Carfilzomib
A peptide proteasome inhibitor for relapsed multiple myeloma, with a heart-risk warning
Carfilzomib is a synthetic four-amino-acid peptide with an epoxyketone warhead that shuts down the proteasome for good. Approved as Kyprolis in 2012, it is an intravenous chemotherapy drug for multiple myeloma that has come back or stopped responding.
Manufacturer's recommended dosing (FDA label): 20 mg/m² on cycle 1 day 1, then 70 mg/m², Days 1, 8 and 15 of each 28-day cycle, Intravenous, 30-minute infusion Details ↓
Recommended Dosing
Manufacturer's recommended dosing (FDA label)
From the prescribing information. Other doses studied, if any, are in the full dosing data below.
What is it?
Carfilzomib is a true small peptide drug, but it belongs on a hospital ward, not in a vial bought online. It is a chain of four modified amino acids ending in an epoxyketone, a reactive group that locks onto the proteasome, the machine cells use to break down used proteins; in laboratory studies it slowed and killed tumour cells. The FDA approved carfilzomib as Kyprolis in 2012, initially for patients whose myeloma had progressed after at least two earlier treatments, including bortezomib.
That first approval rested on a single-arm trial in heavily pretreated patients, a median of five earlier lines, where about a quarter responded. Randomised trials then moved it earlier. In ASPIRE, adding it to lenalidomide and dexamethasone lengthened progression-free survival from 17.6 to 26.3 months and, at the final analysis, median survival from 40.4 to 48.3 months. In ENDEAVOR, carfilzomib with dexamethasone doubled progression-free survival against bortezomib with dexamethasone and lengthened median survival by about nine months. CANDOR and IKEMA then added the antibodies daratumumab and isatuximab to it.
Its main safety problem is the heart and blood vessels. The label warns of new or worse heart failure, heart attack, cardiac arrest within a day of a dose, high blood pressure, pulmonary hypertension and kidney failure; heart failure occurred in 8% in its combination trials. A meta-analysis of 24 trials found cardiovascular events in 18.1% of patients, 8.2% severe, more often at higher doses. In ENDEAVOR, severe high blood pressure was three times as common as with bortezomib. In head-to-head trials it caused far less nerve damage than bortezomib.
Not every trial went its way. In heavily treated patients, carfilzomib alone did not lengthen survival compared with steroids and cyclophosphamide (FOCUS). In newly diagnosed patients it failed to beat bortezomib regimens in CLARION and ENDURANCE, with more heart and kidney problems, and the label now warns against its use with melphalan and prednisone in that setting. A smaller Italian trial did find deeper responses when it was added to lenalidomide in older patients.
Dosing is set by body surface area, with a lower first dose, fluids before the first cycle, dexamethasone beforehand, and blood clot prevention in combination regimens. A weekly schedule at a higher dose beat the older twice-weekly schedule in the ARROW trial. All of this is managed by a myeloma team; the drug has no use outside that setting.
Mechanism of Action
Carfilzomib is a tetrapeptide epoxyketone that irreversibly blocks the proteasome (Kyprolis label 12.1).
Proteasome
Binds irreversibly to the N-terminal threonine active sites of the 20S proteasome core (label 12.1).
Rapid breakdown
Cleared by peptidase cleavage and epoxide hydrolysis, with a half-life of 1 hour or less (label 12.3).
Heart and vessels
Cardiovascular events in 18.1% of patients across 24 trials, more often at higher doses (PMID 29285538).
Published Research
The studies behind carfilzomib, read from their PubMed abstracts: the pivotal and randomised trials, the failures, and the heart-safety analysis.
The trial behind the first approval
In 266 patients with relapsed and refractory myeloma after a median of five earlier lines, single-agent carfilzomib (20 then 27 mg/m² twice weekly) produced responses in 23.7% lasting a median 7.8 months; median survival was 15.6 months, and 12.4% had mostly mild nerve damage.
ASPIRE: added to lenalidomide and dexamethasone
In 792 patients with relapsed myeloma, adding carfilzomib raised median progression-free survival to 26.3 months from 17.6 and the response rate to 87.1% from 66.7%; severe adverse events were similar (83.7% against 80.7%) and quality of life was better.
ASPIRE: final survival
Median overall survival was 48.3 months with carfilzomib against 40.4 months, with the largest gain at first relapse; severe heart failure (4.3% against 2.1%) and high blood pressure (6.4% against 2.3%) were more common with carfilzomib.
ENDEAVOR: carfilzomib against bortezomib
In 929 patients, carfilzomib 56 mg/m² with dexamethasone gave a median progression-free survival of 18.7 months against 9.4 with bortezomib; serious adverse events were 48% against 36%, and severe high blood pressure 9% against 3%.
ENDEAVOR: survival update
After about 44 months of follow-up, median overall survival was 47.8 months with carfilzomib against 38.8 months with bortezomib, longer in every subgroup examined.
ARROW: once a week at a higher dose
In 478 patients, carfilzomib 70 mg/m² once weekly gave a median progression-free survival of 11.2 months against 7.6 for 27 mg/m² twice weekly; severe adverse events were 68% against 62%, and severe heart failure 3% against 4%.
CANDOR: adding daratumumab
In 466 patients, adding daratumumab to carfilzomib and dexamethasone cut the risk of progression or death (hazard ratio 0.63); severe adverse events were 82% against 74%.
IKEMA: adding isatuximab
In 302 patients, adding isatuximab to carfilzomib and dexamethasone cut the risk of progression or death (hazard ratio 0.53; median 19.15 months in the control arm); fatal adverse events were 3% in each arm.
FOCUS: alone against steroids
In 315 heavily treated patients, single-agent carfilzomib gave median survival of 10.2 months against 10.0 with low-dose steroids and cyclophosphamide, despite more responses (19.1% against 11.4%).
CLARION: no gain in new myeloma
In 955 newly diagnosed patients unfit for transplant, carfilzomib with melphalan and prednisone gave the same progression-free survival as the bortezomib regimen (22.3 against 22.1 months), with more kidney failure (13.9% against 6.2%) and heart failure (10.8% against 4.3%) but far less nerve damage.
ENDURANCE: not better than bortezomib up front
In 1,087 newly diagnosed patients, carfilzomib with lenalidomide and dexamethasone gave the same progression-free survival as bortezomib with the same drugs (34.6 against 34.4 months) with more treatment-related deaths (2% against under 1%), four of them cardiac.
EMN20: older patients, weekly dosing
In 82 newly diagnosed patients ineligible for transplant, in a trial stopped early, weekly carfilzomib with lenalidomide and dexamethasone left no detectable myeloma at two years in 60% against 0% without it, and lowered the risk of progression (hazard ratio 0.24).
Heart and blood-vessel risk
A meta-analysis of 24 trials (2,594 patients) found cardiovascular adverse events in 18.1% and severe ones in 8.2%; doses of 45 mg/m² or more were linked to severe events, and in randomised trials the risk was about twice that of control arms.
Review at the time of approval
This review summarises the trial data behind the 2012 US approval for myeloma that had progressed after at least two prior therapies, including bortezomib and an immunomodulatory drug, and gives practical advice for prescribers.
Dosing Data
Kyprolis is given by intravenous infusion, dosed by body surface area (capped at 2.2 m²), with a lower first dose, hydration and dexamethasone premedication in cycle 1. The label's three regimens are below.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
The approved product, as its label describes it:
- Kyprolis (carfilzomib injection): For injection: 10 mg, 30 mg or 60 mg lyophilized powder in single-dose vial for reconstitution. Forms the label lists: single-dose vials.
Source: Kyprolis (carfilzomib injection) label, section 3 (DailyMed version 59, effective June 18, 2025).
Mixing a vial: a worked example
Nothing to mix at home, and no syringe units to work out: Carfilzomib is prepared and given by clinical staff, by a cancer team in an infusion centre or hospital.
Its US label gives it as a timed infusion into a vein, with premedication and intravenous fluids around the first cycle's doses.
Source: Kyprolis (carfilzomib injection) label, section 2 (DailyMed version 59, effective June 18, 2025).
Storage before and after mixing
Before mixing or first use: “Storage and Handling Unopened vials should be stored refrigerated 2°C to 8°C (36°F to 46°F).” “Retain in original package to protect from light.”
After mixing or first use: “Discard any unused portion left in the vial.”
Source: Kyprolis (carfilzomib injection) label, sections 16 and 2 (DailyMed version 59, effective June 18, 2025).
How it is taken
As the approved label gives it: Intravenous, 30-minute infusion (Days 1, 8 and 15 of each 28-day cycle; Label: once weekly, with dexamethasone or daratumumab-dexamethasone); Intravenous, 10-minute infusion (Days 1, 2, 8, 9, 15 and 16 (cycles 1 to 12); days 1, 2, 15 and 16 from cycle 13; Label: twice weekly, monotherapy or with lenalidomide-dexamethasone); Intravenous (As for the regimen; Label: mild or moderate liver impairment).
Source: Manufacturer's recommended dosing (FDA label): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of 1 hour or less. After about five half-lives almost none is left.
How long the doses were given: Label: once weekly, with dexamethasone or daratumumab-dexamethasone: Until progression or unacceptable toxicity; Label: twice weekly, monotherapy or with dexamethasone, daratumumab or isatuximab: Until progression or unacceptable toxicity; Label: twice weekly, monotherapy or with lenalidomide-dexamethasone: With lenalidomide, stop after cycle 18.
When effects appear: unknown; no source on this page gives a time to effect for Carfilzomib. Results reported in the studies are under Published Research.
Source: half-life: Kyprolis prescribing information, section 12.3 (DailyMed set ea66eb30, version 59, effective June 18, 2025); Manufacturer's recommended dosing (FDA label), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Heart failure, heart attack and high blood pressure, more often than with comparator drugs; Kidney failure, especially with melphalan and prednisone; Low blood counts, especially anaemia and low platelets; Shortness of breath and blood clots in combination regimens; Less nerve damage than bortezomib. Full list and cautions ↓
When the label says to stop or get help:
- Cardiac Toxicities: Monitor for signs and symptoms of cardiac failure or ischemia. Withhold Kyprolis and evaluate promptly.
- Tumor Lysis Syndrome (TLS): Administer pre-treatment hydration. (2.1 ) Monitor for TLS, including uric acid levels and treat promptly.
- Pulmonary Toxicity, including Acute Respiratory Distress Syndrome, Acute Respiratory Failure, and Acute Diffuse Infiltrative Pulmonary Disease: Withhold Kyprolis and evaluate promptly.
- Infusion-related Reactions: Premedicate with dexamethasone. ( 2.1, 5.9 ) Hemorrhage: Fatal or serious cases of hemorrhage may occur, including gastrointestinal, pulmonary, and intracranial hemorrhage. Promptly evaluate signs and symptoms of blood loss.
Source: Kyprolis (carfilzomib injection) label, boxed warning and section 5 (DailyMed version 59, effective June 18, 2025); the Side Effects section below (“From the studies above”).
Interactions
- midazolam (a CYP3A substrate): carfilzomib inhibited CYP3A in human liver microsomes, but did not change midazolam pharmacokinetics in patients with solid tumours; because it is cleared mainly by peptidases and epoxide hydrolysis, CYP450 inhibitors or inducers are unlikely to change its exposure
Every peptide's record, with its source: the interaction matrix.
Source: human study, PMID 23118326.
Checking what you bought
Unknown: no published independent test of Carfilzomib products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Carfilzomib's expected mass, 719.9 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: FDA Approved (FDA-approved as Kyprolis (NDA 202714) for adults with relapsed or refractory multiple myeloma, in combination regimens after one to three prior lines and as a single agent after one or more (US prescribing information, DailyMed set ea66eb30, version 59)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
Warnings from the Kyprolis label (DailyMed set ea66eb30, version 59, effective June 18, 2025). It has no boxed warning and no contraindications.
Legal Status
Carfilzomib is an approved prescription drug in the US and authorised in the EU.
Frequently Asked Questions
?Is carfilzomib a peptide?
Yes: a synthetic chain of four modified amino acids with an epoxyketone at one end. It is a prescription myeloma drug given in an infusion centre, not a research peptide.
?How is it different from bortezomib?
Both block the proteasome, but carfilzomib binds irreversibly. In ENDEAVOR it doubled progression-free survival against bortezomib and caused little nerve damage, but more high blood pressure and heart problems.
?Why is the heart such a concern?
Its label warns of heart failure, heart attack and cardiac arrest, and a meta-analysis found cardiovascular events in about 18% of patients. Blood pressure and fluid status are checked throughout treatment.
?Is it used in newly diagnosed myeloma?
Its US label covers relapsed or refractory myeloma. Two large trials in new patients (CLARION and ENDURANCE) did not show a benefit over bortezomib regimens.
?How often is it given?
As an intravenous infusion once or twice a week for three weeks of each four-week cycle, by one of three label regimens.
?Why does it come up on peptide sites?
Because it is a peptide drug. That does not make it safe or useful outside cancer care; its doses come with mandatory fluids, premedication and monitoring.
References
- [fda-pi] Kyprolis (carfilzomib) for injection, US prescribing information, sections 1, 2, 11 and 12.3 (Onyx Pharmaceuticals; DailyMed set ea66eb30, version 59, effective June 18, 2025; read October 28, 2026).
- [other] PubChem CID 11556711, Carfilzomib: formula C40H57N5O7, molecular weight 719.9; ChEBI description: a synthetic tetrapeptide of morpholin-4-acetyl, L-2-amino-4-phenylbutanoyl, L-leucyl and L-phenylalanyl residues whose C-terminus is joined to an epoxyketone. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/11556711
- [clinical-trial] Dimopoulos MA, et al. "Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study." Lancet Oncol, 2016;17(1):27-38. PMID: 26671818.
- [review] Kortuem KM, et al. "Carfilzomib." Blood, 2013;121(6):893-7. PMID: 23393020.
- [other] European Medicines Agency, medicines list (JSON report, downloaded October 28, 2026): Kyprolis (carfilzomib): authorised, marketing authorisation date November 19, 2015.
- [fda] US FDA, Drugs@FDA (openFDA): KYPROLIS (carfilzomib), NDA 202714, Onyx Pharms Amgen; original approval July 20, 2012; marketing status Prescription. Read October 28, 2026.
- [clinical-trial] Siegel DS, et al. "A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma." Blood, 2012;120(14):2817-25. PMID: 22833546.
- [clinical-trial] Stewart AK, et al. "Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma." N Engl J Med, 2015;372(2):142-52. PMID: 25482145.
- [clinical-trial] Siegel DS, et al. "Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma." J Clin Oncol, 2018;36(8):728-734. PMID: 29341834.
- [clinical-trial] Orlowski RZ, et al. "Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups." Clin Lymphoma Myeloma Leuk, 2019;19(8):522-530.e1. PMID: 31160237.
- [clinical-trial] Moreau P, et al. "Once weekly versus twice weekly carfilzomib dosing in patients with relapsed and refractory multiple myeloma (A.R.R.O.W.): interim analysis results of a randomised, phase 3 study." Lancet Oncol, 2018;19(7):953-964. PMID: 29866475.
- [clinical-trial] Dimopoulos M, et al. "Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study." Lancet, 2020;396(10245):186-197. PMID: 32682484.
- [clinical-trial] Moreau P, et al. "Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial." Lancet, 2021;397(10292):2361-2371. PMID: 34097854.
- [clinical-trial] Hájek R, et al. "A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)." Leukemia, 2017;31(1):107-114. PMID: 27416912.
- [clinical-trial] Facon T, et al. "Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma." Blood, 2019;133(18):1953-1963. PMID: 30819926.
- [clinical-trial] Kumar SK, et al. "Carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma without intention for immediate autologous stem-cell transplantation (ENDURANCE): a multicentre, open-label, phase 3, randomised, controlled trial." Lancet Oncol, 2020;21(10):1317-1330. PMID: 32866432.
- [clinical-trial] Bringhen S, et al. "Carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial." Lancet Haematol, 2025;12(8):e621-e634. PMID: 40769686.
- [review] Waxman AJ, et al. "Carfilzomib-Associated Cardiovascular Adverse Events: A Systematic Review and Meta-analysis." JAMA Oncol, 2018;4(3):e174519. PMID: 29285538.
Sources & Citations
Studies were read from their PubMed abstracts; the label from DailyMed (Kyprolis, set ea66eb30, version 59, effective June 18, 2025), read October 28, 2026; approval records from Drugs@FDA and the EMA.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.