By John Burke, M.D.
For the past few years, researchers have been working on developing monoclonal antibodies to treat multiple myeloma. Finally, the approval of at least a couple of such antibodies appears to be around the corner.
To provide some background. Monoclonal antibodies are proteins that bind to other proteins. In cancer treatment, monoclonal antibodies can be used to bind to proteins that are on the surface of cancer cells. The result is that the cancer cells can be killed by the immune system, or even by the antibody binding process itself. The image below provides a nice picture of what monoclonal antibodies look like and how they bind to the surface of cancer cells.
Monoclonal antibodies have taken hold in many different kinds of cancers, including non-Hodgkin lymphoma, chronic lymphocytic leukemia, breast cancer, and stomach cancer, but, so far, no monoclonal antibodies have been very helpful in multiple myeloma.
That is likely to change soon. A protein called SLAMF7, which stands for “signaling lymphocytic activation molecule F7,” is expressed on myeloma and natural killer cells, but not on normal tissues. Elotuzumab is a monoclonal antibody that targets SLAMF7. This week, the New England Journal of Medicine has published a study demonstrating that elotuzumab has significant activity in patients with multiple myeloma. In the study, 646 patients with relapsed myeloma were randomly assigned to receive lenalidomide (Revlimid) and dexamethasone alone or with elotuzumab. Lenalidomide and dexamethasone were administered orally, and elotuzumab was administered intravenously weekly for 2 months, then every other week thereafter.
Patients treated with elotuzumab experienced a 30% reduction in the risk of disease progression or death compared with patients not treated with elotuzumab. The response rate was also higher in the elotuzumab group (79%) than in the other group (66%).
There did not seem to be much difference in the side effects reported by the two groups of patients. Infusion reactions like chills occurred in 10% of patients treated with elotuzumab, usually during the first infusion. Patients treated with elotuzumab tended to have reduced lymphocyte counts, though this did not seem to lead to an increased risk of serious infections.
These results are very promising, and suggest that monoclonal antibodies may finally assume a role in the treatment of patients with myeloma. The relative lack of toxicity of elotuzumab certainly makes one wonder whether it could be added to induction regimens used early in the disease to improve long-term outcomes, but that hypothesis will require further study. There is great hope that the FDA will approve elotuzumab for myeloma patients soon.
Other monoclonal antibodies are also on the horizon for myeloma. One called daratumumab targets a protein called CD38, appears quite promising, and is undergoing extensive research. Other CD38-targeting antibodies are also under study.
The good news for myeloma patients is that monoclonal antibodies are soon to come!