Proteasome Inhibitors In Multiple Myeloma
Proteasome inhibitors are medications that target proteasomes inside the cells. Proteasomes digest unneeded or damaged proteins. Proteasome inhibitors block proteasomes inside cells causing a buildup of proteins that leads to cell death.
Proteasome inhibitors are used in multiple myeloma across the board as part of induction/consolidation therapy maintenance as well as treatment at relapse.
FDA-approved proteasome inhibitors are bortezomib, which can be given intravenously or subcutaneously; carfilzomib, which is given intravenously; and ixazomib which is oral.
Bortezomib in combination with lenalidomide (immunomodulator) and dexamethasone is the most common regimen used in newly diagnosed myeloma patients.
Bortezomib is associated with a higher incidence of peripheral neuropathy. In order to decrease the incidence of neuropathy which could be as high as 30% if bortezomib is given subcutaneously instead of intravenously, subcutaneously and instead of twice a week, once a week the incidence of high grade neuropathy drops to 8%. In patients with high-risk disease maintenance with bortezomib showed improved disease free survival.
Carfilzomib is a second generation proteasome inhibitor. Carfilzomib has less peripheral neuropathy compared with bortezomib. Carfilzomib is currently being studied with lenalidomide and dexamethasone. The most common side effects with carfilzomib are anemia thrombocytopenia, fatigue, edema, and diarrhea.
Ixazomib is an oral proteasome inhibitor given on a weekly basis that in combination with lenalidomide and dexamethasone has had the same efficacy as with RUD.
Ixazomib can be used as maintenance treatment as well. The most common side effects from ixazomib are low platelet count, diarrhea, swelling and rash. The liver function test needs to be monitored.