I was taken by surprise by the article in the news section of The Beacon regarding the high percentage of test patients in the carfilzomib (Kyprolis) study experiencing heart issues.
It seems that carfilzomib has had better results than Velcade in studies and patients were not experiencing the peripheral nueropophy that many Velcade users suffer with. However, 25% having heart issues with carfilzomib, if true, is far too risky to be a drug that will be approved for wide use.
Some of the posters on this board have had great results with carfilzomib when combined with Revlimid and Dex.
I was sure hoping that this drug could be added to the mix exapecially for relapses and refractory patients that may be running out of options.
Ron
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: carfilzomib side effects
Hi Ron,
The same cardiac effects are seen with bortezomib
https://docs.google.com/viewer?a=v&q=cache:klvj2QxJbVMJ:www.cardiologyres.org/index.php/Cardiologyres/article/viewPDFInterstitial/5/7+proteasome+inhibitor+cardiac+effects&hl=en&gl=us&pid=bl&srcid=ADGEESir0j_R3kamLog-DO2Xn9bTTqbMLjAeX4jTI-la1o_JJdWa1Wzv4NKIBtbKHvRIhwxKgHk4TP-_1zqER1kvlErekwokpW-5x61Qfscng5vBMox8-UpQ9AcLd-Rp8CcE9lORKgDA&sig=AHIEtbTgUb_cW6DOsYWsmJ6_Q96ORJOfqw
And there was a thread on proteasome inhibitors and cardiac effects on the Beacon forum in April
https://myelomabeacon.org/forum/proteasome-inhibitors-and-the-cardiovascular-system-t986.html
The same cardiac effects are seen with bortezomib
https://docs.google.com/viewer?a=v&q=cache:klvj2QxJbVMJ:www.cardiologyres.org/index.php/Cardiologyres/article/viewPDFInterstitial/5/7+proteasome+inhibitor+cardiac+effects&hl=en&gl=us&pid=bl&srcid=ADGEESir0j_R3kamLog-DO2Xn9bTTqbMLjAeX4jTI-la1o_JJdWa1Wzv4NKIBtbKHvRIhwxKgHk4TP-_1zqER1kvlErekwokpW-5x61Qfscng5vBMox8-UpQ9AcLd-Rp8CcE9lORKgDA&sig=AHIEtbTgUb_cW6DOsYWsmJ6_Q96ORJOfqw
And there was a thread on proteasome inhibitors and cardiac effects on the Beacon forum in April
https://myelomabeacon.org/forum/proteasome-inhibitors-and-the-cardiovascular-system-t986.html
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: carfilzomib side effects
I have a couple of thoughts:
1) Many of the patients that have been treated with carfilzomib to date have fairly advanced, heavily pre-treated disease. As such, many of the participants in the original carfilzomib studies had dealt with numerous set backs from their myeloma and side effects of therapy for years prior to being exposed to the drug. The side effect profile of any drug in this situation can look bad.
2) Due to kidney issues in early studies, aggressive hydration around the time of carfilzomib infusion has been used to reduce this risk. So, if a patient has a history of heart failure (or low normal heart function) or atrial fibrillation and gets a lot of IV fluids (and has a tendency to retain that fluid due to concomitant use of dexamethasone), you can envision a scenario where you get exacerbation of heart failure and a predisposition to atrial fibrillation.
This is not to trivialize the risk. We have to be careful moving forward. The ASPIRE trial, a head-to-head study of Revlimid/dex vs. Revlimid/dex/carfilzomib will give us a better sense as to the level of increased cardiac risk with this agent. This study has finished enrolling patients.
As Suzierose has posted before, there is no free lunch with myeloma therapy and we always have to weigh the risks and benefits of any treatment. Until further studies emerge, physicians and patients will have to be highly vigilant and monitor for signs and symptoms of cardiac issues carefully.
On a positive note, ODAC reviewed carfilzomib favorably. They had the cardiac data in hand when that recommendation was made. As such, for this patient population, the advisory committee to the FDA felt that the benefits of carfilzomib outweigh the risks. At my institution. we have had patients with refractory disease derive great benefit from this drug.
And no, I do not receive funding from or own stock in Onyx.
I hope this helps!
Pete V.
1) Many of the patients that have been treated with carfilzomib to date have fairly advanced, heavily pre-treated disease. As such, many of the participants in the original carfilzomib studies had dealt with numerous set backs from their myeloma and side effects of therapy for years prior to being exposed to the drug. The side effect profile of any drug in this situation can look bad.
2) Due to kidney issues in early studies, aggressive hydration around the time of carfilzomib infusion has been used to reduce this risk. So, if a patient has a history of heart failure (or low normal heart function) or atrial fibrillation and gets a lot of IV fluids (and has a tendency to retain that fluid due to concomitant use of dexamethasone), you can envision a scenario where you get exacerbation of heart failure and a predisposition to atrial fibrillation.
This is not to trivialize the risk. We have to be careful moving forward. The ASPIRE trial, a head-to-head study of Revlimid/dex vs. Revlimid/dex/carfilzomib will give us a better sense as to the level of increased cardiac risk with this agent. This study has finished enrolling patients.
As Suzierose has posted before, there is no free lunch with myeloma therapy and we always have to weigh the risks and benefits of any treatment. Until further studies emerge, physicians and patients will have to be highly vigilant and monitor for signs and symptoms of cardiac issues carefully.
On a positive note, ODAC reviewed carfilzomib favorably. They had the cardiac data in hand when that recommendation was made. As such, for this patient population, the advisory committee to the FDA felt that the benefits of carfilzomib outweigh the risks. At my institution. we have had patients with refractory disease derive great benefit from this drug.
And no, I do not receive funding from or own stock in Onyx.
I hope this helps!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
Re: carfilzomib side effects
Dr. Voorhees,
thanks for the info. based on your experience, when do you think carfilzomib will be available to myeloma patients? I've been told about 4-6 weeks, assuming that FDA approves it on July 27th, 2012. thanks in advance for your response. Masood
thanks for the info. based on your experience, when do you think carfilzomib will be available to myeloma patients? I've been told about 4-6 weeks, assuming that FDA approves it on July 27th, 2012. thanks in advance for your response. Masood
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masood
Re: carfilzomib side effects
I think what you have been told should be accurate. Let's all cross our collective fingers...
Good luck!
Pete V.
Good luck!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
5 posts
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