Carfilzomib: a novel agent for multiple myeloma

• Published in: Journal of pharmacy and pharmacology 2013-08, Vol.65 (8), p.1095-1106
• Main Author: Redic, Kimberly
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; carfilzomib; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Interactions; Drug therapy; Humans; Molecular Structure; multiple myeloma; Multiple Myeloma - drug therapy; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Oligopeptides - pharmacokinetics; Oligopeptides - therapeutic use; proteasome inhibitor; Proteasome Inhibitors - administration & dosage; Proteasome Inhibitors - adverse effects; Proteasome Inhibitors - pharmacokinetics; Proteasome Inhibitors - therapeutic use
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12072

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/m2 in cycle 1; 27 mg/m2 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.