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Kyprolis: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on May 23, 2022.

1. How it works

  • Kyprolis is a brand (trade) name for carfilzomib, a chemotherapy agent that may be used to treat multiple myeloma.
  • Kyprolis works by inhibiting proteasomes - these are a group of enzymes that break down proteins in the body. Proteasomes work via the ubiquitin-proteasome pathway (UPP) to break down or degrade many cellular proteins. Research has found that defects within the UPP are associated with the development of multiple myeloma and treatment with Kyprolis causes an accumulation of misfolded monoclonal immunoglobulins (Ig) in plasma cells. This stresses the cells and results in the activation of the unfolded protein response (UPR) pathway which stops the usual cell cycle process and induces cell death (also called apoptosis). Multiple myeloma plasma cells with high Ig production are preferentially targeted.
  • Kyprolis belongs to the class of medicines known as proteasome inhibitors. It may also be called a second-generation proteasome inhibitor.

2. Upsides

  • May be used to treat relapsed or refractory multiple myeloma in adults who have received 1 to 3 lines of therapy. Used in combination with either lenalidomide and dexamethasone; dexamethasone; or daratumumab and dexamethasone.
  • May be given as a single agent in adults with relapsed or refractory multiple myeloma who have received 1 or more lines of treatment.
  • Kyprolis is given directly into a vein and the IV infusion takes from 10 to 30 minutes (depending on what it is given with).
  • Pre-treatment with dexamethasone reduces the incidence and severity of infusion-related adverse reactions.
  • Inhibits the growth of cells and causes cells to self-destruct.
  • Dose changes are not necessary for weight changes of 20% or less.
  • The injection contains no preservative and is for single-use only.
  • Available as a 10mg, 30mg, or 60mg vial.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Fatigue, shortness of breath, fever, low platelets (thrombocytopenia), nausea, anemia, high blood pressure, chills, headache, cough, vomiting, insomnia, are common side effects of Kyprolis. Diarrhea, lymphopenia, edema, chest or back pain, decreased appetite, muscle spasms, cough, blood creatinine increase, and upper respiratory tract infections have also been reported. A large number of other side effects have occurred at an incidence of less than 10%.
  • Shortness of breath (dyspnea) has been reported in 25% of people treated with Kyprolis. Less than 1% reported Grade 3 or greater. Stop Kyprolis for Grade 3 or 4 dyspnea until it has resolved.
  • Laboratory abnormalities may include decreased lymphocytes, platelets, hemoglobin, total white blood cell count, sodium, phosphorous, creatinine clearance, or absolute neutrophils and increased potassium and uric acid.
  • Fatal and serious cases of hemorrhage have been reported.
  • Kyprolis causes thrombocytopenia (reported in approximately 32% of those in clinical trials); platelet nadirs are usually observed between Day 8 and Day 15 of each 28-day cycle. Monitor platelet counts and consider reducing or withholding a dose of Kyprolis if they are too low.
  • Can cause infusion-related reactions; some may be life-threatening. Symptoms include fever, chills, joint or muscle pain, facial flushing, edema, vomiting, weakness, chest tightness, or angina. These reactions can occur up to 24 hours after administration of Kyprolis. Administering dexamethasone before Kyprolis reduces the incidence of these reactions.
  • Cardiac toxicities, acute renal failure, liver failure, pulmonary toxicity, pulmonary hypertension, high blood pressure, tumor lysis syndrome, posterior reversible encephalopathy syndrome (PRES), venous thrombosis, TTP/HUS (thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome), have been reported in patients receiving Kyprolis. Some of these events have been fatal. Optimize blood pressure before starting Kyprolis and monitor BP regularly.
  • Given by intravenous (IV) infusion and needs to be administered by a health professional in a clinic, hospital, or doctor’s office. Either given on two consecutive days each week or once a week, depending on what it is given with. A standard Kyprolis treatment cycle involves receiving infusions for three consecutive weeks, followed by one week off of treatment.
  • Patients must be adequately hydrated before dosing in Cycle 1, especially patients at high risk of tumor lysis syndrome (TLS) or kidney toxicity. Consider hydration with both oral fluids (30mL per kg at least 48 hours before Cycle 1) and IV fluids (250mL to 500mL before each dose in Cycle 1). Monitor patients for evidence of overhydration particularly those with heart failure and adjust the level of hydration as needed.
  • Monitor serum potassium levels regularly during treatment.
  • Provide thromboprophylaxis to reduce the risk of deep vein thrombosis or pulmonary embolism in those patients receiving Kyprolis in combination with lenalidomide and dexamethasone.
  • In those patients at risk of herpes reactivation, administer antiviral medications before Kyprolis treatment.
  • Administer Kyprolis after hemodialysis in those patients who receive it.
  • For people with a body surface area of 2.2m2 or less, calculate the dose of Kyprolis using actual BSA.
  • The dosage of Kyprolis may need to be withheld or modified if the following occur: absolute neutrophil count (ANC) <0.5 x 109/L, ANC plus oral temperature >38.5°C or two consecutive readings of more than 38.0°C for 2 hours; platelets <10 x 109/L or evidence of bleeding with thrombocytopenia; severe or life-threatening non-hematological toxicities; hepatic impairment, or renal toxicity.
  • Conduct a pregnancy test before initiating Kyprolis. Advise females of reproductive potential to use effective contraception during treatment with Kyprolis and for 6 months following the final dose. Kyprolis can cause fetal harm to the unborn baby. Advise males with female partners of reproductive potential to use effective contraception during treatment with Kyprolis and for 3 months following the final dose. Women should not breastfeed while being treated with Kyprolis and for 2 weeks following the final dose. May affect fertility.
  • The safety of Kyprolis in children has not been established. The incidence of side effects appears to increase with age (incidence < 49% in patients less than 65 years increases to >63% in those older than 75).

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Kyprolis is a chemotherapy agent that may be used to treat multiple myeloma. It is given by infusion either alone or in combination with other medications once or twice weekly by a healthcare professional. Side effects are common and may include fatigue, shortness of breath, fever, or laboratory abnormalities such as thrombocytopenia, decreased lymphocytes, and lower hemoglobin. Serious side effects of Kyprolis include cardiac toxicities, infusion-related reactions, and hemorrhage.

5. Tips

  • Your oncologist will advise you how often you will receive Kyprolis and if you will receive it in combination with other medications, such as dexamethasone, lenalidomide, or daratumumab, or by itself.
  • Keep your scheduled appointments as Kyprolis needs to be administered by a health professional in a clinic, hospital, or doctor’s office. It is usually either given on two consecutive days each week or once a week, depending on what it is given with. A standard Kyprolis treatment cycle involves receiving infusions for three consecutive weeks, followed by one week off of treatment.
  • Kyprolis commonly causes reactions around the site of the infusion. Some may be life-threatening. Symptoms include fever, chills, joint or muscle pain, facial flushing, fluid retention, vomiting, weakness, chest tightness, or angina. These reactions can occur up to 24 hours after administration of Kyprolis. Administering dexamethasone before Kyprolis reduces the incidence of these reactions. Tell your doctor if you experience any reaction.
  • Tell your doctor immediately if you become short of breath (commonly develops within a day of receiving Kyprolis); develop chest pain, or severe calf or leg pain (may be a symptom of a blood clot); experience pain in your stomach, fatigue, or yellow discoloration of your skin or eyes; or neurological symptoms such as confusion, dizziness, or headache; problems with balance; weakness down one side of your body; seizures; or visual loss.
  • Avoid becoming dehydrated while receiving Kyprolis. It is particularly important to keep your fluid intake high if you develop vomiting or diarrhea because both these conditions can rapidly dehydrate you. If you experience symptoms of dehydration, such as extreme thirst; dry mouth, lips, or eyes; rapid weight loss; tiredness; or headache, contact your doctor immediately.
  • Kyprolis may make you bruise or bleed more easily, and it may take longer to stop the bleeding. Seek urgent attention for any prolonged, unusual, or excessive bleeding, and if you develop black, tarry, stools or see blood in your bowel motions.
  • Kyprolis may make you drowsy and affect your ability to drive or operate machinery. Do not perform hazardous tasks if Kyprolis affects you like this.
  • Tell your doctor about any medication that you take, whether prescribed or brought over the counter because some medications may not be compatible with Kyprolis.
  • Use effective contraception while being administered Kyprolis and for 6 months after the last dose if you are a female with reproductive potential. Female partners of males being administered Kyprolis should also use effective contraceptive while their male partner is on Kyprolis and for 3 months after his last dose. If you inadvertently become pregnant while being exposed to Kyprolis, tell your doctor immediately. Do not breastfeed while being treated with Kyprolis and for 2 weeks following the final dose.

6. Response and effectiveness

  • The ASPIRE trial compared Kyprolis with lenalidomide plus dexamethasone (KRd) to lenalidomide and dexamethasone (Rd) alone reported a median progression-free survival (PFS) of 26.3 months with KRd compared to 17.6 months with Rd. Overall survival was 48.3 months with KRd compared to 40.4 months with Rd. The median duration of response was 28.6 months for those in the KRd arm and 21.1 months for those in the Rd arm.
  • The ENDEAVOR randomized, open-label trial compared Kyprolis plus dexamethasone (Kd) to bortezomib plus dexamethasone (Vd). A PFS of 18.7 months for Kd versus 9.4 months for Vd was reported. Overall survival was 47.6 months in the Kd arm versus 40 months in the Vd arm.
  • The ARROW randomized, open-label trial compared Kd once weekly to Kd twice weekly. The initial dosage was 20 mg/m2 which was increased to 70 mg/m2. PFS and overall survival were significantly better in the once-weekly arm.
  • Other trials have investigated Kyprolis in combination with other treatments, such as daratumumab, or as monotherapy with mostly positive results.

7. Interactions

Medicines that interact with Kyprolis may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Kyprolis. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Kyprolis interacts with over 270 medications; the majority of these interactions are considered major or moderate. Common medications that may interact with Kyprolis include:

  • aminocaproic acid
  • antipsychotics such as clozapine
  • other biologics, such as adalimumab, etanercept, golimumab, or infliximab
  • C1 esterase inhibitors
  • chloroquine or hydroxychloroquine
  • coagulation factor IX, VIIa, or X
  • conjugated estrogens and other estrogens, such as estradiol
  • danazol
  • deferiprone
  • digoxin
  • etanercept
  • fibrinogen
  • fingolimod
  • heart medications, such as amiodarone
  • herbals, such as black cohosh or brewer's yeast
  • HIV medications such as efavirenz or zidovudine
  • hydralazine
  • immunosuppressants such as azathioprine
  • infliximab
  • interferon or peginterferon
  • live vaccines and some other vaccines, such as BCG, cholera, Sars-COV-2 (covid-19) vaccines, measles, hepatitis b vaccines, yellow fever, or live or inactivated influenza vaccines
  • methotrexate
  • metronidazole
  • ozanimod
  • paclitaxel
  • probiotics, such as lactobacillus
  • progestins, such as levonorgestrel or norgestrel
  • raloxifene
  • siponimod
  • statins, such as atorvastatin
  • tamoxifen
  • testosterone
  • tranexamic acid
  • von willebrand factor.

Fatal and serious toxicities have been reported when Kyprolis is used in combination with melphalan and prednisone in newly diagnosed transplant-ineligible patients. Avoid the combination.

Note that this list is not all-inclusive and includes only common medications that may interact with Kyprolis. You should refer to the prescribing information for Kyprolis for a complete list of interactions.

References

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Kyprolis only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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