Oncology
Carfilzomib
An irreversible proteasome inhibitor peptide used in relapsed multiple myeloma.
What it is
Carfilzomib (Kyprolis) is a tetrapeptide epoxyketone that binds the proteasome irreversibly, unlike bortezomib's reversible binding. It was developed partly to work in myeloma that had become resistant to bortezomib. It is a specialist cancer medicine given intravenously on a weekly schedule.
How it works
- 1
Covalently and irreversibly inhibits the chymotrypsin-like site of the proteasome.
- 2
Protein waste builds up in myeloma cells until they die.
- 3
Blocks NF-kappa-B signalling by preventing I-kappa-B breakdown.
- 4
Irreversible binding means the effect lasts until new proteasomes are made.
- 5
Its different chemistry allows activity in some bortezomib-resistant disease.
What it's studied for
Reported and studied effects
- Longer progression-free survival than standard comparator regimens in ASPIRE and ENDEAVOR
- Peripheral neuropathy less frequent than with bortezomib
- Cardiovascular events and hypertension, which require monitoring
- Infusion reactions, mitigated by premedication
Research protocol notes
Research context onlyResearch context only - a specialist cancer medicine. Regimens step from 20 mg per square metre on the first doses to 27 mg per square metre twice weekly, or up to 56 to 70 mg per square metre on a once-weekly schedule, in 28-day cycles with dexamethasone; trials tracked progression-free survival with blood pressure, cardiac and renal monitoring.
These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.
Possible side effects and contraindications
Safety profile
Possible side effects
- Hypertension and heart failure
- Cardiac events including arrhythmia
- Infusion reactions
- Fatigue
- Diarrhoea and nausea
- Thrombocytopenia and anaemia
- Pulmonary hypertension and dyspnoea
Contraindications and cautions
- Prior hypersensitivity
- Uncontrolled hypertension or recent cardiac events require assessment
- Severe liver impairment
- Pregnancy - harmful to the fetus
- Not for intrathecal use
A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.
Evidence assessment
Two large randomised phase 3 trials (ASPIRE and ENDEAVOR) with progression-free survival as the primary endpoint, and regulatory approval in the EU and US.
References
- 01Stewart et al., Carfilzomib, lenalidomide and dexamethasone for relapsed multiple myeloma (ASPIRE), NEJM 2015
- 02European Medicines Agency - Kyprolis product information
References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.
Related
Related peptides
Other entries in Oncology.