Myeloma is a type of cancer that affects immune cells called B-cells. Although no cure is currently available for myeloma, several treatments can help reduce B-cell proliferation and minimize the severity of symptoms.
Most therapeutic strategies for myeloma involve using a combination of the treatments below.
Chemotherapy agents are medications that stop the growth of cancer cells by either killing them or inhibiting their division.
Anthracyclines such as doxorubicin and idarubicin inhibit an enzyme involved in DNA replication known as topoisomerase 2. Etoposide is another topoisomerase 2 inhibitor that leads to DNA breakage in cancer cells.
Compounds such as cisplatin and cytarabine bind to DNA and cause cell death. Cisplatin prevents DNA repair mechanisms from working while cytarabine is thought to act by inhibiting a DNA replication enzyme called DNA polymerase A.
Immunomodulatory treatments work through several mechanisms such as boosting the function of immune cells called T-cells and natural killer (NK) cells, suppressing angiogenesis or the formation of new blood vessels to cut off the nutrient supply to the tumor, and decreasing the production of cell signaling molecules. Immunomodulatory treatments are usually prescribed in combination with other treatments, such as steroids and proteasome inhibitors.
Immunomodulatory treatments approved by the U.S. Food and Drug Administration (FDA) for the treatment of myeloma include Thalomid (thalidomide) and its derivatives, Revlimid (lenalidomide), and Pomalyst (pomalidomide).
Proteasome inhibitors work by targeting the protein breakdown and recycling machinery of the cell called the proteasome. Velcade (bortezomib), Kyprolis (carfilzomib), and Ninlaro (ixazomib) are proteasome inhibitors approved by the FDA to treat myeloma. They are often used in combination with steroids and immunomodulatory treatments.
CD38 inhibitors are a class of medication that target the CD38 protein, which is found abundantly on the surface of myeloma cells. The binding of the medicines to the CD38 protein results in the inhibition of tumor growth and induces cell death.
Histone deacetylase inhibitors
Histone deacetylase (HDAC) inhibitors are anti-cancer agents that work by inhibiting the activity of the HDAC enzyme. HDACs remove acetyl groups from a class of protein called histones and alter the interaction between histones and DNA. Inhibiting the activity of HDAC helps turn on tumor suppressor genes and control cell division.
Farydak (panobinostat) is an FDA-approved HDAC inhibitor for myeloma patients who have previously received bortezomib and an immunomodulatory treatment.
Signaling lymphocytic activation molecule (SLAM) F7 is a receptor that is abundantly present on myeloma cells as well as on other cells of the immune system, such as NK cells.
Empliciti (elotuzumab) is a SLAMF7 regulating antibody that is given in combination with an immunomodulatory treatment and steroid to treat relapsed or refractory multiple myeloma. It works by binding to the SLAMF7 receptors on myeloma cells and making them vulnerable to destruction by NK cells.
Inhibitors of nuclear export
Inhibitors of nuclear export are compounds that bind to a protein called XPO1 (exportin 1) and block its activity. This results in tumor suppressor genes remaining within the nucleus and stopping cell growth.
Xpovio (selinexor) is an inhibitor of nuclear export that has received accelerated FDA approval.
Autologous hematopoietic stem cell transplantation
Autologous hematopoietic stem cell transplant (AHSCT) is the process of replacing erroneous hematopoietic stem cells (HSCs) in the bone marrow by growing patient-derived HSCs in the laboratory and transplanting them back to the patient’s body to reset HSC development. AHSCT is a multi-step process that is often combined with chemotherapy and immunomodulatory treatment.
Human monoclonal antibodies
Xgeva (denosumab) is an FDA-approved antibody that binds to bone cells called osteoclasts and prevents bone tissue breakdown. Xgeva is designed to prevent bone fractures and other skeletal-related events in myeloma patients.
Apart from these, several experimental treatments for myeloma are under various stages of development.
Last updated: Jan. 21, 2020
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