All About Kyprolis (Carfilzomib)

All about Kyprolis or Carfilzomib. So Kyprolis, which is also called Carfilzomib, is a second generation proteasome inhibitor. Velcade is the first generation proteasome inhibitor, whereas Kyprolis is a second generation. That means basically it is more potent and it is irreversible. Whatever proteasome inhibition Kyprolis is doing in the cancer cells, it cannot be reversed. It is irreversible and it is more potent and it is more selective. What is the mechanism of action of Kyprolis? It is another proteasome inhibitor, as I've mentioned. Proteasomes are protein complexes that have enzymes. Enzymes means chemicals to take care of proteins that are defective or degraded. Defective proteins are essentially being removed by these proteasomes. So when these proteasomes are inhibited by the Kyprolis, the cancer cells suffer. The cell cycle, which is their life cycle, to produce more cells and to make the cancer cells grow is disrupted. Eventually it leads to the death of these cancer cells by something called apoptosis. Apoptosis means programmed cell death. Basically the cancer cells die. So that's how the Kyprolis works by being a proteasome inhibitor. And the benefit of Kyprolis over Velcadis, the inhibition of these proteasomes by Kyprolis is irreversible and it is more potent. It's more stronger. When is Kyprolis used? Kyprolis is used for the treatment of relapsed refractory multiple myeloma. It is indicated for the treatment of relapsed refractory multiple myeloma. It is given through the vein intravenously. What should I know about my Kyprolis infusion? Kyprolis patients are encouraged to hydrate themselves well for at least like 48 hours before each dose. And also, as I've mentioned before, patients will be given 250 to 500 ml of fluids, IV, before the medication is given. The infusion is not long. It's given over like 30 to 60 minutes. And patients usually get premedicated with Tylenol or Benadryl. Why is it important to drink water while taking Kyprolis? Because Kyprolis can cause kidney failure. It can cause some amount of kidney dysfunction. So by taking the fluids, you're actually keeping the kidneys flushed. You're reducing the chance of this chemical, this drug, the chemotherapy drug Kyprolis, to cause kidney failure. You're reducing the risk by drinking plenty of fluids as well as by getting IV fluids before giving the medication. Can someone who is on dialysis take Kyprolis? So it's been used in dialysis patients. However, we usually tend to do it on non-dialysis days because if they take the medication and then get dialysis, then the efficiency might be lower. So we usually do these medications on off-dialysis days. What is the schedule used for Kyprolis? The schedule is usually days 1, 2, 8, 9, 15, 16 of a 28-day cycle. So to put it simply, it's a four-week cycle. Patients get treated two consecutive days of every cycle for the first three cycles and then they get the fourth cycle off. Kyprolis can also be given once a week. Your doctor will advise as to which schedule is right for you based on your characteristics and preferences as a patient. What is the dose of Kyprolis? The dosage depends on whether it is being given just with dexamethasone or whether it is being given with some other medication like Revlimid. If it is given just with dexamethasone, the dosage increases after the first two days. Day 1 and 2, when the treatment is being started, the dosage is just 20 milligram per square meter. If Kyprolis is being given just with dexamethasone, then from day 8, the dosage increases to 56 milligram per square meter. However, if Kyprolis is being added to something like Revlimid, then the dosage would be lower. From day 8 and 9, the dosage increases to just 27 milligram per square meter. The first two days, the dose is standard though, 20 milligram per square meter. Kyprolis can also be given with other anti-myeloma agents. The right dose and schedule of Kyprolis used in combination therapies will be based on your characteristics and preferences as a patient. Listed here are the NCCN guidelines that incorporate Kyprolis in myeloma treatment. So, once weekly dosing of Kyprolis has been approved, it's given at a higher dose, 70 milligram per square meter. But the side effects could be a little more or rather to put it in another way, patients who are elderly or frail might not be able to tolerate it well at the higher dose. But for fit patients, once weekly dosing is approved at a dose of 70 milligram per square meter. So Kyprolis is used for the treatment of relapsed refractory multiple myeloma. It can be given alone with dexamethasone or it could be combined with other medications like Revlumate or Pomelist, which are immunomodulated drugs taken orally. Of course, in clinical trials, they are testing it with other medications also like Darzelex, Selenaxor, newer medications, but they are still in the clinical trials. On August 20th, 2020, the Food and Drug Administration approved Kyprolis and Darzelex in combination with dexamethasone for adult patients with relapsed or refractory myeloma who have received one to three lines of therapy. What are the common side effects of Kyprolis? Kyprolis has a side effect profile which is different from Velcade. Good thing is the peripheral neuropathy risk, risk of peripheral neuropathy affecting the nerve function is much lower with Kyprolis. The side effects which are exclusive to Kyprolis include diarrhea. It can cause some diarrhea, although it is lower than Velcade. Precautions should be taken to prevent dehydration caused by diarrhea. Drink plenty of water and seek medical advice if you are feeling lightheaded, dizzy, or have fainted. Diarrhea can be managed with over-the-counter antidiarrheals such as Imodium and IV hydration. It can cause heart failure. It can cause hypertension. It can make the blood pressure go up. It can sometimes cause pneumonitis which is inflammation in the lungs. It can also cause kidney failure. So patients who get Kyprolis always receive 250 to 500 ml milliliters of fluids before the dose, before the medication is given. So it's important to monitor their kidney function, their blood pressure, their heart and lung function. Taking good history and examining the heart and lungs and monitoring the kidney function in the blood work is very important. As I've mentioned, it is indicated for the treatment of relapsed refractory multiple myeloma. Even Kyprolis has the risk of causing shingles. So patients who are taking Kyprolis should take prophylaxis with acyclovir. Standard dose is 400 mg twice daily. The dosage should be reduced if patients have renal dysfunction or renal failure. Additional side effects associated with Kyprolis are low platelet counts which can cause bleeding and anemia or low red blood cell counts which can cause fatigue, insomnia, nausea, cough and fever. You should contact your doctor right away if you have any of the following symptoms. Shortness of breath, trouble breathing, prolonged unusual or excessive bleeding, yellowing of the skin and or eyes, jaundice, headaches, confusion, dizziness or loss of balance, trouble talking or walking, weakness on one side of the body, seizures or loss of sight, as well as any other side effect that bothers you or does not go away. Women should not receive Kyprolis if they are pregnant or breastfeeding. Is shortness of breath a common side effect? Not a common side effect only if it affects the heart or the lungs. Only if it causes either heart failure or pneumonitis. Pneumonitis means inflammation of the lungs. We look at the history to see like if the patient has risk factors or had heart disease or heart attacks before. We do an echocardiogram which is an ultrasound of the heart to make sure that they have good cardiac function before we start the medication. And while patients are getting it, we don't necessarily follow them with echocardiograms but we pay close attention if they are developing any symptoms of heart failure such as retaining more fluid, more weight gain, getting short of breath when they are walking around and also examination of their heart and lungs at every visit. And if there is any suspicion of heart failure, we evaluate it with an echocardiogram and of course x-ray too, chest x-ray. What do you do if there is heart failure? We usually stop the medication depending on like how bad it is. We often tend to discontinue the medication and of course over a period of time if the heart function improves to normal then it could be reintroduced but otherwise we usually stop the medication. If an individual stopped responding to Velcade, is Kyprolis a good option? Kyprolis can be used in patients who are refractory to Velcade because Kyprolis is a second generation proteasome inhibitor meaning it is potent, more potent than Velcade and it is irreversible. So yes, Kyprolis can be used in patients who become refractory to Velcade. Sometimes you need someone who knows what you are going through. That is why Amgen offers the Amgen Assist 360 Nurse Ambassador program. Your Amgen Nurse Ambassador will be your single point of contact so you can get the kind of support you need when you need it. Amgen Nurse Ambassadors can refer you to independent non-profit organizations that may provide community resources, one-on-one counseling services and local support groups. Learn how Kyprolis may be covered and find programs that may make treatment more affordable such as Amgen First Step. Work with Amgen Nurse Ambassadors to answer questions concerning your Amgen medication.