Carfilzomib (Kyprolis)

General information

Class/mechanism: Second-generation proteasome inhibitor that interferes with degradation of ubiquitinated proteins by binding irreversibly to the 20S proteasome, which is the proteolytic core particle inside the 26S proteasome. This disrupts normal homeostatic mechanisms, leading to impaired tumor proliferation, apoptosis/cell death.

Route: IV
Extravasation: no information
NDC: NDC 76075-101-01; NDC 76075-0101-01

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, Medscape, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• Multiple myeloma
• Waldenström macroglobulinemia

Patient drug information

• Brief patient counseling information is available in the Carfilzomib (Kyprolis) package insert.
• Carfilzomib (Kyprolis) patient drug information (Chemocare)
• Carfilzomib (Kyprolis) patient drug information (UpToDate)

History of changes in FDA indication

• 7/20/2012: Received accelerated approval for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. (Based on PX-171-003-A1)
• 7/24/2015: Accelerated approval in combination with lenalidomide and dexamethasone for the treatment of patients with relapsed multiple myeloma who have received one to three prior lines of therapy. (Based on ASPIRE)
• 1/21/2016: Approved in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. (Based on ENDEAVOR and ARROW)
• 1/21/2016: Approved as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. (Based on PX-171-004 bortezomib-naive and PX-171-007)
• 8/20/2020: Approved in combination with daratumumab and dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. (Based on CANDOR and EQUULEUS)

Post-marketing concerns

• January 2015: New safety information concerning posterior reversible encephalopathy syndrome (PRES), based on several case reports.

Also known as

• Code name: PR-171
• Generic name: CFZ
• Brand names: Carfilnat, Kyprolis