Kyprolis (Carfilzomib)
Proteasome Inhibitor for Relapsed or Refractory Multiple Myeloma
Quick Facts About Kyprolis
Key Takeaways About Kyprolis
- Hospital-administered treatment: Kyprolis is given as an intravenous infusion in a healthcare facility – it cannot be taken at home
- Combination therapy: Always used alongside other medicines (daratumumab + dexamethasone, lenalidomide + dexamethasone, or dexamethasone alone)
- Cardiovascular monitoring essential: Kyprolis can cause serious heart and lung problems, including heart failure and pulmonary hypertension – regular cardiac monitoring is required
- Hydration is critical: Patients must receive adequate intravenous or oral fluids before each infusion to protect the kidneys and reduce the risk of tumour lysis syndrome
- Cycle-based dosing: Treatment follows 28-day cycles with infusions on specific days (typically days 1, 2, 8, 9, 15, and 16), with dose calculated from body surface area
What Is Kyprolis and What Is It Used For?
Kyprolis (carfilzomib) is a proteasome inhibitor used to treat adult patients with multiple myeloma who have received at least one prior line of therapy. It works by irreversibly blocking the proteasome, a protein-degrading complex within cells, leading to accumulation of toxic misfolded proteins and ultimately cancer cell death.
Multiple myeloma is a cancer of the plasma cells, a type of white blood cell found in the bone marrow. Plasma cells normally produce antibodies (immunoglobulins) to help the body fight infections. In multiple myeloma, these cells become malignant and multiply uncontrollably, producing large quantities of abnormal antibodies while crowding out healthy blood cells. This can lead to bone destruction, anaemia, kidney damage, and increased susceptibility to infections.
Carfilzomib works by blocking the proteasome, a barrel-shaped protein complex found in all cells. The proteasome acts as a cellular recycling system that degrades damaged, misfolded, or unneeded proteins into smaller peptides. Cancer cells, particularly myeloma cells, produce large amounts of abnormal immunoglobulin proteins and rely heavily on the proteasome to dispose of them. By irreversibly binding to the chymotrypsin-like (beta-5) subunit of the 20S proteasome, carfilzomib causes these toxic proteins to accumulate inside the cancer cells. This triggers a cascade of cellular stress responses, including endoplasmic reticulum stress and activation of the unfolded protein response, which ultimately leads to apoptosis (programmed cell death).
A key distinction of carfilzomib compared to the first-generation proteasome inhibitor bortezomib is that carfilzomib binds irreversibly to the proteasome. This means that once it attaches, the enzyme is permanently inactivated and the cell must synthesise new proteasome molecules to restore function. In contrast, bortezomib binds reversibly. This irreversible mechanism contributes to carfilzomib's more potent and sustained proteasome inhibition, with greater than 80% inhibition of the chymotrypsin-like activity achieved at therapeutic doses.
Kyprolis is approved for use in combination with other medicines. The approved combinations include:
- Kyprolis + daratumumab + dexamethasone (KdD): Daratumumab is a monoclonal antibody targeting CD38 on myeloma cells. This triplet combination has demonstrated significant improvements in progression-free survival in the CANDOR trial.
- Kyprolis + lenalidomide + dexamethasone (KRd): Lenalidomide is an immunomodulatory drug. The ASPIRE trial demonstrated a median progression-free survival benefit of 26.3 months versus 17.6 months with lenalidomide and dexamethasone alone.
- Kyprolis + dexamethasone (Kd): For patients who cannot receive lenalidomide or daratumumab, this two-drug combination provides an effective alternative, as demonstrated in the ENDEAVOR trial.
Kyprolis was first approved by the U.S. Food and Drug Administration (FDA) in 2012 and by the European Medicines Agency (EMA) in 2015. It is manufactured by Amgen and is available worldwide for the treatment of relapsed or refractory multiple myeloma. The World Health Organization recognises proteasome inhibitors as a cornerstone of modern myeloma treatment, significantly improving survival outcomes compared to older chemotherapy regimens.
What Should You Know Before Receiving Kyprolis?
Before starting Kyprolis, your doctor will perform a thorough medical evaluation including blood tests and cardiac assessment. You should not receive Kyprolis if you are allergic to carfilzomib. Inform your doctor about any heart, lung, kidney, or liver conditions, bleeding disorders, or current medications.
Your doctor will review your complete medical history and conduct blood tests before starting treatment with Kyprolis. These tests check that your blood cell counts are adequate and that your liver and kidneys are functioning properly. You will continue to have blood tests throughout treatment to monitor for potential side effects. Your healthcare team will also ensure that you are properly hydrated before each infusion.
Contraindications
You should not receive Kyprolis if:
- You are allergic to carfilzomib or any of the other ingredients in this medicine (listed in the Ingredients section below)
Because Kyprolis is given in combination with other medicines, you must also read the patient information for those medicines. For example, lenalidomide is strictly contraindicated in pregnancy and requires adherence to a pregnancy prevention programme.
Warnings and Precautions
Talk to your doctor or nurse before receiving Kyprolis if you have or have had any of the following conditions, as you may need additional monitoring:
- Heart problems: Previous chest pain (angina), heart attack, heart failure, irregular heartbeat, high blood pressure, or if you have ever taken heart medications. Kyprolis can cause serious cardiovascular events including cardiac failure, cardiac arrest, and myocardial ischaemia.
- Lung problems: Shortness of breath at rest or during activity (dyspnoea). Kyprolis can cause pulmonary toxicity, pulmonary hypertension, and acute respiratory distress syndrome.
- Kidney problems: Renal impairment or a history of dialysis. Kyprolis can worsen kidney function and cause acute kidney injury, particularly in the setting of tumour lysis syndrome.
- Liver problems: Previous hepatitis, fatty liver disease, or known liver dysfunction. Kyprolis can cause hepatic toxicity, elevated liver enzymes, and in rare cases, liver failure.
- Bleeding disorders: Unusual bruising, prolonged bleeding from cuts, or a history of internal bleeding. Kyprolis can cause thrombocytopenia (low platelet count) which increases bleeding risk.
- Blood clots: A history of deep vein thrombosis or pulmonary embolism. Thrombotic events including deep venous thrombosis and pulmonary embolism have been reported during Kyprolis treatment.
- Hepatitis B infection: Tell your doctor if you have ever had hepatitis B, as Kyprolis may cause reactivation of the virus. Your doctor will test for hepatitis B before, during, and for some time after treatment.
- Chest pain, shortness of breath, or swollen feet (possible heart problems)
- Difficulty breathing, wheezing, or rapid breathing at rest (possible lung problems)
- Reduced urine output, swollen ankles, or abnormal blood test results (possible kidney problems)
- Yellowing of the skin or eyes, dark urine, or abdominal swelling (possible liver problems)
- Fever, chills, facial swelling, difficulty swallowing, or a feeling of tightness in the chest (possible infusion reaction)
- Unusual bleeding or bruising, blood in sputum or stool, or sudden severe headache (possible bleeding or low platelets)
- Headache, confusion, seizures, or vision loss (possible PRES – posterior reversible encephalopathy syndrome)
Pregnancy and Breastfeeding
For women receiving Kyprolis: Do not use Kyprolis if you are pregnant, think you may be pregnant, or are planning to become pregnant. The effects of Kyprolis on the unborn child have not been studied in humans. You must use effective contraception during treatment and for 30 days after the last dose. If you become pregnant during treatment, inform your doctor immediately.
Do not breastfeed while receiving Kyprolis. It is not known whether carfilzomib passes into breast milk, and a risk to the nursing infant cannot be excluded.
For men receiving Kyprolis: You must use condoms during treatment and for 90 days after the last dose, even if your partner is pregnant. If your partner becomes pregnant during this time, inform your doctor immediately.
If Kyprolis is given in combination with lenalidomide, you must follow the strict pregnancy prevention programme for lenalidomide, as this drug is known to cause severe birth defects. Your doctor will provide detailed information about contraception requirements.
Driving and Operating Machinery
Kyprolis may cause fatigue, dizziness, fainting, and low blood pressure. If you experience any of these symptoms, do not drive or operate machinery until the effects have resolved. Discuss with your healthcare team when it is safe to resume driving.
Sodium and Excipient Information
Kyprolis contains sodium. This medicine contains 37 mg sodium per 10 mg vial (1.9% of WHO recommended maximum daily intake), 109 mg per 30 mg vial (5.5%), or 216 mg per 60 mg vial (11%). This should be taken into consideration for patients on a sodium-restricted diet. Kyprolis also contains sulfobutylbetadex sodium (a cyclodextrin), which is used as a solubiliser.
How Does Kyprolis Interact with Other Drugs?
Carfilzomib has a limited drug interaction profile compared to some other anticancer agents, as it is primarily metabolised by peptidase cleavage and epoxide hydrolysis rather than cytochrome P450 enzymes. However, important interactions exist with combination partners and certain other medications. Always inform your doctor about all medicines you are taking.
Unlike many small-molecule drugs, carfilzomib is a tetrapeptide that is predominantly metabolised by peptidase activity and epoxide hydrolysis, not by cytochrome P450 (CYP) enzymes. In vitro studies have shown that carfilzomib is a minor substrate of CYP3A4 and does not significantly inhibit or induce major CYP enzymes at clinically relevant concentrations. This means that carfilzomib has a relatively low potential for pharmacokinetic drug-drug interactions. However, several clinically important interactions and precautions remain.
Combination Partner Interactions
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Lenalidomide | Immunomodulatory agent | Used in combination; both are myelosuppressive. Increased risk of thrombocytopenia, neutropenia, and thrombotic events | Monitor blood counts closely. Thromboprophylaxis recommended |
| Dexamethasone | Corticosteroid | Used in all approved combinations. Dexamethasone is a strong CYP3A4 inducer, but this does not significantly affect carfilzomib levels | Follow prescribed combination regimen. Monitor blood glucose and infection risk |
| Daratumumab | Anti-CD38 monoclonal antibody | No pharmacokinetic interaction. Additive myelosuppression. Increased infusion reaction risk | Pre-medication for infusion reactions. Monitor blood counts |
Other Important Interactions
| Drug | Category | Effect | Recommendation |
|---|---|---|---|
| Hormonal contraceptives | Contraception | Oral contraceptives may have reduced effectiveness due to combination therapy effects (especially dexamethasone) | Use barrier methods or non-hormonal contraception during treatment |
| Strong CYP3A4 inhibitors (ketoconazole, ritonavir) | Antifungals / antivirals | May slightly increase carfilzomib exposure, though carfilzomib is a minor CYP3A4 substrate | Use with caution; monitor for increased toxicity |
| Strong CYP3A4 inducers (rifampicin, phenytoin) | Antibiotics / anticonvulsants | May slightly reduce carfilzomib exposure | Consider potential for reduced efficacy; consult oncologist |
| Anticoagulants (warfarin, heparin) | Blood thinners | Kyprolis can cause thrombocytopenia, increasing bleeding risk when combined with anticoagulants | Monitor platelet counts and coagulation parameters closely |
| Vaccines (live) | Immunisations | Immunosuppressed patients may have inadequate vaccine response; risk of vaccine-strain infection with live vaccines | Avoid live vaccines during treatment. Inactivated vaccines may be used with reduced efficacy |
Because Kyprolis is always administered in a hospital or clinic setting by healthcare professionals, all drug interactions are managed within the clinical care context. You should provide your treating oncologist with a complete list of all medications, supplements, and herbal products you are taking, including over-the-counter medicines and vitamins. This helps your medical team identify and manage any potential interactions throughout your treatment.
What Is the Correct Dosage of Kyprolis?
Kyprolis is given as an intravenous infusion by a doctor or nurse. The dose is calculated based on your body surface area (height and weight). Treatment follows 28-day cycles, with infusions on specific days within each cycle. Your oncologist will determine the exact dose and schedule based on the combination regimen being used.
Kyprolis is always administered by a healthcare professional in a hospital or clinic. You cannot self-administer this medicine. The dose is individually calculated based on your body surface area (BSA), which is derived from your height and weight at the start of treatment. Patients with a BSA greater than 2.2 m² receive a dose based on a maximum BSA of 2.2 m². Dose adjustments for weight changes of 20% or less are not required.
Treatment Schedule
Each treatment cycle lasts 28 days. Within each cycle, Kyprolis is typically administered on days 1, 2, 8, 9, 15, and 16, followed by a 12-day rest period. The infusion is given over approximately 10 to 30 minutes depending on the dose. The specific dosing schedule varies by combination regimen.
Kyprolis + Lenalidomide + Dexamethasone (KRd)
Cycle 1: 20 mg/m² on days 1 and 2, then 27 mg/m² on days 8, 9, 15, and 16
Cycles 2–12: 27 mg/m² on days 1, 2, 8, 9, 15, and 16
Cycles 13 onwards: 27 mg/m² on days 1, 2, 15, and 16 (days 8 and 9 are omitted)
Infusion duration: 10 minutes
Kyprolis + Dexamethasone (Kd)
Cycle 1: 20 mg/m² on days 1 and 2, then 56 mg/m² on days 8, 9, 15, and 16
Cycles 2 onwards: 56 mg/m² on days 1, 2, 8, 9, 15, and 16
Infusion duration: 30 minutes
Kyprolis + Daratumumab + Dexamethasone (KdD)
Cycle 1: 20 mg/m² on days 1 and 2, then 56 mg/m² on days 8, 9, 15, and 16
Cycles 2 onwards: 56 mg/m² on days 1, 2, 8, 9, 15, and 16
Infusion duration: 30 minutes
Hydration Requirements
Adequate hydration is essential before and during Kyprolis treatment to reduce the risk of kidney damage and tumour lysis syndrome. Your healthcare team will ensure you receive sufficient intravenous or oral fluids before each infusion, particularly during the first cycle and at dose escalation. Blood tests will be performed to monitor kidney function and electrolytes throughout treatment.
Dose Modifications
Your doctor may reduce your dose, delay treatment, or stop Kyprolis temporarily or permanently if you develop significant side effects. Dose modifications are based on the type and severity of the adverse effect. Common reasons for dose adjustment include:
- Haematological toxicity (low blood cell counts, particularly neutropenia and thrombocytopenia)
- Cardiac toxicity (heart failure, reduced heart function)
- Pulmonary toxicity (lung complications)
- Renal toxicity (kidney problems)
- Hepatic toxicity (liver problems)
- Peripheral neuropathy (nerve damage)
Treatment Duration
Most patients continue Kyprolis treatment for as long as the disease improves or remains stable and the side effects are manageable. Your oncologist will regularly assess your response to treatment through blood tests and potentially bone marrow biopsies. Treatment may also be stopped if side effects become too severe to control with dose adjustments.
Overdose
Because Kyprolis is administered by healthcare professionals in a clinical setting, overdose is unlikely. However, if an overdose were to occur, there is no specific antidote. The patient would be monitored for side effects and given supportive treatment as needed. If you have any concerns about the dose you have received, speak to your doctor or nurse immediately.
What Are the Side Effects of Kyprolis?
Kyprolis can cause a wide range of side effects. Very common side effects include pneumonia, low blood cell counts, fatigue, diarrhoea, nausea, high blood pressure, and shortness of breath. Some side effects can be serious or life-threatening, particularly cardiovascular events, lung problems, kidney failure, and tumour lysis syndrome. Your medical team will monitor you closely throughout treatment.
Like all medicines, Kyprolis can cause side effects, although not everybody gets them. Because Kyprolis is used to treat cancer and is a potent drug, side effects are common and can sometimes be serious. Your healthcare team is experienced in managing these effects and will monitor you with regular blood tests and clinical assessments.
- Heart problems: Chest pain, shortness of breath, swollen feet, irregular heartbeat, rapid pulse
- Lung problems: Difficulty breathing at rest or during activity, wheezing, cough, feeling that you cannot get enough air
- Hypertensive crisis: Very high blood pressure with severe headache, confusion, blurred vision, nausea
- Kidney problems: Reduced urine output, swelling, abnormal blood test results
- Tumour lysis syndrome: Irregular heartbeat, kidney failure, or abnormal blood tests caused by rapid breakdown of cancer cells
- Infusion reactions: Fever, chills, facial flushing, facial or throat swelling, difficulty breathing, low blood pressure
- Bleeding: Unusual bruising, blood in cough, vomit, or stool, sudden severe headache
- Blood clots: Pain or swelling in legs or arms, chest pain, sudden shortness of breath
- Liver problems: Yellowing of skin or eyes, abdominal pain or swelling, nausea, vomiting
- PRES: Headache, confusion, seizures, vision loss, high blood pressure
Very Common
May affect more than 1 in 10 people
- Pneumonia (serious lung infection)
- Upper respiratory tract infections
- Thrombocytopenia (low platelets – may cause bruising or bleeding)
- Neutropenia (low white blood cells – increased infection risk)
- Anaemia (low red blood cells – causing tiredness)
- Decreased appetite
- Low potassium levels, elevated creatinine
- Insomnia (difficulty sleeping)
- Headache
- Peripheral neuropathy (numbness, tingling in hands/feet)
- Dizziness
- Hypertension (high blood pressure)
- Dyspnoea (shortness of breath)
- Cough
- Diarrhoea
- Nausea
- Constipation
- Vomiting
- Abdominal pain
- Back pain, joint pain
- Pain in extremities, muscle spasms
- Fever, chills
- Oedema (swelling of hands, feet, or ankles)
- Fatigue (tiredness), weakness
Common
May affect up to 1 in 10 people
- Infusion reactions
- Heart failure and cardiac events, including rapid or irregular heartbeat
- Heart attack (myocardial infarction)
- Kidney problems, including kidney failure
- Deep vein thrombosis (blood clots in veins)
- Pulmonary embolism (blood clots in lungs)
- Fluid in the lungs, wheezing
- Sepsis (severe bloodstream infection)
- Liver problems (elevated liver enzymes)
- Influenza-like symptoms
- Herpes zoster (shingles) reactivation
- Urinary tract infection
- Bronchitis, sore throat, rhinitis
- Gastrointestinal bleeding
- Dehydration, anxiety, confusion
- Blurred vision, cataracts
- Low blood pressure (hypotension)
- Nosebleeds, hoarseness
- Skin rash, itching, increased sweating
- Bone pain, muscle weakness, chest pain
- Injection site reactions
- Tinnitus (ringing in ears)
Uncommon
May affect up to 1 in 100 people
- Pulmonary haemorrhage (bleeding in the lungs)
- Clostridium difficile colitis (severe intestinal infection)
- Allergic reactions to Kyprolis
- Multi-organ failure
- Reduced blood flow to the heart (myocardial ischaemia)
- Cerebral haemorrhage (brain bleeding)
- Stroke
- Acute respiratory distress syndrome
- Pericarditis (inflammation of the heart sac)
- Pericardial effusion (fluid around the heart)
- Cholestasis (blockage of bile flow from liver)
- Gastrointestinal perforation
- Cytomegalovirus infection
- Hepatitis B reactivation
- Pancreatitis (inflammation of the pancreas)
- Thrombotic microangiopathy
- Posterior reversible encephalopathy syndrome (PRES)
If you notice any side effects not listed here, or if any side effect becomes severe, tell your doctor or nurse. Reporting suspected side effects helps ongoing monitoring of the medicine's benefit-risk balance. You can report side effects to your national medicines regulatory authority.
How Should Kyprolis Be Stored?
Kyprolis is stored by your pharmacy or hospital pharmacy under specific conditions. Unopened vials must be refrigerated at 2–8°C (36–46°F), protected from light, and must not be frozen. The reconstituted solution should be used immediately or within 24 hours if refrigerated.
As a hospital-administered medicine, Kyprolis is stored and handled by trained pharmacy and nursing staff. You do not need to store this medicine at home. However, for general information:
- Unopened vials: Store in a refrigerator at 2–8°C (36–46°F). Do not freeze. Keep in the original packaging to protect from light.
- After reconstitution: The reconstituted solution should be a clear, colourless to slightly yellow liquid. It should not be administered if any discolouration or particles are observed.
- Stability: The reconstituted solution should be used immediately. If not used immediately, it may be stored for up to 24 hours at 2–8°C.
- Single-use only: Each vial is intended for single use. Any unused medicine must be discarded according to local requirements for handling cytotoxic waste.
Do not use this medicine after the expiry date stated on the vial and carton. The expiry date refers to the last day of the stated month. Keep all medicines out of the sight and reach of children.
What Does Kyprolis Contain?
Each vial of Kyprolis contains carfilzomib as the active ingredient, along with sulfobutylbetadex sodium (cyclodextrin) as a solubiliser, anhydrous citric acid, and sodium hydroxide. After reconstitution, the solution contains 2 mg/mL of carfilzomib.
Active Ingredient
The active substance is carfilzomib. Kyprolis is available in three vial sizes:
- 10 mg vial: Contains 10 mg carfilzomib
- 30 mg vial: Contains 30 mg carfilzomib
- 60 mg vial: Contains 60 mg carfilzomib
After reconstitution with sterile water for injection, each millilitre of solution contains 2 mg carfilzomib.
Inactive Ingredients (Excipients)
The other ingredients are:
- Sulfobutylbetadex sodium (betadex sulfobutyl ether sodium) – a cyclodextrin used to improve the solubility of carfilzomib
- Anhydrous citric acid (E330) – a pH-adjusting agent
- Sodium hydroxide – used for pH adjustment
Appearance and Packaging
Kyprolis is supplied as a white to off-white powder (lyophilised cake) in a glass vial with a rubber stopper. Before administration, the powder is reconstituted with sterile water for injection to produce a clear, colourless to slightly yellow solution. Each carton contains one vial.
Sodium Content
This medicine contains sodium:
- 10 mg vial: 37 mg sodium (1.9% of WHO recommended maximum daily intake of 2 g)
- 30 mg vial: 109 mg sodium (5.5% of WHO recommended maximum daily intake)
- 60 mg vial: 216 mg sodium (11% of WHO recommended maximum daily intake)
Patients on a sodium-restricted diet should be aware of this content, particularly those receiving higher doses or multiple vials per treatment day.
How Does Kyprolis Work in the Body?
Kyprolis works by irreversibly inhibiting the proteasome, a protein-degrading complex essential for cellular function. By blocking the proteasome, carfilzomib causes toxic accumulation of misfolded and ubiquitinated proteins in myeloma cells, triggering endoplasmic reticulum stress and ultimately apoptosis (programmed cell death). Myeloma cells are particularly susceptible due to their high rate of protein production.
The ubiquitin-proteasome pathway is one of the most important protein degradation systems in human cells. Proteins that are damaged, misfolded, or no longer needed are tagged with ubiquitin molecules and then delivered to the proteasome for degradation. The 26S proteasome consists of a 20S core particle (the catalytic barrel) flanked by two 19S regulatory caps. The 20S core contains three distinct catalytic sites: chymotrypsin-like (beta-5), trypsin-like (beta-2), and caspase-like (beta-1).
Carfilzomib is a tetrapeptide epoxyketone that selectively and irreversibly binds to the chymotrypsin-like (beta-5) subunit of the 20S proteasome. The epoxyketone warhead forms a dual covalent bond with the N-terminal threonine of the active site, resulting in permanent enzyme inactivation. This is in contrast to bortezomib, which contains a boronic acid warhead that forms a reversible bond. The irreversible nature of carfilzomib's binding means that proteasome activity can only be restored through de novo synthesis of new proteasome subunits, which provides more sustained inhibition.
Myeloma cells are uniquely vulnerable to proteasome inhibition because they are highly active secretory cells that produce vast quantities of monoclonal immunoglobulins. This places an enormous burden on the proteasome system for protein quality control. When the proteasome is inhibited, these cells rapidly accumulate misfolded proteins, leading to overwhelming endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is activated but cannot cope with the protein overload, ultimately activating pro-apoptotic signalling pathways and triggering cell death.
Pharmacokinetic Profile
Carfilzomib is administered intravenously and is rapidly and extensively metabolised. Its plasma half-life is approximately 1 hour, and clearance is primarily through peptidase cleavage and epoxide hydrolysis rather than hepatic CYP-mediated metabolism. Despite the short plasma half-life, the pharmacodynamic effect is prolonged because carfilzomib binds irreversibly to the proteasome. Proteasome recovery requires synthesis of new proteasome subunits, which takes approximately 48 hours or longer.
At therapeutic doses, carfilzomib achieves greater than 80% inhibition of the chymotrypsin-like activity of the proteasome in peripheral blood mononuclear cells and in tumour tissue. The degree of proteasome inhibition correlates with both dose and clinical efficacy. Carfilzomib does not significantly accumulate with repeated dosing, and its pharmacokinetics are linear across the clinical dose range.
Frequently Asked Questions About Kyprolis
Kyprolis (carfilzomib) is used to treat adult patients with multiple myeloma, a cancer of plasma cells in the bone marrow. It is specifically approved for patients who have already received at least one prior line of therapy. Kyprolis is always used in combination with other medicines – either daratumumab and dexamethasone, lenalidomide and dexamethasone, or dexamethasone alone. It works by blocking the proteasome, leading to the death of cancer cells.
The most serious side effects of Kyprolis include cardiovascular events (heart failure, heart attack, pulmonary hypertension), acute kidney injury, tumour lysis syndrome, pulmonary toxicity (including acute respiratory distress syndrome), thrombotic microangiopathy, hepatic toxicity, posterior reversible encephalopathy syndrome (PRES), and severe infusion reactions. Your healthcare team will monitor you closely with blood tests and clinical assessments to detect these early.
No, Kyprolis must be administered by a healthcare professional in a hospital or clinic setting. It is given as an intravenous infusion over 10 to 30 minutes and requires reconstitution by trained pharmacy staff using aseptic technique. Your vital signs and hydration status are monitored during and after the infusion. You cannot self-administer this medicine at home.
Adequate hydration is essential before Kyprolis infusions to protect your kidneys and reduce the risk of tumour lysis syndrome. When cancer cells are killed rapidly by Kyprolis, they release their contents (potassium, phosphate, uric acid) into the bloodstream, which can overwhelm the kidneys. Proper hydration helps the kidneys flush these substances out. Your healthcare team will give you intravenous or oral fluids before and after each infusion and monitor your kidney function with blood tests.
The duration of Kyprolis treatment varies from patient to patient. Treatment continues for as long as the disease responds to therapy or remains stable, and as long as the side effects are manageable. Some patients may receive treatment for many months or even years. Your oncologist will regularly assess your response through blood tests, imaging, and potentially bone marrow biopsies to determine whether to continue treatment.
No, although both are proteasome inhibitors used to treat multiple myeloma, they are different drugs. Kyprolis (carfilzomib) is a second-generation proteasome inhibitor that binds irreversibly to the proteasome, whereas bortezomib (Velcade) is a first-generation proteasome inhibitor that binds reversibly. Kyprolis was specifically designed to provide more potent and sustained proteasome inhibition with a different side effect profile. Notably, carfilzomib has a lower incidence of peripheral neuropathy compared to bortezomib but carries a higher risk of cardiovascular side effects.
References
- Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372(2):142-152. doi:10.1056/NEJMoa1411321 (ASPIRE trial)
- Dimopoulos MA, Moreau P, Palumbo A, 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.
- Usmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022;23(1):65-76.
- European Medicines Agency. Kyprolis (carfilzomib) – Summary of Product Characteristics. Available at: ema.europa.eu (accessed December 2025).
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 5.2025.
- Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines. Ann Oncol. 2021;32(3):309-322.
- World Health Organization. WHO Model List of Essential Medicines – 23rd list, 2023.
- U.S. Food and Drug Administration. Kyprolis (carfilzomib) prescribing information. Revised 2024.
About Our Medical Team
This article was written and reviewed by iMedic's medical editorial team, which includes board-certified specialists in oncology, haematology, and clinical pharmacology. Our team follows international guidelines from the European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN), and the World Health Organization (WHO).
iMedic Medical Editorial Team – Specialists in oncology and clinical pharmacology with documented academic backgrounds and clinical experience in haematological malignancies.
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