My mother has just started therapy with carfilzomib [Kyprolis]as a single agent, as she is refractory to both Rev/Dex and Velcade/Dex. I understand that single agent Carfilzomib has a fairly low response rate in patients that have become resistant to Velcade, but that a recent ASH presentation from Dr. Berenson reveals that response rates are significantly higher when Carfilzomib is used in combination with other myeloma drugs. I asked Mom's oncologist whether he planned to try other drugs in combination with Carfilzomib if it does not produce a response as a single agent, and he basically told me "no", stating that it has not been tested in multi-drug combinations. He said the next step would probably be a melphalan based regimen. (Sadly, her Dr. is not very open to discussions regarding treatment)
Following are questions/concerns that I'm hoping someone can address:
1.) Does Carfilzomib have to be used as a single agent (because it was used as a single agent in clinical trials used to obtain FDA approval) unless the patient is currently enrolled in a clinical trial?
2.) How can I request that my mother's oncologist consult with a Myeloma Specialist? Are most oncologists willing to do this? (Traveling to a specialist for treatment is unfortunately not an option for my mother.)
3.) I know that treatment with a melphalan based regimen is not as harsh as the high dose melphalan administered prior to asct, but I'm still concerned that melphalan is not a good choice for someone who already exhibits cytogenetic instability [del 13, t(4;14)] ... Suzierose, if you read this, I'd appreciate any input you can provide!!!
Many thanks and blessings to you all!
Lisa B.
Forums
8 posts
• Page 1 of 1
-
Lisa B. - Name: Lisa B.
- Who do you know with myeloma?: My mother, Barbara Henson
- When were you/they diagnosed?: 10-28-11
- Age at diagnosis: 71
Re: Kyprolis (carfilzomib) single agent vs. multi-drug combo
Hi Lisa,
I can't comment on the "legalities" of using other drugs with carfilzomib but I can tell you my dad's experience. He is also high-risk, del 17. Refractory to Velcade and Revlimid. He is on his 4th cycle of carfilzomib / Cytoxan / dex and now thalidomide has been added.
His doctor started him on just carfilzomib/dex for about one month and then added the cytoxan.
I attended an multiple myeloma meeting with a Medical Liaison from Onyx to talk about carfilzomib and she said that nationally doctors are pairing carfilzomib with many of the established medications and that adding other treatments to the carfilzomib enahances the effacacy.
My dad's m-spike slowly climbed even after 3 cycles of the carfilzomib treatment. We waited until 4 full cycles and it finally dropped by a tenth of a point. Not much, but we are sticking with it a little longer.
As for alternative treatments, bendamustine was one that was mentioned by my dad's oncologist and we personally know another high-risk multiple myeloma patient who went into a complete response after 6 months of bendamustine treatment and he tolerated it well. I have heard similar reports from others. The problem is it is not intended to be a long term treatment; it seems 6 months or so is average.
I wish your mom the very best. Feel free to mail me personally if you want more info.
Dana
I can't comment on the "legalities" of using other drugs with carfilzomib but I can tell you my dad's experience. He is also high-risk, del 17. Refractory to Velcade and Revlimid. He is on his 4th cycle of carfilzomib / Cytoxan / dex and now thalidomide has been added.
His doctor started him on just carfilzomib/dex for about one month and then added the cytoxan.
I attended an multiple myeloma meeting with a Medical Liaison from Onyx to talk about carfilzomib and she said that nationally doctors are pairing carfilzomib with many of the established medications and that adding other treatments to the carfilzomib enahances the effacacy.
My dad's m-spike slowly climbed even after 3 cycles of the carfilzomib treatment. We waited until 4 full cycles and it finally dropped by a tenth of a point. Not much, but we are sticking with it a little longer.
As for alternative treatments, bendamustine was one that was mentioned by my dad's oncologist and we personally know another high-risk multiple myeloma patient who went into a complete response after 6 months of bendamustine treatment and he tolerated it well. I have heard similar reports from others. The problem is it is not intended to be a long term treatment; it seems 6 months or so is average.
I wish your mom the very best. Feel free to mail me personally if you want more info.
Dana
Re: Kyprolis (carfilzomib) single agent vs. multi-drug combo
Hi LisaB!
Your physician is completely in error regarding combining carfilzomib with other agents.
You may wish to refer him to this study present in 2011 at ASH https://ash.confex.com/ash/2011/webprogram/Paper39029.html
The other thing you may wish to convey is that carfilzomib is a protesome inhibitor just like bortezomib which has been used in numerous multi-drug combinations. Perhaps, he is unaware (more likely uninformed) of how this therapeutic class, proteasome inhibitors, has many successful in combination therapy.
Here are 2 of the most foremost experts addressing use of carfilzomib in patients refractory to bortezomib:
http://www.onclive.com/publications/obtn/2012/july-2012/Carfilzomib-Shows-Promise-as-Alternative-to-Bortezomib-in-Multiple-Myeloma
http://www.onclive.com/onclive-tv/Dr-Siegel-on-Carfilzomib-study
You may also wish to refer him to the CYCLONE study presented yesterday at ASH 2012:
https://ash.confex.com/ash/2012/webprogram/Paper52680.html
It is a newly diagnosed patient population, but his issue was drug combinations with carfilzomib.
You may wish to have him consult with Robert Orlowski at MD Anderson or Jakubowiak at U of Chicago both of whom have extensive experience in using carfilzomib in combination with other agents as well as in refractory patients.
There is also a combination with melphan which was presented at ASCO this summer by Dr. Moreau (France)as you mentioned...The goal of the French study was to determine the maximum tolerated dose of carfilzomib when used in combination with melphalan and prednisone in elderly myeloma patients.
Twenty-four myeloma patients were enrolled in the Phase 1 portion of the clinical trial.
Patients were randomly assigned to receive one of four different carfilzomib doses: 20 mg/m2, 27 mg/m2, 36 mg/m2, or 45 mg/m2 of carfilzomib administered intravenously on days 1, 2, 8, 9, 22, 23, 29, and 30 for nine 42-day cycles. In addition, all patients received 9 mg/m2 of oral melphalan and 60 mg/m2 of prednisone on days 1 to 4 of each cycle.
The researchers observed dose-limiting toxicities in two patients who received 45 mg/m2 of carfilzomib. A dose-limiting toxicity was defined as a severe blood toxicity that prevented the patient from receiving carfilzomib on at least two days during the first treatment cycle. The researchers therefore concluded that the maximum tolerated dose of carfilzomib was 36 mg/m2.
and here is what Orlowski says about it:
Dr. Orlowski, “Certainly, it looks like carfilzomib-melphalan-prednisone should prove to be a better tolerated regimen from the perspective of neuropathy.” In the Phase 1/2 study of Velcade-melphalan-prednisone, conducted a number of years ago, 17 percent of patients developed peripheral neuropathy.
Lastly, here are results of a study specific to your mom's disease/response profile:
"The analysis showed that single-agent carfilzomib demonstrated “clinically meaningful, durable responses” in patients who had advanced multiple myeloma.
The original study included a total of 266 relapsed or refractory myeloma patients. The researchers then analyzed the outcomes of specific patients within the study who had advanced disease.
In particular, they analyzed outcomes of 228 patients (86 percent) who were either intolerant or refractory (resistant) to Velcade as well as Revlimid or thalidomide (referred to as “double refractory/intolerant”).
They also analyzed outcomes of a subgroup of 44 patients (17 percent) who were refractory to all classes of myeloma treatments. This includes alkylators such as melphalan, anthracyclines such as doxorubicin (Adriamycin), corticosteroids such as dexamethasone, immunomodulatory agents such as Revlimid and thalidomide, and proteasome inhibitors such as Velcade.
Across all patients in the study, the median time since diagnosis was 5.4 years.
The results show that patients refractory to prior myeloma therapies had responses similar to the entire group of patients included in the study.
Specifically, overall response rates were 23 percent overall, 21 percent for those who were double refractory/intolerant, and 20 percent for those refractory to all classes of myeloma therapies.
Responses lasted 7.8 months for the entire study group, 7.4 months for the double refractory/intolerant group, and 7.8 months for those refractory to all classes of treatment."
You asked:
1.) Does carfilzomib have to be used as a single agent (because it was used as a single agent in clinical trials used to obtain FDA approval) unless the patient is currently enrolled in a clinical trial?
No, medical doctors are free to use any FDA approved drug however they decide is therapeutically best in a treatment regimen. The trial data gives demonstrated efficacy and many clinicians feel better using the drug as it was demonstrated to work in the clinical trial. However, it is solely their professional judgment as to how they will therapeutically use an agent that has demonstrated efficacy in a specific disease...often times they will even try the drug in a disease state that was not part of a clinical trial.
2.) How can I request that my mother's oncologist consult with a Myeloma Specialist? Are most oncologists willing to do this? (Traveling to a specialist for treatment is unfortunately not an option for my mother.)
This will be purely a matter of ego. Select a physician who is responsive to your wishes as a patient (mom) and it should not be an issue, unless it is about payment. After all, if he is consulting with a specialist, he is taking time away from the specialist seeing patients and there would likely need to be re-imbursement for that expertise.
You write:
I know that treatment with a melphalan based regimen is not as harsh as the high dose melphalan administered prior to asct, but I'm still concerned that melphalan is not a good choice for someone who already exhibits cytogenetic instability [del 13, t(4;14)] ... Suzierose, if you read this, I'd appreciate any input you can provide!!!
What you have surmised is correct. Melphalan is an alkylator and patients with abnormal chromosomes likely experience even more DNA instability when given melphalan at high doses. I suspect that lower doses would mean the impact would not be as great and would likely occur over a more extended period of time, given the reduced doses. The MOA of the drug remains the same however.
Also be sure to inquire about the dose he is using of carfilzomib...the 36mg/m works better than the 20mg/m and generally is tolerated due to lower toxicity profile than bortezomib.
Tell your mom I said hello...and be consistently persistent as her patient advocate and she will do well!!
Your physician is completely in error regarding combining carfilzomib with other agents.
You may wish to refer him to this study present in 2011 at ASH https://ash.confex.com/ash/2011/webprogram/Paper39029.html
The other thing you may wish to convey is that carfilzomib is a protesome inhibitor just like bortezomib which has been used in numerous multi-drug combinations. Perhaps, he is unaware (more likely uninformed) of how this therapeutic class, proteasome inhibitors, has many successful in combination therapy.
Here are 2 of the most foremost experts addressing use of carfilzomib in patients refractory to bortezomib:
http://www.onclive.com/publications/obtn/2012/july-2012/Carfilzomib-Shows-Promise-as-Alternative-to-Bortezomib-in-Multiple-Myeloma
http://www.onclive.com/onclive-tv/Dr-Siegel-on-Carfilzomib-study
You may also wish to refer him to the CYCLONE study presented yesterday at ASH 2012:
https://ash.confex.com/ash/2012/webprogram/Paper52680.html
It is a newly diagnosed patient population, but his issue was drug combinations with carfilzomib.
You may wish to have him consult with Robert Orlowski at MD Anderson or Jakubowiak at U of Chicago both of whom have extensive experience in using carfilzomib in combination with other agents as well as in refractory patients.
There is also a combination with melphan which was presented at ASCO this summer by Dr. Moreau (France)as you mentioned...The goal of the French study was to determine the maximum tolerated dose of carfilzomib when used in combination with melphalan and prednisone in elderly myeloma patients.
Twenty-four myeloma patients were enrolled in the Phase 1 portion of the clinical trial.
Patients were randomly assigned to receive one of four different carfilzomib doses: 20 mg/m2, 27 mg/m2, 36 mg/m2, or 45 mg/m2 of carfilzomib administered intravenously on days 1, 2, 8, 9, 22, 23, 29, and 30 for nine 42-day cycles. In addition, all patients received 9 mg/m2 of oral melphalan and 60 mg/m2 of prednisone on days 1 to 4 of each cycle.
The researchers observed dose-limiting toxicities in two patients who received 45 mg/m2 of carfilzomib. A dose-limiting toxicity was defined as a severe blood toxicity that prevented the patient from receiving carfilzomib on at least two days during the first treatment cycle. The researchers therefore concluded that the maximum tolerated dose of carfilzomib was 36 mg/m2.
and here is what Orlowski says about it:
Dr. Orlowski, “Certainly, it looks like carfilzomib-melphalan-prednisone should prove to be a better tolerated regimen from the perspective of neuropathy.” In the Phase 1/2 study of Velcade-melphalan-prednisone, conducted a number of years ago, 17 percent of patients developed peripheral neuropathy.
Lastly, here are results of a study specific to your mom's disease/response profile:
"The analysis showed that single-agent carfilzomib demonstrated “clinically meaningful, durable responses” in patients who had advanced multiple myeloma.
The original study included a total of 266 relapsed or refractory myeloma patients. The researchers then analyzed the outcomes of specific patients within the study who had advanced disease.
In particular, they analyzed outcomes of 228 patients (86 percent) who were either intolerant or refractory (resistant) to Velcade as well as Revlimid or thalidomide (referred to as “double refractory/intolerant”).
They also analyzed outcomes of a subgroup of 44 patients (17 percent) who were refractory to all classes of myeloma treatments. This includes alkylators such as melphalan, anthracyclines such as doxorubicin (Adriamycin), corticosteroids such as dexamethasone, immunomodulatory agents such as Revlimid and thalidomide, and proteasome inhibitors such as Velcade.
Across all patients in the study, the median time since diagnosis was 5.4 years.
The results show that patients refractory to prior myeloma therapies had responses similar to the entire group of patients included in the study.
Specifically, overall response rates were 23 percent overall, 21 percent for those who were double refractory/intolerant, and 20 percent for those refractory to all classes of myeloma therapies.
Responses lasted 7.8 months for the entire study group, 7.4 months for the double refractory/intolerant group, and 7.8 months for those refractory to all classes of treatment."
You asked:
1.) Does carfilzomib have to be used as a single agent (because it was used as a single agent in clinical trials used to obtain FDA approval) unless the patient is currently enrolled in a clinical trial?
No, medical doctors are free to use any FDA approved drug however they decide is therapeutically best in a treatment regimen. The trial data gives demonstrated efficacy and many clinicians feel better using the drug as it was demonstrated to work in the clinical trial. However, it is solely their professional judgment as to how they will therapeutically use an agent that has demonstrated efficacy in a specific disease...often times they will even try the drug in a disease state that was not part of a clinical trial.
2.) How can I request that my mother's oncologist consult with a Myeloma Specialist? Are most oncologists willing to do this? (Traveling to a specialist for treatment is unfortunately not an option for my mother.)
This will be purely a matter of ego. Select a physician who is responsive to your wishes as a patient (mom) and it should not be an issue, unless it is about payment. After all, if he is consulting with a specialist, he is taking time away from the specialist seeing patients and there would likely need to be re-imbursement for that expertise.
You write:
I know that treatment with a melphalan based regimen is not as harsh as the high dose melphalan administered prior to asct, but I'm still concerned that melphalan is not a good choice for someone who already exhibits cytogenetic instability [del 13, t(4;14)] ... Suzierose, if you read this, I'd appreciate any input you can provide!!!
What you have surmised is correct. Melphalan is an alkylator and patients with abnormal chromosomes likely experience even more DNA instability when given melphalan at high doses. I suspect that lower doses would mean the impact would not be as great and would likely occur over a more extended period of time, given the reduced doses. The MOA of the drug remains the same however.
Also be sure to inquire about the dose he is using of carfilzomib...the 36mg/m works better than the 20mg/m and generally is tolerated due to lower toxicity profile than bortezomib.
Tell your mom I said hello...and be consistently persistent as her patient advocate and she will do well!!
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Kyprolis (carfilzomib) single agent vs. multi-drug combo
Wow. Nice work Suzie. I'll refer back to this post before my next visit. Thanks. Stann
-
Stann
Re: Kyprolis (carfilzomib) Single Agent vs. Multi-Drug Combo
LisaB,
Here are the results from CYCLONE that were presented at ASCO this summer for your doc.
http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Clin%20Onc%20June%202012/Myeloma/Capsules/8010.aspx
The other link is more recent as it was yesterday's presentation at ASH, however, it's an abstract whereas the link above gives more data and background on the trial.
P.S. hehehehe, I just thought of something, you might just want to refer him to the Myeloma Beacon, and he can ask his questions in the forum, just like everyone else...
Here are the results from CYCLONE that were presented at ASCO this summer for your doc.
http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Clin%20Onc%20June%202012/Myeloma/Capsules/8010.aspx
The other link is more recent as it was yesterday's presentation at ASH, however, it's an abstract whereas the link above gives more data and background on the trial.
P.S. hehehehe, I just thought of something, you might just want to refer him to the Myeloma Beacon, and he can ask his questions in the forum, just like everyone else...
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Kyprolis (carfilzomib) single agent vs. multi-drug combo
MANY THANKS, Suzierose, for taking time to send all the helpful information!!!!! I appreciate it more than you can imagine!
... and as for your last post ... I wish he would!!!!!
I'll be the first to admit that I don't know nearly as much as he does about oncology, but it really bothers me that he seems to just "dismiss" everything I want to discuss. The problem is that Mom is not willing to travel for treatment, and her oncologist is the only one close by.
Thanks again for responding, and Mom and I continue to wish the very best for you!!
Lisa B.
... and as for your last post ... I wish he would!!!!!
I'll be the first to admit that I don't know nearly as much as he does about oncology, but it really bothers me that he seems to just "dismiss" everything I want to discuss. The problem is that Mom is not willing to travel for treatment, and her oncologist is the only one close by.Thanks again for responding, and Mom and I continue to wish the very best for you!!
Lisa B.
-
Lisa B. - Name: Lisa B.
- Who do you know with myeloma?: My mother, Barbara Henson
- When were you/they diagnosed?: 10-28-11
- Age at diagnosis: 71
Re: Kyprolis (carfilzomib) single agent vs. multi-drug comb
I usually start with carfilzomib and 20 mg of dexamethasone on day of carfilzomib. Responses can take 2-3 months to show up so, in the absence of increase in M-protein, I continue for that duration without adding 3rd drug. If 3rd drug is needed, it depends on prior therapy as to what I use.
In response to other posts, I agree that bendamustine can be effective as an option and reasonably well tolerated.
In response to other posts, I agree that bendamustine can be effective as an option and reasonably well tolerated.
-
Dr. Jason Valent - Name: Jason Valent, M.D.
Beacon Medical Advisor
Re: Kyprolis (carfilzomib) single agent vs. multi-drug combo
i am finished my first cycle of Kyprolis with cytoxan and dex.my flc`s numbers and creatatine are going up not down.should i continue with this prtocol or switch
thanks
AL
thanks
AL
8 posts
• Page 1 of 1
Return to Treatments & Side Effects