Carfilzomib (Kyprolis, Onyx Pharmaceuticals, South San Francisco, CA) is a proteasome inhibitor that recently received accelerated FDA approval as single-agent treatment for relapsed or refractory multiple myeloma (RRMM),1 as well as designation as a “Preferred Regimen” for salvage therapy according to the National Comprehensive Cancer Network (NCCN) guidelines.2 Carfilzomib differs structurally and mechanistically from bortezomib; it functions by irreversibly inhibiting chymotrypsin-like activity of the constitutive proteasome and the immunoproteasome and offers a novel treatment option for patients with advanced MM.3
Carfilzomib (Kyprolis, Onyx Pharmaceuticals, Inc, South San Francisco, CA) is a selective proteasome inhibitor that irreversibly binds to active sites within the proteolytic core of the 26S proteasome, resulting in inhibition of proteasome activity. Preclinical studies have shown carfilzomib inhibits tumor growth and promotes tumor cell death, with sustained proteasome inhibition for more than 48 hours when using a consecutive-day dosing regimen.1-4
ES has received 5 prior lines of therapy, with progression of disease documented on her most recent therapy with a rise in SPEP from 1.3 to 2.2 g/dL and in UPEP from 556 to 1342 mg/24 hours. The current clinical considerations include anemia, renal insufficiency, and PN grade 1 with pain.
It is estimated that this year alone, approximately 21,000 individuals in the United States will be diagnosed with multiple myeloma (MM), and more than 10,000 deaths will be attributed to the disease.1 Response rates and survival have improved considerably over the past several decades, due in large part to the use of high-dose chemotherapy, stem cell transplantation, and the development and approval of the targeted agents thalidomide, lenalidomide, and bortezomib.2 Although these advances have resulted in prolonged remissions and better quality of life, virtually all
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