Kyprolis® (carfilzomib) for injection is a type of prescription medicine (a proteasome inhibitor) used to treat patients with multiple myeloma. It is approved for the following:
- In the U.S. and in Europe for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three previous treatments. For these patients, Kyprolis is used combination with Revlimid (lenalidomide) and dexamethasone, or in combination with just dexamethasone.
- In only the U.S. as a single agent (alone) for the treatment of patients with relapsed or refractory MM who have received one or more lines of therapy.
What are the indications for treatment with Kyprolis?
Kyprolis is currently approved by the US Food and Drug Administration (FDA) in the following settings:
- Kyprolis and Darzalex® (daratumumab) and the steroid dexamethasone irreversible bond with the proteasome in the nucleus of each myeloma cell. fIt is used for the treatment of patients with relapsed or refractory myeloma who have received one or more prior lines of therapy.
- Kyprolis, Revlimid® (lenalidomide) and dexamethasone (KRd) is used for the treatment of patients with relapsed or refractory myeloma who have received one to relapsed or refractory myeloma who have received one to three prior lines of therapy.
- Kyprolis and dexamethasone (Kd) is used for the treatment of patients with relapsed or refractory myeloma who have received one to three prior lines of therapy. Kyprolis as a single agent for the treatment of patients with relapsed or refractory myeloma who have received one or more prior lines of therapy.
How does it work?
Kyprolis forms an irreversible bond with the proteasome in the nucleus of each myeloma cell. When Kyprolis inhibits proteasomes, the normal balance within the cell is disrupted. When proteasomes are inhibited, cancer cells stop dividing and undergo apoptosis (cell death). They also stop producing chemicals to stimulate other cancer cells. Cancer cells are more sensitive to these effects than normal cells, so the cancer cells die while normal cells are able to recover.
How is Kyprolis given?
Kyprolis is a freeze-dried powder, which must be reconstituted (dissolved) before it is administered. Kyprolis is administered intravenously (IV) at a doctor’s office, hospital, or clinic. At the discretion of the treating physi-cian, hydration may be given before and after each dose of Kyprolis, based upon the patient’s tolerance of Kyprolis, the dose of Kyprolis, and the duration of infusion time. Caution must be exercised to avoid fluid overload.
What are the dose and schedule of Kyprolis?
There are different dosing regimens for Kyprolis. You and your doctor will determine which one of the following dosing regimens is best for you:
Once-weekly Kd regimen
- Kyprolis is given at 20 mg/m2 for the first dose (Cycle 1, day 1), then 70mg/m2 is given once weekly on days 8 and 15.
- From Cycle 2 onward, Kyprolis is given at 70 mg/m2 on days 1, 8, and 15 of each 28-day Cycle.
- 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 28-day Cycle.
Twice-weekly Kd regimen or Kyprolis monotherapy
20/56 mg/m2 by 30-minute infusion
- Kyprolis is given at 20 mg/m2 on days 1 and 2 of Cycle 1.
- Then, if tolerated, the Kyprolis dose is escalated to 56 mg/m2 on days 8, 9, 15, and 16.
- From Cycle 2–12, Kyprolis is given at 56 mg/m2 On days 1, 2, 8, 9, 15, and 16 of each 28-day Cycle.
- From Cycle 13 onward, Kyprolis is given at 56 mg/m2 on days 1, 2, 15, and 16 of each 28-day Cycle.
- 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 28-day Cycle.
Twice-weekly Kyprolis monotherapy
20/27 mg/m2 by 10-minute infusion
- 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/m2on days 1, 2, 8, 9, 15, and 16 of each 28-day Cycle.
- From Cycle 13 onward, Kyprolis is given at 27 mg/m2 on days 1, 2, 15, and 16 of each 28-day Cycle.
- No Kyprolis is given on days 17–28 of any Cycle.
Twice-weekly KRd regimen
20/56 mg/m2 by 30-minute infusion
- Kyprolis is given on days 1, 2, 8, 9, 15, and 16 of each 28-day treatment Cycle.
- For Cycle 1 only, patients receive a 20-mg/m2 loading dose of Kyprolis on days 1 and 2.
- For all subsequent treatments 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.
- It is given at every 2 weeks during Cycles 3 to 6,
- Then, it is given every 4 weeks during Cycle 7 and beyond.
- For patient convenience, the initial dose of Darzalex is split into two 8-mg/kg doses and 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 treatment Cycle.
- During weeks when patients receive Kyprolis and/or Darzalex, a split dose of 20 mg each of dexamethasone was given.
Possible side effects
Fatigue is the most common side effect associated with Kyprolis therapy, one that can appear with increasing severity over time. See the IMF publication, Understanding Fatigue, for further information about this topic and about anemia.
Red blood cells contain hemoglobin, a protein that contains iron and transports oxygen from the lungs to the body’s organs and tissues. When a patient has anemia, the result is low levels of oxygen in the body, which may cause shortness of breath and feelings of exhaustion. As with fatigue, anemia is not an immediate effect of Kyprolis, but one that appears with duration of treatment.
Nausea may occur while taking Kyprolis, but it is usually not severe. If vomiting occurs and leads to dehydration, the patient may experience dizziness, lightheadedness, or fainting. Medical treatment may be required for dehydration.
Thrombocytopenia (decreased platelet levels)
Patients taking Kyprolis often experience thrombocytopenia – a lowered level of platelets in the blood. Platelets help blood to clot after an injury; fewer platelets can lead to bruising, bleeding, and slower healing. Kyprolis causes the platelet count to drop, but the required interval between doses allows time for the platelet count to return to the baseline level by the beginning of the next cycle.
Dyspnea (shortness of breath)
Shortness of breath can result from many causes, including heart and/or lung problems, anemia, deconditioning (lack of exercise), and obesity. If there is a sudden change in your breathing, it is especially important that you contact your doctor right away. There have been reports of heart and lung disorders in patients receiving Kyprolis, so shortness of breath can be a sign of a serious problem, and should be reported to your healthcare providers promptly.
Diarrhea may occur while taking Kyprolis. Dizziness, lightheadedness, or fainting may occur due to dehydration caused by either excessive or persistent diarrhea.
Fever can signal bacterial or viral infection, an adverse reaction to a drug, or in rare cases, an aggressive multiple myeloma relapse. Since fever could be the 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, the patient must have immediate treatment.
Other side effects
Other side effects can occur with Kyprolis, but they are much less frequent. These side effects include heart problems, tumor lysis syndrome (TLS), lung disorders, and liver problems. You will be monitored carefully during treatment for any signs of these problems. If you have questions or concerns about any of these potential issues, you should discuss them with your treating physician.
Kyprolis in clinical trials
Kyprolis is being studied throughout the myeloma disease course in numerous clinical trials. 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.
Official drug manufacturer's website for Kyprolis (carfilzomib).
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