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Prashant Kapoor, MD, FACP


Pros and Cons of BCMA-Targeting Treatment of Multiple Myeloma

By: Victoria Kuhr, BA
Posted: Tuesday, May 31, 2022

B-cell maturation antigen (BCMA) appears to be an ideal molecule for targeted immunotherapeutics for patients with multiple myeloma. Mehdi Talebi, PhD, of Tabriz University of Medical Sciences, Iran, and colleagues observed that the higher expression of BCMA on disease cells in comparison with normal cells makes it a relatively exclusive marker for myeloma. These study findings were published in the Journal of Translational Medicine.

BCMA has the highest level of B-cell maturation observed in the plasma line. It modulates membrane proteins, which keeps the protein on the cell membrane. Additionally, it aids in regulating plasma cell function through ligand binding control, promotes cell survival, and acts as an antibody secretion facilitator in the Golgi apparatus. Treatment with monoclonal antibodies targeting BCMA has a longer half-life than other anti–multiple myeloma drugs in ongoing and completed clinical trials combined with antibody-drug conjugates. This combination traps malfunctioning immune cells and provides fewer side effects than other targeted treatments, according to the authors.

In contrast to BCMA exclusivity to multiple myeloma, other gene expressions that appear in multiple myeloma also appear in normal cells and tissues. For example, the CD38 expression level is constant during the stages of multiple myeloma, but CD138 expression elevates during refractory and progressive stages. CD138 is expressed on normal tissues of hepatocytes, gastrointestinal goblet and columnar cells, and squamous epithelium. Additionally, CD38 is expressed on hematopoietic cells, Purkinje cells, and lung smooth muscle cells. Mucin 1 expression can be seen in solid tumors such as breast and colon cancers as well as numerous normal tissues such as in the respiratory system, gastrointestinal tract, kidney and urinary tracts, and female reproductive tissue. These few gene-expression examples illustrated the limitations of its being a specific marker for myeloma when it is seen in various other tissues and diseases.

Disclosure: The study authors reported no conflicts of interest.

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