Myeloma (sometimes called multiple myeloma) is a cancer affecting a type of white blood cell called B-cells that normally produce antibodies to fight off infection and disease. In myeloma, these cells divide rapidly but do not produce normal antibodies, which weakens the immune system. Instead, they produce dysfunctional antibodies that can cause kidney damage, among other complications.
Myeloma cells are produced in the bone marrow like normal blood cells, and can travel through the bloodstream and accumulate elsewhere in the body.
What are proteasome inhibitors?
Proteasomes are protein complexes in the cell that are responsible for breaking down proteins and recycling their components. Because cancer cells divide so quickly and produce so much protein, proteasomes have to work overtime to keep the cell functioning.
Proteasome inhibitors target cancer cells by blocking the breakdown of proteins by the proteasome. Without functioning proteasomes, waste proteins build up within these cells, poisoning them and causing them to die.
Proteasome inhibitors to treat myeloma
Three proteasome inhibitors are approved to treat myeloma: Velcade (bortezomib), Kyprolis (carfilzomib), and Ninlaro (ixazomib).
Velcade is approved to treat myeloma and mantle cell lymphoma (another type of cancer affecting immune cells). It was initially developed by Myogenics, and brought to clinical trials by Millennium Pharmaceuticals, which was later acquired by Takeda.
Kyprolis is approved to treat refractory myeloma — myeloma that has not responded to two or more other treatments. It was initially licensed to Proteolix, which was acquired by Onyx Pharmaceuticals in 2009. Subsequently, Onyx was bought by Amgen.
Ninlaro was developed by Takeda and is used to treat myeloma in combination with Revlimid (lenalidomide) and dexamethasone in patients who have received at least one prior treatment for their multiple myeloma. Ninlaro is an oral medication that can be taken at home.
Experimental proteasome inhibitors
Several experimental proteasome inhibitors are currently under development.
Oprozomib (an oral next-generation carfilzomib) is being developed by Amgen. Marizomib is also under development by Triphase Accelerator.
Last updated: Nov. 5, 2019
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