All About Kyprolis (Carfilzomib) - Updated 2025

What is Kyprolis?

Kyprolis, also called carfilzomib, is a proteasome inhibitor. And proteasome inhibitors are a staple of treatment in multiple myeloma. Velcade or bortezomib is a first generation proteasome inhibitor and is considered a reversible proteasome inhibitor, whereas Kyprolis or carfilzomib, is a second generation protease inhibitor. It is an irreversible proteasome inhibitor. So patients who have had exposure or treatment to Velcade or bortezomib at the beginning will still tend to respond to Kyprolis or carfilzomib in later on. And that is why we consider it to be a more potent proteasome inhibitor overall.

Kyprolis was FDA approved on July 20th, 2012. This drug was approved under the FDA's Accelerated Approval Program, which allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

To learn more about surrogate endpoints, watch the HealthTree University video on surrogate endpoints found in our clinical trial class.

How do proteasome inhibitors like Kyprolis work?

Proteasomes are intracellular machinery that allowed for the degradation of proteins. And in so doing they allow a protein's normal functioning by getting rid of junk proteins. A proteasome inhibitor prevents that normal function. And so the otherwise proteins that would be shed or accumulate and cause dysfunction and ultimately death to that cell. In the case of multiple myeloma, that is desirable because we are trying to kill that cell. And so proteasome inhibitors promote cell death.

If you would like a better understanding of how proteasome inhibitors do their job, watch our proteasome inhibitor lesson in the Classes of drugs course.

How is Kyprolis administered?

Kyprolis is administered through the intravenous route. So it requires an IV or a port or a pick line, something that gives you access to the veins and is administered through that that way. It's usually a 30 to 60 minute infusion. And typically people are given some sort of intravenous fluids, either 250ml up to about 500ml most commonly. And then at the beginning. People are also often pre-meditated with Tylenol or Benadryl In general, we recommend not only the intravenous hydration when people are getting Kyprolis, but also oral hydration because it can be harsh to the kidney and secondarily can be harsh towards the heart as well. So the benefit of the hydration is that it reduces the injury to those organs.

Can patients who are on dialysis take Kyprolis?

Interestingly, yes, it has been shown that people on dialysis can in fact receive Kyprolis safely. It is typically given after a patient's dialysis session.

Can individuals with heart disease receive Kyprolis safely?

One of the most famous side effects of  Kyprolis is that it can cause heart failure. And so that is something that we do look for, watch for, and are concerned about prior to beginning Kyprolis, a patient will usually have an echocardiogram to ensure that the pump function of the heart is intact and is sufficient to be given the challenge of Kyprolis. And then while on Kyprolis, if there is any concern for any burgeoning heart failure, then that is what will be reinvestigated with another echocardiogram. And if a patient has something like, unexplained leg swelling or shortness of breath, again, it would be something that that is considered.

When is Kyprolis recommended as a treatment option?

In general, we tend to use Kyprolis in the second line setting or beyond. But I should note that it is also commonly used in the front line setting. In the typical route, patients will usually have an exposure to Velcade or bortezomib first, and secondarily this other proteasome inhibitor. Kyprolis (Carfilzomib).

Is Kyprolis used in combination with other anti myeloma therapies?

Kyprolis has been used in numerous combinations, with multiple myeloma and triplets and quadruplets as well. Some of the more famous combinations are Daratumumab, Kyprolis, dexamethasone. Daratumumab, Kyprolis,  lenalidomide also called revlimid dexamethasone and beyond.

The National Comprehensive Cancer Network guidelines include more examples of how Kyprolis is used in combination with other therapies. In this HealthTree University lesson, we use the latest 2025 guidelines. If you are watching this lesson after 2025, check the NCCN website for any changes. Listed here are the NCCN guidelines that incorporated Kyprolis in myeloma treatment. This is the guideline for primary therapy in both transplant eligible and non-eligible patients. This is for patients in maintenance therapy. The preferred guideline for relapsed or refractory multiple myeloma after 1 to 3 lines of therapy is as follows. This is for patients that are anti-CD38 monoclonal antibodies refractory. This is for patients that are Velcade refractory. This is for patients that are Revlimid refractory. The NCCN guideline for relapsed or refractory myeloma patients also contains other recommended treatment regimens beside the ones previously mentioned, and suggests the use of Kyprolis in certain situations.

What is the dose and schedule of Kyprolis?

Kyprolis has numerous dosing schedules, and I should note that there's a bit of a separation between what it was originally studied in, in clinical trials versus what occurs in the real world. So typically patients are given a priming dose of 20mg/m² on days one and two. And then the dose that is as high as 70mg/m² once a week. Overall, there are different dosing schemes depending upon the trial that the physician is following to treat that given patient. And so there will be a great deal of diversity in what a patient sees. We do have real world data to support that 56mg/m², given once weekly, is not inferior to the 70mg/m² once weekly. Nor does it have the same side effects as the 70mg/m². And the twice weekly dosing similarly does not had add any further potency compared to the once weekly dosing. And so overall, there's been a tendency to give Kyprolis in a once weekly setting up to that dose of 56mg/m². And to be clear, the once weekly versus twice weekly and the different dosing schemes from the 27, 56 to 70 are all bonafide dosing schemes and are appropriate for patients. All of them are tailored to what the patient is in front of the physician needs.

What is the typical cycle of Kyprolis?

Usually Kyprolis is given in 21 to 28 day cycles. Usually the cycles are continuous, so once the cycle completes, the next one begins. Now, that is not necessarily imply that a patient is getting that dose every single time. For instance, on the fourth week of a four week cycle, the dose can be omitted. Again, this is tailored based on the patient. And so a patient may experience the cycle differently depending upon that scheme.

Kyprolis dosing can be very complicated. Doses will vary depending on  which other anti-myeloma therapies  Kyprolis is paired with. and whether you are receiving it once or twice a week.  A detailed explaination of Kyprolis dosing is found at the end of the lesson. Chapters will be included so you can quickly jump to the combination you want to learn more about.

What are infusion related reactions?

Infusion related reactions refer to those reactions that specifically occur around the time of the infusion itself. And that can be some things like flushing sometimes fevers, chills, redness, maybe even shortness of breath when those occur, they're usually infusion reaction protocols that institutions will follow where the drug will be stopped. A patient will be put on a monitor. Sometimes they will begin to touch things as Tylenol, Benadryl and steroids and watch thereafter. And to note, just because someone does have an infusion related reaction does not mean that they cannot receive the drug. It just may mean that the dose or the speed at which it's given may need to be adjusted. And often patients do tolerate as people as they get the doses more. where they may have an initial reaction. But that is not seen on the second, third or fourth administrations.

What premedications are administered prior to Kyprolis?

In addition to the intravenous fluids that are given the 250ml to up to 500ml. They are also typically given Tylenol, Benadryl at the beginning.

Are there any other side effects you would like to mention?

The most prominent side effect that we worry about is heart failure, where it can cause and exacerbate heart failure. And so prior to the initiation of Kyprolis, usually an echocardiogram is done to ensure that the pump function of the heart is adequate and that someone is safe to try Kyprolis. Beyond that, it can cause renal failure and worsen kidney function overall.

So that is something that is watch for and that is where the the hydration is also very important. And beyond that there are such other things such as fatigue, low blood counts, changes to people's liver function as well that are watched for and that are seen.

Your treating physician will order regular blood work to monitor your blood counts and organ function.

Rarely, diarrhea is seen.Neuropathy is not nearly as common with Kyprolis. 

The following side effects have been reported when Kyprolis is used in combination therapy. Low red blood cell count. Diarrhea. High blood pressure. Tiredness. Upper airway infection. Low platelets. Fever. Cough. Difficulty breathing and sleeplessness.

Call your doctor if you have symptoms of low blood pressure, dizziness, tiredness, and fainting spells. Do not drive or operate machinery if you experience any of these symptoms.

Also, you should contact your doctor right away if you have any of the following. Shortness of breath or trouble breathing, prolongs unusual or excessive bleeding. Yellowing of the skin and or eyes. Headaches, confusion, dizziness or loss of balance, troubling talking or walking, weakness on one side of the body, seizures or loss of sight. Any other side effect that bothers you or does not go away.

For more information, watch our Managing Side Effects course and refer to HealthTree’s Side Effects solution tool on HealthTree.org.

What prophylactic medication should be prescribed when taking Kyprolis?

One prophylactic medication that we will often prescribe is acyclovir, and we typically will give it at a dose of 400mg, twice daily. But to note, that will be adjusted based on the patient's kidney function.

And we do so to prevent shingles. And it also offers protection against other herpesviridae viruses. Kyprolis like other drugs, will affect a person's immunity. And any degree of immunocompromised can allow shingles to emerge. And so this is one way to prevent that.

Do I still need to take acyclovir if I received the shingles vaccine? 

In general, we do recommend that patients receive the shingles vaccinations But even if they have received that, we typically do recommend and advocate that people still be given acyclovir not just because of the shingles protection itself, but because of the other protection against herpesviridae viruses.

If I stopped responding to Velcade, will I still be able to respond to Kyprolis?

If a patient has been previously treated with Velcade or bortezomib, carfilzomib or Kyprolis, use is still a very bonafide option. It is a second generation proteasome inhibitor versus Velcade, which is a first generation proteasome inhibitor. And does have strong evidence to support its efficacy even after someone is no longer, adequately treated by Velcade.

The followings include the Kyprolis dosing protocols.

Darzalex, Kyprolis, Dexamethasone can be given once or twice weekly. The FDA approved once weekly dose of 70mg/m² of Kyprolis after a 20mg/m² dose, is given on day one of cycle one to evaluate tolerability. This dose is given one day each week for three weeks, followed with a 13 day rest period as part of a 28 day treatment cycle. Kyprolis is continued until disease progression or unacceptable toxicity.

When Darzalex, Kyprolis, dexamethasone is given twice weekly, a lower dose of 56mg/m² is given after a 20mg/m² dose is given on day one of cycle one to evaluate tolerability. This dose is given two consecutive days each week for three weeks, followed with a 12 day rest period as part of a 28 day treatment cycle. Kyprolis is continued until disease progression or unacceptable toxicity.

The FDA approved dose of isatuximab, Kyprolis, Dexamethasone is 56mg/m² on two consecutive days each week for three weeks after a 20mg/m² dose is given on day one of cycle one to evaluate tolerability. There is a 12-day rest period as part of a 28-day treatment cycle. Kyprolis continues until disease progression or unacceptable toxicity occurs.

When Kyprolis is used with revlimid and dexamethasone, this is the treatment schedule administer a priming dose of Kyprolis. On days one and two of cycle one. The target dose of Kyprolis starts on day eight of cycle one, if the priming dose is tolerated. Kyprolis is administered on two consecutive days each week for three weeks followed by a 12 day rest period as part of a 28 day treatment cycle. For cycles 13 to 18, omit the day 8 and 9 doses of Kyprolis. Kyprolis should be discontinued after cycle 18 when given in combination with Rd. When Kyprolis is used in combination with dexamethasone, the dosing is flexible.

Kyprolis can be used with just dexamethasone either once or twice a week. For the twice weekly dosing schedule administer Kyprolis 56mg/m² on two consecutive days each week for three weeks after a 20mg/m² priming dose is given on days one and two of cycle one to evaluate tolerability. A 12 day rest period is given after week three as part of a 28 day treatment cycle. Kyprolis is continued until disease progression or unacceptable toxicity occurs.

Kyprolis can also be given with dexamethasone once weekly. The FDA approved dose as Kyprolis is 70mg/m². One day each week for three weeks after a 20mg/m², priming dose is given to evaluate tolerability. A 13 day rest period is given after week three of each cycle as part of a 28 day treatment cycle. Kyprolis is continued until disease progression or unacceptable toxicity occurs. Keep in mind, real world data may even suggest other dosing schedules. There is a tendency to give Kyprolis a once weekly at a dose of 56mg/m².

If you're receiving Kyprolis in combination with other anti-myeloma therapies, make sure you watch our other Know Your Therapy videos. The Kyprolis Patient Support program is designed to provide patients and caregivers with important information about Kyprolis, including educational materials that can help you follow your treatment plan. If you are a patient currently being treated with Kyprolis, you may also sign up to receive calls from an Amgen Nurse Navigator who can help provide the individualized support you need when you need

Call Amgen Assist 360 at 888-4ASSIST, Monday through Friday, 9 a.m. to 8 p.m. Eastern Time.

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