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KYPROLIS® (carfilzomib) is the second agent in a drug class called proteasome inhibitors approved by the U.S. Food and Drug Administration (FDA) in 2012 for the treatment of myeloma. 

What Are the Indications for Treatment with Kyprolis? 

Kyprolis is approved by the FDA in the following settings: 

  • Kyprolis in combination with the steroid dexamethasone [Kd] for the treatment of patients with relapsed or refractory myeloma  who have received 1 to 3 prior lines of therapy. 
  • Kyprolis as a single agent for the treatment of patients with relapsed or refractory myeloma who have received 1 or more prior lines of therapy. 
  • Kyprolis in combination with immunomodulatory agent Revlimid® (lenalidomide) plus dexamethasone [KRd] for the treatment of patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy. 
  • Kyprolis in combination with monoclonal antibody Darzalex® (daratumumab) or Darzalex Faspro® (daratumumab plus hyaluronidase- fihj) plus dexamethasone for the treatment of patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy. 
  • Kyprolis in combination with monoclonal antibody Sarclisa® (isatuximab-irfc) plus dexamethasone [Isa-Kd] for patients with relapsed or refractory myeloma who have received 1 to 3 prior lines of therapy. 

How Does Kyprolis Work?

Kyprolis works by blocking the activity of enzyme complexes called proteasomes.  

Both normal cells and cancer cells contain proteasomes. These proteasomes break down damaged and unwanted proteins into smaller components.  

Proteasomes also carry out the regulated breakdown of undamaged proteins in the cell. This process is necessary for the control of many critical cellular functions. Then, these smaller protein components create new proteins required by the cell.  

This is important for maintaining balance within the cell and for regulating cell growth.  

Kyprolis forms an irreversible bond with the proteasomes in myeloma cells. Those myeloma cells stop dividing and undergo apoptosis, a cellular process leading to the death of a cell.  

The myeloma cells also stop producing chemicals to stimulate other cancer cells.  

Myeloma cells are more sensitive to proteasome inhibition than normal cells. That’s why the myeloma cells die while normal cells can recover. 

How Is Kyprolis Given?

Kyprolis is a freeze-dried (lyophilized) powder that must be reconstituted (dissolved) before it is given by intravenous (IV) infusion at a doctor’s office, hospital, or clinic. At the treating physician's discretion, hydration may be given before and after each dose of Kyprolis. This step will be based upon the following: 

  • the patient’s tolerance of Kyprolis 
  • the dose of Kyprolis 
  • the duration of infusion time. 

Caution must be exercised to avoid fluid overload. 

In patients with mild or moderate hepatic (liver) impairment, the dose of Kyprolis must be reduced by 25%. 

What Are the Dose and Schedule of Kyprolis?

There are different dosing regimens for Kyprolis. Hydrate before and following Kyprolis as needed. Pre-medicate before all Cycle 1 doses and if infusion-related reactions develop or reappear. You and your doctor will determine which one of the following dosing regimens is best for you:  

Once-weekly Kd regimen 

20/70 mg/m2 by 30-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given at 20 mg/m2 on day 1 of cycle 1, then 70 mg/m2 is given on days 8 and 15. For cycle 2 and thereafter, Kyprolis is given at 70 mg/m2 on days 1, 8, and 15. 
  • No Kyprolis is given on days 16–28 of any cycle. 
  • Dexamethasone is given at a dose of 40 mg on days 1, 8, 15, and 22 of cycles 1–9. Thereafter, dexamethasone is given only on days 1, 8, and 15 of each cycle. 

Twice-weekly Kd regimen or Kyprolis monotherapy 

20/56 mg/m2 by 30-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given at 20 mg/mon days 1 and 2 of cycle 1 and, if tolerated, at 56 mg/m2 on days 8, 9, 15, and 16. During cycles 2–12, Kyprolis is given at 56 mg/m2 on days 1, 2, 8, 9, 15, and 16. For cycle 13 and thereafter, Kyprolis is given at 56 mg/m2 on days 1, 2, 15, and 16. 
  • No Kyprolis is given on days 17–28 of any cycle. 
  • Dexamethasone is not given with Kyprolis monotherapy. If you are on the Kd regimen, dexamethasone is given at 20 mg per day on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle. 

Twice-weekly Kyprolis monotherapy

20/27 mg/m2 by 10-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given at a dose of 20 mg/m2 on cycle 1, days 1 and 2. If tolerated, the dose is escalated to 27 mg/m2 on days 8, 9, 15, and 16 of the first cycle. In cycles 2–12, Kyprolis is given at 27 mg/m2 on days 1, 2, 8, 9, 15, and 16. For cycle 13 and thereafter, Kyprolis is given at 27 mg/m2 on days 1, 2, 15, and 16. 
  • No Kyprolis is given on days 17–28 of any cycle. 

Twice-weekly KRd regimen 

20/27 mg/m2 by 10-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given during cycle 1 at 20 mg/m2 on days 1 and 2, and if tolerated, at 27 mg/m2 on days 8, 9, 15, 16. 
  • In cycles 2–12, Kyprolis is given at 27 mg/m2 days 1, 2, 8, 9, 15, and 16. 
  • For cycle 13 and thereafter, Kyprolis is given at 27 mg/m2 on days 1, 2, 15, and 16. 
  • No Kyprolis is given on days 17–28 of any cycle. 
  • Revlimid is given at 25 mg on days 1–21 of each cycle. 
  • Dexamethasone is given at 40 mg on days 1, 8, 15, and 22 of each cycle. 

Once-weekly DKd regimen 

20/70 mg/m2 by 30-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given at 20 mg/m2 on day 1 of cycle 1 and, if tolerated, at 70 mg/m2 on days 8 and 15. Cycles 2–7 and thereafter, Kyprolis is given at 70 mg/m2 on days 1, 8, and 15. 
  • Darzalex IV is given at a dose of 8 mg/kg on days 1 and 2 of cycle 1 and, if tolerated, at 16 mg/kg on days 8, 15, and 22; alternatively, Darzalex Faspro SQ can be given as an abdominal injection under the skin at a dose of 1,800 mg/30,000 units on days 1, 8, 15, and 22. 
  • On days 1, 8, 15, and 22 of cycle 2, Darzalex IV is given at a dose of 16 mg/kg or Darzalex Faspro SQ is given at a dose of 1,800 mg/30,000 units. 
  • On days 1 and 15 of cycles 3–6, Darzalex IV is given at a dose of 16 mg/kg or Darzalex Faspro SQ is given at a dose of 1,800 mg/30,000 units. 
  • On Day 1 of cycle 7 and thereafter, Darzalex IV is given at a dose of 16 mg/kg or Darzalex Faspro SQ is given at a dose of 1,800 mg/30,000 units. 
  • Dexamethasone is given 30 minutes to 4 hours before Kyprolis and 1–3 hours before Darzalex IV. Dexamethasone is given at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of cycles 1 and 2. 
  • During cycles 3–6, dexamethasone is given at 20 mg on days 1 and 2; then 40 mg on day 8; then 20 mg on days 15, 16; then 40 mg on day 22. 
  • For cycle 7 and thereafter, dexamethasone is given at 20 mg on days 1 and 2; then 40 mg on days 8, 15, and 22. Alternatively, dexamethasone can be given on the same schedule as in the twice-weekly DKd regimen. 

Patients aged > 75 years receive dexamethasone at 20 mg after the first week of cycle 1. 

Twice-weekly DKd regimen 

20/56 mg/m2 by 30-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given on days 1, 2, 8, 9, 15, and 16 of each cycle. For cycle 1 only, patients receive a 20-mg/m2 dose of Kyprolis on days 1 and 2. 
  • For all subsequent cycles thereafter, Kyprolis is administered at a dose of 56 mg/m2
  • Darzalex is given at a dose of 16 mg/kg on days 1, 8, 15, and 22, of cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks during cycle 7 and thereafter. At the discretion of the treating doctor, there is an option of splitting the initial dose of Darzalex into two 8-mg/kg doses to be given on cycle 1, day 1 and cycle 2, day 2. 
  • Dexamethasone is given at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle. During weeks when patients receive Kyprolis and/or Darzalex, a split dose of 20 mg each of dexamethasone is given. 

Once-weekly Isa-Kd regimen 

20/56 mg/m2 by 30-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given at 20 mg/m2 once-weekly in cycle 1, then once every other week at 56 mg/m2 during in subsequent cycles. 
  • Sarclisa is given at 10 mg/kg as an IV infusion once-weekly in cycle 1 on days 1, 8, 15, and 22. In cycle 2 and beyond, the Sarclisa infusion is administered on days 1 and 15. The first infusion takes about 3–4 hours, the second infusion is about 2 hours, and the subsequent infusions are typically 75 minutes. 
  • Dexamethasone is given at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle as an IV infusion on days of Sarclisa or Kyprolis IV infusions, and taken orally by tablet on other days. 

Twice-weekly Isa-Kd regimen 

20/56 mg/m2 by 30-minute infusion: 

  • Each cycle is 28 days. 
  • Kyprolis is given at 20 mg/m2 on days 1 and 2 in cycle 1 to evaluate tolerability, then at the therapeutic dose of 56 mg/m2 on days 8 and 9 of cycle 1. Treatment schedule for subsequent cycles is Kyprolis at 56 mg/m2 given twice-weekly for 3 weeks, followed with a 12-day rest period. 
  • Sarclisa is given at 10 mg/kg as an IV infusion once-weekly in cycle 1 on days 1, 8, 15, and 22. In cycle 2 and beyond, the Sarclisa infusion is administered on days 1 and 15. The first infusion takes about 3–4 hours, the second infusion is about 2 hours, and the subsequent infusions are typically 75 minutes. 
  • Dexamethasone is given at a dose of 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle as an infusion on days of Sarclisa or Kyprolis IV infusions, and taken orally by tablet on other days. 

Treatment with Kyprolis may be continued until disease progression or unacceptable toxicity. Your doctor will evaluate your response to Kyprolis and your tolerance of your medications to determine how many cycles of treatment are right for you. 

Your doctor may make schedule adjustments, reduce your dose of Kyprolis, or stop treatment temporarily until a side effect improves, and then resume again. A side effect is any unwanted or unexpected effect caused by a drug, also known as an adverse reaction or adverse event (AE). 

Cautions with the Use of Kyprolis  

Caution must be exercised with higher doses of Kyprolis. You must be monitored carefully for infusion-related reactions (IRR), which can occur immediately following an infusion or up to 24 hours after. Complications may include the following: 

  • fever 
  • chills 
  • joint pain 
  • muscle pain 
  • facial flushing 
  • facial swelling 
  • vomiting 
  • weakness 
  • shortness of breath 
  • low blood pressure 
  • fainting 
  • chest tightness 
  • chest pain 

Promptly report to your doctor any side effects that you experience in the days after your infusion of Kyprolis. 

Administration of dexamethasone before the infusion of Kyprolis reduces the incidence and severity of IRR. Additional precautions with the use of Kyprolis include the following: 

  • Talk with your doctor about being pretreated with dexamethasone prior to your cycle 1 dose and if infusion reaction symptoms develop or reappear. 
  • Your doctor will give you instructions specific to your case about how much water you should drink before your first infusion of Kyprolis. 
  • Talk with your doctor about receiving medication to prevent blood clots if you are taking Kyprolis in combination with dexamethasone or with Revlimid and dexamethasone. Your doctor will choose the appropriate medication for you based on an assessment of your individual risk factors for blood clots. 
  • Talk with your doctor about receiving antiviral therapy to decrease the risk of herpes zoster. 
  • If you are receiving hemodialysis for kidney failure, you should receive Kyprolis after the hemodialysis procedure. 
  • Kyprolis can cause harm to a fetus if it is administered to a pregnant woman. Females of childbearing potential should avoid becoming pregnant during treatment with Kyprolis, and should not take Kyprolis while breastfeeding. 

Possible Side Effects of Kyprolis 

Good communication with your doctor is extremely important while you are receiving treatment for myeloma. 

Discuss your questions or concerns with your doctor and alert your doctor promptly if you experience any side effects. 

The most common side effects, those seen in 30% or more of the patients who received Kyprolis in clinical trials, include fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and fever. 

Kyprolis may also cause dizziness, fainting, and/or a drop in blood pressure. Caution is advised if you are operating machinery, including automobiles. 

In clinical trials, the incidence of side effects was greater in patients age 75 or older. 

Serious adverse events reported to the FDA by researchers during clinical trials of combination therapies with Kyprolis included the following: 

  • Renal (kidney) insufficiency, including renal failure, occurred in approximately 9% of patients treated with Kyprolis. 
  • Cardiac failure events, such as congestive heart failure, pulmonary edema, and decreased heart ejection fraction occurred in 8% of patients. 
  • Arrhythmias occurred in 8% of patients, the majority of which were atrial fibrillation and sinus tachycardia. 
  • Pulmonary arterial hypertension (abnormally high blood pressure in the arteries of the lungs) occurred in 2% of patients. 
  • Liver failure, including fatal cases, occurred in less than 1% of patients. 

Some occurrences of kidney failure in myeloma patients receiving Kyprolis have resulted in death. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory myeloma who received Kyprolis as a single therapy. Your kidney function will be monitored regularly while you are taking Kyprolis, and your dose of Kyprolis will be reduced or withheld as needed. 

Death due to cardiac arrest has occurred within a day of Kyprolis administration. Patients with pre-existing heart conditions may be at greater risk for cardiac complications. Although underlying heart disease does not exclude use of Kyprolis, patients with New York Heart Association (NYHA) Class III and IV congestive heart failure, as well as those with uncontrolled conduction abnormalities or a history of heart attack within the previous six months, were excluded from clinical trials. Prescribing information for Kyprolis recommends that patients be monitored for cardiac complications and managed promptly. 

Kyprolis can cause other rare but serious side effects. You must report any changes in your health promptly to your medical team so that they can monitor your signs and symptoms. 

Contact your doctor immediately if you experience any of the following: 

  • fever 
  • chills 
  • shivering 
  • chest pain 
  • cough 
  • swelling of the feet or legs 
  • bleeding 
  • bruising 
  • weakness 
  • headaches 
  • confusion 
  • seizures 
  • loss of sight 
  • shortness of breath 
  • dizziness 
  • lightheadedness 
  • fainting 
  • any other potential side effects 

Any concerns or questions about these issues should be discussed with your doctor or nurse, who can provide more information in greater detail about these and other possible side effects. Speak with your doctor or nurse if you notice ANY changes in your health while you are taking Kyprolis or any other medication.

Fatigue 

Fatigue is the most common side effect associated with Kyprolis therapy, and one that can appear with increasing severity over time. For further information about fatigue, read the IMF’s publication Understanding Fatigue

Prevention and treatment of fatigue 

Discuss your fatigue with your doctor and healthcare team. Management of fatigue may include supportive care as determined by your physician. The effects of fatigue may be minimized by maintaining: 

  • A moderate level of activity, neither too much nor too little, 
  • A healthy diet and proper fluid intake, 
  • A consistent sleeping schedule with enough rest. 

Anemia 

Red blood cells contain hemoglobin, a protein that carries oxygen to the body’s tissues and organs. Anemia is usually defined as a decrease in hemoglobin < 10 g/dL or as a decrease of ≥ 2 g/dL from the normal level for an individual. More than 13–14 g/dL is considered normal. Low levels of oxygen in the body may cause shortness of breath and feelings of exhaustion. Many newly diagnosed myeloma patients have anemia. 

Anemia may or may not develop over the course of treatment with Kyprolis. 

Prevention and treatment of anemia 

Your doctor will determine how to treat your anemia. Options may include adjusting medication, blood transfusions, or erythropoietic (red blood cell-making) agents. 

Nausea 

Nausea may occur while taking Kyprolis, but is typically not severe. If vomiting occurs and leads to dehydration, a patient may experience dizziness, lightheadedness, or fainting. Medical treatment may be required for dehydration. 

Prevention and treatment of nausea 

Precautions should be taken to prevent dehydration caused by vomiting. Drink a sufficient amount of water and other fluids. Seek medical advice if you experience dizziness, lightheadedness, or fainting. Your physician may administer anti-emetic medication (to prevent vomiting) or intravenous hydration, as required. 

Thrombocytopenia 

Thrombocytopenia is defined as a low number of platelets in the blood. Platelets help blood to clot; fewer platelets can lead to easier bruising, bleeding, and slower healing. The “normal” level varies from laboratory to laboratory. For example, the “normal” level is ≥ 150,000 platelets per microliter of circulating blood. If the platelet count is less than 50,000, bleeding problems could occur. Major bleeding is usually associated with a reduction to less than 10,000. 

Patients taking Kyprolis often experience thrombocytopenia. The platelet level decreases with treatment but, after the required interval between doses, should return to the baseline level by the beginning of the next cycle. 

Prevention and treatment of thrombocytopenia 

You should inform your physician if you experience excessive bruising or bleeding. Management may include lowering or withholding the next dose of Kyprolis. Platelet transfusions may be ordered at your doctor’s discretion. 

Dyspnea 

Dyspnea is the medical term for shortness of breath, often described as an intense tightening in the chest, air hunger, difficulty breathing, or breathlessness. Dyspnea can be caused by a host of medical problems, including anemia, pneumonia, or a pulmonary embolism. 

It is urgent that you contact your doctor if there is a sudden change in your breathing. There have been reports of heart and lung disorders in patients receiving Kyprolis, and shortness of breath can be a sign of a serious problem and must be reported to your doctor immediately. 

Prevention and treatment of dyspnea 

Appropriate measures to prevent and treat shortness of breath depend on the cause of this problem. Your doctor will assess your heart and lungs and may order more tests before deciding upon the course of action. 

Diarrhea 

Diarrhea is defined as 3 or more loose stools per day. Severe diarrhea is defined as 7 or more loose stools per day, requiring treatment with intravenous fluids or hospitalization. Diarrhea may occur while taking Kyprolis. Dizziness, lightheadedness, or fainting may occur due to dehydration caused by either excessive or persistent diarrhea. 

Prevention and treatment of diarrhea 

Precautions should be taken to prevent dehydration caused by either excessive or persistent diarrhea. You should maintain a proper level of hydration by drinking a sufficient amount of water and seek medical advice if you experience dizziness, lightheadedness, or fainting. Your physician may administer antidiarrheal medication or IV hydration, as required. 

Fever 

An oral temperature greater than 100.4°F (38°C) needs to be further evaluated immediately. Fever can signal bacterial or viral infection, an adverse reaction to a drug, or in rare cases, an aggressive myeloma relapse. Since fever can be a sign of a life-threatening condition, you should report this problem immediately. The combination of fever and shortness of breath is of special concern. If this occurs, it is urgent that the patient is seen by a healthcare professional to receive immediate treatment. 

Prevention and treatment of fever 

Your doctor will perform tests to determine the cause of the fever and will take appropriate action, which may include one or more of the following: 

  • Antibiotic therapy, 
  • Antiviral therapy, 
  • Treatment with acetaminophen, 
  • Hydration, or 
  • Change in therapy. 

Other possible side effects of Kyprolis

Less frequent side effects that may occur with Kyprolis include tumor lysis syndrome (TLS), lung disorders, and liver problems. Alert your doctor promptly if you experience the following: 

  • shortness of breath 
  • flu-like symptoms (for example, fever, chills, or shivering) 
  • chest pain 
  • cough 
  • dizziness, lightheadedness, or fainting spells 
  • swelling of the feet, ankles, or legs 

Good communication with your healthcare team is essential while you are receiving therapy for myeloma. Ask your doctor for a number you can call if you need immediate help, especially after office hours and on the weekend. An important part of being a patient is to report side effects promptly and clearly. The IMF is here to help facilitate the best possible dialogue with your healthcare team. 

Kyprolis in Clinical Trials

Kyprolis is being studied throughout the myeloma disease course in numerous clinical trials and as a part of different combination therapies.

In December 2023, the results from the IsKia phase III clinical trial were  presented at a plenary session of the annual meeting of the American Society of Hematology (ASH). The study evaluated 302 patients with newly diagnosed multiple myeloma (NDMM) who were eligible for an autologous stem cell transplant (ASCT). Patients were randomized to two study arms with 151 patients in each arm.

One arm received Kyprolis, Revlimid, and dexamethasone [KRd]. The other arm received Sarclisa® (isatuximab-irfc) plus KRd [Isa-KRd]. This clinical trial assessed efficacy and safety of Isa-KRd as pre-ASCT induction therapy and post-ASCT consolidation therapy.

Compared to  KRd alone, Isa-KRd induction and consolidation significantly increased the rates of MRD-negativity in every treatment phase and with no new safety concerns. This result was also true in patients with high-risk multiple myeloma (HRMM). 

To learn about clinical trials that may be enrolling myeloma patients, please visit the National Cancer Institute website clinicaltrials.gov or contact the IMF InfoLine.


Additional information

Official drug manufacturer's website for Kyprolis (carfilzomib)

Kyprolis Patient Support Program

 


 


The International Myeloma Foundation medical and editorial content team

Comprised of leading medical researchers, hematologists, oncologists, oncology-certified nurses, medical editors, and medical journalists, our team has extensive knowledge of the multiple myeloma treatment and care landscape.

Additionally, the content on this page is medically reviewed by myeloma physicians and healthcare professionals.   

Last Medical Content Review: June 11, 2024

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