"Adding the investigational protease inhibitor carfilzomib [Kyprolis] to lenalidomide and low-dose dexamethasone produced responses comparable with those achieved with the best front-line regimens in multiple myeloma, final results from a multicenter phase I/II study indicate.
Nearly all, 94%, of 49 evaluable patients with newly diagnosed multiple myeloma achieved at least a partial response with the triple combination, and 53% attained a near complete, complete or stringent complete response (nCR/CR/sCR).
Responses also continued to improve with time, with 79% of patients reaching a nCR/CR/sCR after 12 cycles, Dr. Andrzej J. Jakubowiak reported on behalf of the Multiple Myeloma Research Consortium. Although the data are still being evaluated, about half of the nCR/CR/sCRs were complete responses.
“These response rates appear to compare favorably to the best frontline regimens in myeloma and, I would dare to say, they compare favorably to treatment sequences with transplant,” said Dr. Jakubowiak, director of the multiple myeloma program at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
The combination of carfilzomib, lenalidomide (Revlimid), and dexamethasone previously posted an encouraging overall response rate of 78% and a nCR/CR rate of 40% with a low toxicity profile in the relapsed and/or refractory setting, providing the rationale for two ongoing phase III trials. The ASPIRE trial is evaluating lenalidomide and dexamethasone with or without carfilzomib in relapsed myeloma; the FOCUS trial, to support registration in Europe, is evaluating single-agent carfilzomib in relapsed/refractory myeloma.
Onyx Pharmaceuticals Inc. has announced that FDA is giving carfilzomib a standard review in the treatment of relapsed and refractory myeloma, with a decision expected by July 27."
http://www.oncologystat.com/news/Phase_II_Results_Continue_to_Support_Carfilzomib_in_Myeloma.html
Forums
Re: carfilzomib responses comparable to BST says Jakubowiak
I'm guessing this was probably based on Dr J's presentation at ASH this past December, or perhaps something he's presented since based on the same results. Being part of the CRD trial, I can attest to its effectiveness, having reached sCR after 11 cycles and knowing several other patients that have also reached CR and sCR. I was told the majority of patieints that reached CR also reached sCR.
Truly, this is a great response, and comparable to stem cell transplant. However, I wonder whether the depth of response will also translate into duration of response as well. My thinking goes like this...
With the CRD treatment, you are basically attacking the cancerous M-protein cells in your marrow and blood. This is good, since they're the buggers that cause all the damage. However, the stem cells that are producing the cancerous M-Proteins are not being attacked in the same way. Consequently, when treatment stops, the stem cells continue to produce the cancerous cells, and how long will it take before they reach critical mass again?
With a stem cell transplant, you also work to beat back the cancerous M-proteins, but then collect stems cells, take heavy-duty chemo to kill off the remaing stem cells, then reintroduce the collected stem cells. In this case, you've effectively killed off a bunch of the stem cells in addition to the M-proteins, and theoretically, the only cancerous stem cells should be those reintroduced into your system by the transplant. Consequently, it seems like it would take a lot longer to reach critical mass again.
One of the things on my myeloma to-do list is a bit of research into the progression free response of RVD and other combination treatments to see how they compare with stem cell transplants, then try and extrapolate this to CRD.
Truly, this is a great response, and comparable to stem cell transplant. However, I wonder whether the depth of response will also translate into duration of response as well. My thinking goes like this...
With the CRD treatment, you are basically attacking the cancerous M-protein cells in your marrow and blood. This is good, since they're the buggers that cause all the damage. However, the stem cells that are producing the cancerous M-Proteins are not being attacked in the same way. Consequently, when treatment stops, the stem cells continue to produce the cancerous cells, and how long will it take before they reach critical mass again?
With a stem cell transplant, you also work to beat back the cancerous M-proteins, but then collect stems cells, take heavy-duty chemo to kill off the remaing stem cells, then reintroduce the collected stem cells. In this case, you've effectively killed off a bunch of the stem cells in addition to the M-proteins, and theoretically, the only cancerous stem cells should be those reintroduced into your system by the transplant. Consequently, it seems like it would take a lot longer to reach critical mass again.
One of the things on my myeloma to-do list is a bit of research into the progression free response of RVD and other combination treatments to see how they compare with stem cell transplants, then try and extrapolate this to CRD.
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Kevin J - Name: Kevin J
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: Jan 2011
- Age at diagnosis: 52
Re: carfilzomib responses comparable to BST says Jakubowiak
I agree that that the issue of (the still to be identified) stem cells does pose a concern. But we should keep in mind that Revlimid (and maybe dex and zometa) alters the bone marrow environment, keeping it in a state that is hostile to cancer cell growth.
Hence combining new front-line therapy with proper maintenance -- and I would include nutrition and supplements in a maintenance regimen -- may be the way to go, rather than destroying your remaining healthy bone marrow.
For example, some "alternative" physicians urge the need to keep the bone marrow/blood./body in an alkaline state -- which supposedly freezes cancer in its tracks. It may be a coincidence, but I noticed that the pH of my urine was 5.5 when I was initially diagnosed with SMM - compared to neutral 18 months before. I also noticed that my calcium and vitamin D levels were below normal upon diagnosis -- compared to the proper range 18 months before. It is known that vitamin D and calcium act together to maintain cell-cell communication -- a process that is compromised by cancer. So trying to reset this balance may be a low-impact approach to maintenance (along with say low-dose Revlimid (or pomalidomide down the road)).
That said, I acknowledge that we just don't know enough about the newest modulators and whether they will obviate the need for ASCT. But what is clear is that an ASCT should always be approached with caution. Why does James Berenson, whose treatments offer among the longest and highest quality survival, absolutely counsel NOT to do it - unless as a last resort? He properly views this disease as a marathon, where chronic disease management should be a priority. We should all be looking more closely at his approach -- where less is more. .
that, in many cases, will have no or negligible benefit. To the contrary, we have read here of the myriad of long-term side-effects -- most recently sexual side effects -- and other problems resulting from stem cell transplants. This includes the disturbing finding that the "healthy" transplanted bone marrow may now be much more sensitive to chemotherapeutic agents, compromising treatment options upon relapse due to their heightened adverse effects on otherwise healthy cells.
But again,
In that regard, stem cell transplants increasingly strike me as a brutal, high-risk measure this disease is individualized. But for standard-risk patients, we should take comfort that this is a very slow-growing cancer, and we should not immediately jump on band-wagon therapies. It is easy -- and safe -- for an oncologist to recommend upfront agressive chemo and an immediate stem cell transplant. But would they recommend the same for themselves?
Hence combining new front-line therapy with proper maintenance -- and I would include nutrition and supplements in a maintenance regimen -- may be the way to go, rather than destroying your remaining healthy bone marrow.
For example, some "alternative" physicians urge the need to keep the bone marrow/blood./body in an alkaline state -- which supposedly freezes cancer in its tracks. It may be a coincidence, but I noticed that the pH of my urine was 5.5 when I was initially diagnosed with SMM - compared to neutral 18 months before. I also noticed that my calcium and vitamin D levels were below normal upon diagnosis -- compared to the proper range 18 months before. It is known that vitamin D and calcium act together to maintain cell-cell communication -- a process that is compromised by cancer. So trying to reset this balance may be a low-impact approach to maintenance (along with say low-dose Revlimid (or pomalidomide down the road)).
That said, I acknowledge that we just don't know enough about the newest modulators and whether they will obviate the need for ASCT. But what is clear is that an ASCT should always be approached with caution. Why does James Berenson, whose treatments offer among the longest and highest quality survival, absolutely counsel NOT to do it - unless as a last resort? He properly views this disease as a marathon, where chronic disease management should be a priority. We should all be looking more closely at his approach -- where less is more. .
that, in many cases, will have no or negligible benefit. To the contrary, we have read here of the myriad of long-term side-effects -- most recently sexual side effects -- and other problems resulting from stem cell transplants. This includes the disturbing finding that the "healthy" transplanted bone marrow may now be much more sensitive to chemotherapeutic agents, compromising treatment options upon relapse due to their heightened adverse effects on otherwise healthy cells.
But again,
In that regard, stem cell transplants increasingly strike me as a brutal, high-risk measure this disease is individualized. But for standard-risk patients, we should take comfort that this is a very slow-growing cancer, and we should not immediately jump on band-wagon therapies. It is easy -- and safe -- for an oncologist to recommend upfront agressive chemo and an immediate stem cell transplant. But would they recommend the same for themselves?
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Dan D
Typos Corrected: carfilzomib responses comparable to BST
Sorry: my last reply got jumbled.
I agree that that the issue of (the still to be identified) stem cells does pose a concern. But we should keep in mind that Revlimid (and maybe dex and zometa) alters the bone marrow environment, keeping it in a state that is hostile to cancer cell growth.
Hence combining new front-line therapy with proper maintenance -- and I would include nutrition and supplements in a maintenance regimen -- may be the way to go, rather than destroying your remaining healthy bone marrow.
For example, some "alternative" physicians urge the need to keep the bone marrow/blood./body in an alkaline state -- which supposedly freezes cancer in its tracks. It may be a coincidence, but I noticed that the pH of my urine was 5.5 when I was initially diagnosed with SMM - compared to neutral 18 months before. I also noticed that my calcium and vitamin D levels were below normal upon diagnosis -- compared to the proper range 18 months before. It is known that vitamin D and calcium act together to maintain cell-cell communication -- a process that is compromised by cancer. So trying to reset this balance may be a low-impact approach to maintenance (along with say low-dose Revlimid (or pomalidomide down the road)).
That said, I acknowledge that we just don't know enough about the newest modulators and whether they will obviate the need for ASCT. But what is clear is that an ASCT should always be approached with caution. Why does James Berenson, whose treatments offer among the longest and highest quality survival, absolutely counsel NOT to do it - unless as a last resort? He properly views this disease as a marathon, where chronic disease management should be a priority. We should all be looking more closely at his approach -- where less is more.
In this regard, stem cell transplants increasingly strike me as brutal, high risk measures that, in many cases, will have no or negligible benefit. To the contrary, we have read here of the myriad of long-term side-effects -- most recently sexual side effects -- and other problems resulting from stem cell transplants. This includes the disturbing finding that the "healthy" transplanted bone marrow may now be much more sensitive to chemotherapeutic agents, compromising treatment options upon relapse due to their heightened adverse effects on otherwise healthy cells.
Of course, this disease is individualized. But for standard-risk patients, we should take comfort that this is a very slow-growing cancer, and we should not immediately jump on band-wagon therapies. It is easy -- and safe -- for an oncologist to recommend upfront aggressive chemo and an immediate stem cell transplant. But would they recommend the same for themselves?
I agree that that the issue of (the still to be identified) stem cells does pose a concern. But we should keep in mind that Revlimid (and maybe dex and zometa) alters the bone marrow environment, keeping it in a state that is hostile to cancer cell growth.
Hence combining new front-line therapy with proper maintenance -- and I would include nutrition and supplements in a maintenance regimen -- may be the way to go, rather than destroying your remaining healthy bone marrow.
For example, some "alternative" physicians urge the need to keep the bone marrow/blood./body in an alkaline state -- which supposedly freezes cancer in its tracks. It may be a coincidence, but I noticed that the pH of my urine was 5.5 when I was initially diagnosed with SMM - compared to neutral 18 months before. I also noticed that my calcium and vitamin D levels were below normal upon diagnosis -- compared to the proper range 18 months before. It is known that vitamin D and calcium act together to maintain cell-cell communication -- a process that is compromised by cancer. So trying to reset this balance may be a low-impact approach to maintenance (along with say low-dose Revlimid (or pomalidomide down the road)).
That said, I acknowledge that we just don't know enough about the newest modulators and whether they will obviate the need for ASCT. But what is clear is that an ASCT should always be approached with caution. Why does James Berenson, whose treatments offer among the longest and highest quality survival, absolutely counsel NOT to do it - unless as a last resort? He properly views this disease as a marathon, where chronic disease management should be a priority. We should all be looking more closely at his approach -- where less is more.
In this regard, stem cell transplants increasingly strike me as brutal, high risk measures that, in many cases, will have no or negligible benefit. To the contrary, we have read here of the myriad of long-term side-effects -- most recently sexual side effects -- and other problems resulting from stem cell transplants. This includes the disturbing finding that the "healthy" transplanted bone marrow may now be much more sensitive to chemotherapeutic agents, compromising treatment options upon relapse due to their heightened adverse effects on otherwise healthy cells.
Of course, this disease is individualized. But for standard-risk patients, we should take comfort that this is a very slow-growing cancer, and we should not immediately jump on band-wagon therapies. It is easy -- and safe -- for an oncologist to recommend upfront aggressive chemo and an immediate stem cell transplant. But would they recommend the same for themselves?
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Dan D
Re: carfilzomib responses comparable to BST says Jakubowiak
It's great to hear that the carfilzomib trials are going so well! Congrats on your CR, Kevin! I wonder if the FDA would be asked to consider this drug for initially diagnosed as well as relapsed patients?
I suppose more studies need be done to determine whether or not stem cell transplants make for a longer good response to the drug. That seems to be a concern for the future of treatments.
Would carfilzomib be favored because of less of side effects, such as PN? It is another option, (at least for clinical trials) but how does it differ from Revlimid?
I suppose more studies need be done to determine whether or not stem cell transplants make for a longer good response to the drug. That seems to be a concern for the future of treatments.
Would carfilzomib be favored because of less of side effects, such as PN? It is another option, (at least for clinical trials) but how does it differ from Revlimid?
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: carfilzomib responses comparable to BST says Jakubowiak
I think I should have said...how does carfilzomib compare to Velcade?
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: carfilzomib responses comparable to BST says Jakubowiak
Hi Dan D,
I have read about Dr. Berenson and his approach. He is on the wrong coast for me. I was just wondering if you or anyone else knows of multiple myeloma experts on the East Coast who share a similar philsophy with regards to SCT's. It seems most multiple myeloma experts are transplanters by training, so who besides Berenson is an multiple myeloma expert and not a traditional transplanter. I already know Dr. Landgren. Anyone else? Thanks. Terry
I have read about Dr. Berenson and his approach. He is on the wrong coast for me. I was just wondering if you or anyone else knows of multiple myeloma experts on the East Coast who share a similar philsophy with regards to SCT's. It seems most multiple myeloma experts are transplanters by training, so who besides Berenson is an multiple myeloma expert and not a traditional transplanter. I already know Dr. Landgren. Anyone else? Thanks. Terry
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terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
Re: carfilzomib responses comparable to BST says Jakubowiak
Velcade and Carfilzomib are proteasome inhibitors. From my non-biological perspective, proteasomes are like the waste treatment process for cells. They breakdown damaged or unneeded proteins into amino acids that are used to synthesize new proteins. A proteasome inhibitor, like the name says, inhibits the proteasome process and causes the damaged and unneeded proteins to build up in the cell which eventually causes the cell to die.
Given results so far, Carfilzomib seems like it may be somewhat more effective than Velcade in attacking M-Proteins, and also appears not to attack healthy cells as much. In addition, Carfilzomib has also been engineered to reduce the severity of side effects - in particular, peripheral neuropathy appears to be much less than with Velcade.
Given results so far, Carfilzomib seems like it may be somewhat more effective than Velcade in attacking M-Proteins, and also appears not to attack healthy cells as much. In addition, Carfilzomib has also been engineered to reduce the severity of side effects - in particular, peripheral neuropathy appears to be much less than with Velcade.
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Kevin J - Name: Kevin J
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: Jan 2011
- Age at diagnosis: 52
Re: carfilzomib responses comparable to BST says Jakubowiak
Dan, do you have any links to information regarding pH level and cancer? This is something I was not familiar with. Like you, I'd like to keep the SCT as a later treatment and see if I can't manage this disease for a number of years by other means.
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Kevin J - Name: Kevin J
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: Jan 2011
- Age at diagnosis: 52
Re: carfilzomib responses comparable to BST says Jakubowiak
Regarding pH and cancer, I have to reemphasize that this is an “alternative” view – and not surprisingly, it is controversial. Indeed, many would say it has been debunked. See, e.g., the following: http://www.livestrong.com/article/494740-cancer-and-the-acid-balance-in-the-body/
But I am being a bit more open-minded. It is known that the growth of cancer cells in the laboratory is inhibited under alkaline conditions. And yes -- it is also known that the body has elaborate homeostatic mechanisms to maintain the blood pH in a slightly alkaline state (7.4).
In view of this homeostatic process, it has been argued that it would be nearly impossible to alter the pH of the blood. This may well be true. But I wonder whether this homeostatic mechanism ITSELF has been reset during cancer – and hence interventions to reestablish the appropriate balance might make sense. I also wonder why the blood pH is not part of the standard laboratory testing – given that urine pH is. Is it because blood pH is assumed to be at 7.4?
But despite this issue– there IS general agreement that nutrition does matter and that certain foods are certainly undesirable.
I would never argue that nutrition is curative. But I do not exclude the possibility – yet – that nutrition and supplements, in combination with other approaches, may help correct improper balances and perhaps keep the cancer under control.
There are certain blogs linked here – such as those of cancer girl – which refer to such alternative, “nutritional” approaches, in particular that of Dr. Gonzales in New York. This guy is no academic slouch – and his work and success is provocative and worthy of review. Check it out. http://www.dr-gonzalez.com/index.htm
But I am being a bit more open-minded. It is known that the growth of cancer cells in the laboratory is inhibited under alkaline conditions. And yes -- it is also known that the body has elaborate homeostatic mechanisms to maintain the blood pH in a slightly alkaline state (7.4).
In view of this homeostatic process, it has been argued that it would be nearly impossible to alter the pH of the blood. This may well be true. But I wonder whether this homeostatic mechanism ITSELF has been reset during cancer – and hence interventions to reestablish the appropriate balance might make sense. I also wonder why the blood pH is not part of the standard laboratory testing – given that urine pH is. Is it because blood pH is assumed to be at 7.4?
But despite this issue– there IS general agreement that nutrition does matter and that certain foods are certainly undesirable.
I would never argue that nutrition is curative. But I do not exclude the possibility – yet – that nutrition and supplements, in combination with other approaches, may help correct improper balances and perhaps keep the cancer under control.
There are certain blogs linked here – such as those of cancer girl – which refer to such alternative, “nutritional” approaches, in particular that of Dr. Gonzales in New York. This guy is no academic slouch – and his work and success is provocative and worthy of review. Check it out. http://www.dr-gonzalez.com/index.htm
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Dan D
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