Is Kyprolis a chemo drug and how does it work?
Kyprolis (carfilzomib) is from a class of medicines called proteasome inhibitors, which are targeted therapies for cancer. Kyprolis is not a chemotherapy, which are cancer treatments that are cytotoxic or cytostatic.
Kyprolis is used to treat multiple myeloma, which is a cancer of plasma cells (a type of white blood cell). Plasma cells are found in the soft tissue inside bones called bone marrow. They are a key part of the immune system and produce antibodies that fight and kill foreign invaders. When a person has multiple myeloma, their plasma cells grow out of control.
Kyprolis is a targeted therapy that is used:
- as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
- for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with
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How does Kyprolis work in patients with multiple myeloma?
Kyprolis works by blocking proteasome, which normally breaks down damaged or unneeded proteins within cells. This means that more abnormal proteins build up in the cancer cells, which causes the cancer cells to die.
On a more technical level, Kyprolis is a tetrapeptide epoxyketone proteasome inhibitor. It has:
- Antiproliferative activity, which means that it inhibits the growth of cells.
- Pro-apoptotic activity, which means that it encourages or causes cells to self-destruct.
Proteasomes work via the ubiquitin-proteasome pathway (UPP) to break down or degrade many cellular proteins.
Defects within the UPP are associated with the development of multiple myeloma and researchers have found that treatment with proteasome inhibitors, such as Kyprolis, leads to the accumulation of mis-folded monoclonal immunoglobulins (Ig) in plasma cells. This stresses the cells and results in the activation of the unfolded protein response (UPR) pathway. When the plasma cells are put under prolonged stress due to treatment with a proteasome inhibitor, activation of UPR stops the usual cell cycle process and induces apoptosis or cell death. Importantly, apoptosis induced by this manner targets the multiple myeloma plasma cells with high Ig production.
References
- Kyprolis Package Insert. https://www.drugs.com/pro/kyprolis.html
- American Cancer Society. What is multiple myeloma? [Accessed July 14, 2020]. Available online at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html.
- Livneh I, Cohen-Kaplan V, Cohen-Rosenzweig C, et al. The life cycle of the 26S proteasome: from birth, through regulation and function, and onto its death. Cell Res 26, 869–885 (2016). https://doi.org/10.1038/cr.2016.86.
- Kubiczkova L, Pour L, Sedlarikova L, Hajek R, Sevcikova S. Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma. J Cell Mol Med. 2014;18(6):947-961. doi:10.1111/jcmm.12279.
- Kuhn DJ, Chen Q, Voorhees PM, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007;110(9):3281-3290. doi:10.1182/blood-2007-01-065888.
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