Kimberly Redic1. 1. University of Michigan College of Pharmacy, Ann Arbor, MI, USA; University of Michigan Health System, Ann Arbor, MI 48109, USA. kredic@umich.edu
Abstract
OBJECTIVES: Carfilzomib is a new agent for the treatment of relapsed and refractory multiple myeloma (MM). This article presents a comprehensive overview of the pharmacokinetics, pharmacodynamics, dosing schedule, safety, efficacy, preparation and administration of carfilzomib, and its role in treating MM patients. KEY FINDINGS: Carfilzomib is a selective proteasome inhibitor that differs structurally and mechanistically from bortezomib. In patients' whole-blood and peripheral-blood mononuclear cells, carfilzomib inhibited proteasomal and immunoproteasomal activity by 70-80%. Approved carfilzomib dosing is based on body surface area, and is given on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle (20 mg/m(2) in cycle 1; 27 mg/m(2) in cycle 2+). Premedication with dexamethasone and adequate hydration are recommended to reduce the risk of adverse events. The median t1/2 of carfilzomib is short (0.29-0.48 h), with no accumulation detected between doses. In clinical studies in relapsed and refractory MM. and in combinations in newly diagnosed MM, single-agent carfilzomib demonstrated significant durable activity, good tolerability and a favourable safety profile, supporting its extended use. CONCLUSIONS: Carfilzomib represents an important addition to the treatment armamentarium for patients with relapsed and/or refractory MM, and studies are underway evaluating the role of single-agent carfilzomib in additional clinical settings as well as in different combinations.
OBJECTIVES:Carfilzomib is a new agent for the treatment of relapsed and refractory multiple myeloma (MM). This article presents a comprehensive overview of the pharmacokinetics, pharmacodynamics, dosing schedule, safety, efficacy, preparation and administration of carfilzomib, and its role in treating MM patients. KEY FINDINGS:Carfilzomib is a selective proteasome inhibitor that differs structurally and mechanistically from bortezomib. In patients' whole-blood and peripheral-blood mononuclear cells, carfilzomib inhibited proteasomal and immunoproteasomal activity by 70-80%. Approved carfilzomib dosing is based on body surface area, and is given on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle (20 mg/m(2) in cycle 1; 27 mg/m(2) in cycle 2+). Premedication with dexamethasone and adequate hydration are recommended to reduce the risk of adverse events. The median t1/2 of carfilzomib is short (0.29-0.48 h), with no accumulation detected between doses. In clinical studies in relapsed and refractory MM. and in combinations in newly diagnosed MM, single-agent carfilzomib demonstrated significant durable activity, good tolerability and a favourable safety profile, supporting its extended use. CONCLUSIONS:Carfilzomib represents an important addition to the treatment armamentarium for patients with relapsed and/or refractory MM, and studies are underway evaluating the role of single-agent carfilzomib in additional clinical settings as well as in different combinations.
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