist at the Mayo Clinic, who was not involved in the development of the antibodies, this is exciting news for the field. “There's a real excitement in the field that we have the tools now to at least test the possibility that [multiple myeloma] might be cured.” Dr. Rajkumar discussed his insights with Nature Reviews Drug Discovery.
Daratumumab, licensed from Genmab, is a human monoclonal antibody that targets CD38 — a glycoprotein found in abundance on myeloma cells and expressed at low levels on normal myeloid cells, lymphoid cells, and some other tissues. Antibody binding not only engages immune cells to kill myeloma cells and triggers complement-dependent cytotoxicity, but also directly initiates apoptosis in targeted cells.
Elotuzumab is a humanized monoclonal antibody that hones in on signalling lymphocytic activation molecule F7 (SLAMF7; also known as CS1), a cell-surface glycoprotein found predominantly on myeloma cells, leading to antibody-dependent cell killing by immune effectors. The antibody, developed in partnership with AbbVie, also directly activates natural killer cells, adding to its cytotoxic effect.
With both antibodies brand new to treatment, clinicians will base their selection on patient's characteristics and the drugs' different profiles and costs. Owing to the single-agent activity of daratumumab, Dr. Rajkumar speculates that this agent will be the first port of call, and that “the fate of elotuzumab depends on how daratumumab fares.”