Dr. Joesph Mikhael: How does an antibody identify myeloma cells but leave the other cells alone? Both monoclonal and bispecific antibodies are designed to specifically attach to a precise antigen on the surface of the myeloma cell. By selecting antigens that are specific to myeloma cells and not expressed on normal cells, these antibodies can refrain from damaging those healthy cells. The key antigens we currently target include BCMA, GPRC5D, and FcRH5.
What is the status of bispecific therapy? Well, this is a very exciting area of research in multiple myeloma right now. There are over 12 bispecifics in development in myeloma, some engaging T-cells and others engaging natural killer cells. They also attach to the myeloma cells through those different antigens of BCMA, GPRC5DD and FcRH5. Interestingly, even trispecific antibodies are being developed that have three arms, two that attach to the myeloma cell, and another that attaches to the immune cell.
We have now seen the approval of Teclistamab, the first bispecific antibody approved in myeloma, both in Europe and in the United States. It attaches to myeloma cells via the BCMA antigen and to T-cells via the CD3 antigen. It was tested in patients with heavily treated multiple myeloma, showing a response rate of over 60% in those patients. It will initially be used in heavily relapsed multiple myeloma. Other key agents we expect to see soon include Talquetamab, which targets GPRC5D and Elranatamab, which targets BCMA.
In summary, bispecific antibodies are a sophisticated form of immunotherapy in myeloma. They have the unique capacity to identify myeloma cells and directly engage immune cells to destroy those myeloma cells. They carry the risks of cytokine release syndrome, neurological side effects and infections, but they're very likely to revolutionize the way we treat multiple myeloma.
