Suzierose,
Hope you are doing great.
Patients typically only take one IMID at a time. Although, Celgene Board Member Dr. Robert Orlowski has discussed combining Thalidomide and Revlimid in Revlimid refractorary patients to increase Celgene sales, I mean for the patients benefit. While Revlimid will not go off patent when pomalidomide is approved, it will increase the total amount of time Celgene has an IMID on patent, since there will be less overlap time between Revlimids patent time and Pomalidomides patent time. As I mentioned above, a patient can get access to pomalidomide, but they will most likely have to go to one of Celgene's biggest distributors - UAMS, Mayo, Dana-Farber, or MD Anderson to get it. As a side note, while Celgene is putting a Warning Label on Revlimid, the Doctors from the above Institutions seem (my observation) to go out of their way to encourage long term Revlimid use.
For selfish reasons, I would want Carfilzomib approved before pomalidomide. I have never used any IMID, while I have done 4 "double cycles" of Velcade as part of my Induction (2.6 mg/m2 on Days 1,4,8, 11 of a 3 week cycle - I was fortunate - no neuropathy!!!). I was still responding to Velcade when I stopped, but it may not work when I need to start therapy again. I would like for both to get approved "Pronto" for all my fellow patients.
In another thread that we were discussing Myeloma Stem Cells, I had mentioned that I had seen references to using the drug Fludarabine on Myeloma patients because it kills resting and active B Cells. I did ask my Doctor about this, since I used high dose Fludarabine at my Allo, and she did say that Fludarabine is primarily used for Allos to prevent rejection because it is so immunosuppressive, but she always uses Fludarabine at Allos for Myeloma patients because it does kill resting B Cells and that may be a part of the reason patients that do Allos in first remission have longer remissions than other patients. Obviously she gives the Donor Immune System the majority of the credit. Using Fludarabine as part of Induction is not feasible for patients that are planning to do Auto transplant because Fludarabine inhibits stem cell collection. It would seem the thought that Fludarabine may help increase patients PFS by killing a Myeloma Stem Cell would be very difficult to prove in practice.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222252/
Mark
Forums
Re: pomalidomide
HI Mark!
I have allergies and some pulmonary congestion but otherwise I am doing good. Thanks for asking. Hope you are doing well.
I was appalled at that alternating week dual IMID trial design at Mayo for the newly diagnosed!! The side effect profile alone with DVT's, myleosuppression, neuropathy &SPM??. Just unbelievable. Not to mention that as a single agent protesome inhibitors have better efficacy and side effects..even if Celgene doesn't manufacture one.
I hear you about Celgene's financial support stretching from academia to the FDA advisory panel. No doubt that a drug can have efficacy and safety but when there are issues surrounding either of the latter it is definitely worthwhile for a patient to pause and weigh the risks and benefits based on sources not likely due to the mfgr influence.
Less overlap time means fewer refractory/relapsed patients on IMIDs. i.e. decreased revenues. The total amount of time pomalidomide is on patent will be independent of when it is approved. Patent life can be extended by new indications but total time when approved is the same unless the drug has orphan status. Now, Celgene could outsmart themselves and safety data on SPM results in patients not being willing to take pomalidomide and so they wind up taking thalidomide since it doesn't have statistically significant data on SPM, yet. I am sure the finance folks have already calculated how they will make up the profit margin loss from thalidomide with the cost of pomalidomide. And it would not surprise me if all of sudden there was a shortage of thalidomide since it is generic.
It appears that one of the major reasons we are not seeing generic IMID competition is because of the strigent regulatory criteria the FDA has placed on Celgene when it comes to marketing the drug.The monthly surveys and registration with the company as well as continuous 6 month follow up surveys. When it comes to child bearing age females the liability risks would certainly have to be weighed, calculated in as cost before a 'generic' price could be set. That creates a real problem since it would be the newly diagnosed multiple myeloma patients eligible for generics and they are not a large group making it far less cost effective for a generic mfgr to risk marketing the drug.
The bigger challenge for Celgene is the refractory/relapsed patient population is the largest market share, ergo it behooves them to push it thru now rather than later, as lenalidomide and thalidomide sales will continue to drop. However, pomalidomide has demonstrated remarkable efficacy in the relapsed/refractory multiple myeloma patient. So the money pot is clear.
Recently, a light bulb came on as I realized that relapsed/refractory multiple myeloma patients will forever serve as the clinical trial populations unless there is a drug with sustainable duration that manages multiple myeloma. Our choices, sadly, are limited to being the guinea pig more often than not..but then I suppose that is better than being expired mice.
Regarding Fludarabine as consolidation therapy for multiple myeloma patients, it sounds promising, in that it is not a DNA damaging alklylator but rather it inhibits RNA transcription of rapidly proliferating B cells, and often is descriped as a DNA repair inhibitor. I prefer the former descriptor as it tells us why the clonal B cells will be diminished. The problem though, as always, is it is not selective for the cancerous cells. Which would put the patient at risk for the B cells they need. However, I wonder if post auto BSCT if the patient received Fludarabine, perhaps that would attack any residual disease B cell population and thus result in longer progression free survival. Based on your link fludarabine cannot be used for induction as it inhibits SC harvest. I wonder what happened to those patients who were unable to be harvested. ..geesh...
Mark, I am sure you know how blessed you are to have been one of the few to not only have survived an allo but to be doing well as well. Between the allo and fludarabine, I will pray you continue to have PFS and never need another agent...or...who knows one of those dendritic vaccines may be on the market having demonstrated that multiple myeloma can be chronic and manageable with a simple vaccine and you can skip protesome inhibitors
Question for you...when you heard the mortality stats on allo...what made you decide to take the leap.
I have always found that to have been a helluva courageous decision on your part.
I have allergies and some pulmonary congestion but otherwise I am doing good. Thanks for asking. Hope you are doing well.
I was appalled at that alternating week dual IMID trial design at Mayo for the newly diagnosed!! The side effect profile alone with DVT's, myleosuppression, neuropathy &SPM??. Just unbelievable. Not to mention that as a single agent protesome inhibitors have better efficacy and side effects..even if Celgene doesn't manufacture one.
I hear you about Celgene's financial support stretching from academia to the FDA advisory panel. No doubt that a drug can have efficacy and safety but when there are issues surrounding either of the latter it is definitely worthwhile for a patient to pause and weigh the risks and benefits based on sources not likely due to the mfgr influence.
Less overlap time means fewer refractory/relapsed patients on IMIDs. i.e. decreased revenues. The total amount of time pomalidomide is on patent will be independent of when it is approved. Patent life can be extended by new indications but total time when approved is the same unless the drug has orphan status. Now, Celgene could outsmart themselves and safety data on SPM results in patients not being willing to take pomalidomide and so they wind up taking thalidomide since it doesn't have statistically significant data on SPM, yet. I am sure the finance folks have already calculated how they will make up the profit margin loss from thalidomide with the cost of pomalidomide. And it would not surprise me if all of sudden there was a shortage of thalidomide since it is generic.
It appears that one of the major reasons we are not seeing generic IMID competition is because of the strigent regulatory criteria the FDA has placed on Celgene when it comes to marketing the drug.The monthly surveys and registration with the company as well as continuous 6 month follow up surveys. When it comes to child bearing age females the liability risks would certainly have to be weighed, calculated in as cost before a 'generic' price could be set. That creates a real problem since it would be the newly diagnosed multiple myeloma patients eligible for generics and they are not a large group making it far less cost effective for a generic mfgr to risk marketing the drug.
The bigger challenge for Celgene is the refractory/relapsed patient population is the largest market share, ergo it behooves them to push it thru now rather than later, as lenalidomide and thalidomide sales will continue to drop. However, pomalidomide has demonstrated remarkable efficacy in the relapsed/refractory multiple myeloma patient. So the money pot is clear.
Recently, a light bulb came on as I realized that relapsed/refractory multiple myeloma patients will forever serve as the clinical trial populations unless there is a drug with sustainable duration that manages multiple myeloma. Our choices, sadly, are limited to being the guinea pig more often than not..but then I suppose that is better than being expired mice.
Regarding Fludarabine as consolidation therapy for multiple myeloma patients, it sounds promising, in that it is not a DNA damaging alklylator but rather it inhibits RNA transcription of rapidly proliferating B cells, and often is descriped as a DNA repair inhibitor. I prefer the former descriptor as it tells us why the clonal B cells will be diminished. The problem though, as always, is it is not selective for the cancerous cells. Which would put the patient at risk for the B cells they need. However, I wonder if post auto BSCT if the patient received Fludarabine, perhaps that would attack any residual disease B cell population and thus result in longer progression free survival. Based on your link fludarabine cannot be used for induction as it inhibits SC harvest. I wonder what happened to those patients who were unable to be harvested. ..geesh...
Mark, I am sure you know how blessed you are to have been one of the few to not only have survived an allo but to be doing well as well. Between the allo and fludarabine, I will pray you continue to have PFS and never need another agent...or...who knows one of those dendritic vaccines may be on the market having demonstrated that multiple myeloma can be chronic and manageable with a simple vaccine and you can skip protesome inhibitors
Question for you...when you heard the mortality stats on allo...what made you decide to take the leap.
I have always found that to have been a helluva courageous decision on your part.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: pomalidomide
Suzierose,
I know I am fortunate to have had such a smooth Allo transplant. I am treated at a teaching Hospital and it is not uncommon for a Medical Student to speak with me first and then my Doctor comes in later for the visit and the Student observes. About 3 months after the Transplant my Doctor walked in and told the Student I was as good of an example as she would see of a patient that was "sailing right through the Allo process."
My presentation of Myeloma is considered high risk in the sense that it goes into remission quickly but the consensus of the 3 Doctors I had consultations with was that my remission would be expected to last 12-20 months in the non-Allo setting. The only one of the 3 that proposed the Allo upfront was the one I choose. Prior to this minor "Myeloma thing" I can only remember using Prescription drugs twice in my life. I used to joke that all the Big Pharmas would be small businesses if everyone was like me - how times have changed! The way Myeloma is treated by most Doctors is most unappealing to me. Never ending cycles of drugs/steroids and Myeloma Doctors do not even use Molecular or Immunophenotypic testing to check if the drugs/steroids are even killing any cancer cells.
I was diagnosed at Stage 3 with 3 compression fractures in my back. Since the first Doctor wanted to do the Allo early she had my Brother checked. He was not a match. As it turned out there was a matched donor in the BeTheMatch registry and it was a female. It is known that a female donor to a male recipient has the lowest chance of relapse in Allo transplantation but the highest chance of GVHD. I am not much of a fan of Auto transplants. As mentioned above, none of the Doctors thought it was likely to give me a long remission and high dose Melphalan is obviously not a good thing for a patient long term. My Doctors plan was to do Induction to remission and then go right to Allo. The other plans were basically use Drugs, do an Auto or 2, and hope a new therapy comes out and if not do an Allo later when it is has a much less chance of working and a much higher Non-Relapse Mortality related to the procedure. You could see where my Doctors treatment plan was so attractive to someone that hates taking Prescription drugs. Also, a matched donor may not always be available.
I ended up having to do an Auto prior to Allo because my Insurance company would not pay for Induction to Allo – only Tandem Auto- Allo. I also like my Doctors strategy with regard to Allo. Instead of Auto to lower Chemo intensity Allo, she looks at breaking up the intensity by using ATG to partially deplete the TCells. She uses a higher level of Chemo (Fludarabine/Melphalan) than most studies. As you can tell, she does not like to use the “cutting edge” strategy of high dose Melphalan over and over again. If needed afterward, she can use DLI’s to increase the amount of Immunotherapy. ATG prior to Allo has been shown to substantially decrease the chance of Extensive Chronic GVHD. ATG has anti-Myeloma activity also. Our 2 top Myeloma therapies fit in perfectly with the Allo process. If you Google “Bortezomib GVHD” you will see Bortezomib is being used in Clinical trials to treat patients with steroid refractory chronic GVHD and early in the Allo process to prevent GVHD in the first place. Small studies show Allo increases the efficiency of Revlimid as compared to the non-Allo setting.
http://ash.confex.com/ash/2011/webprogram/Paper43648.html
I knew I was taking a risk most patients do not take upfront, but I think Doctors are not honestly discussing with their patients the side effects of never ending cycles of Chemo/Novel Agents/Steroids. I guess it is “pick your poison” for Myeloma patients currently. Thank you for your prayers. I pray every patient makes the right choice for them and that a new therapy can turn this into a truly chronic disease with much less side effects than the current ones have. How special the people are that donate their stem cells. To donate their cells to a total stranger makes them great people in my mind.
Mark
I know I am fortunate to have had such a smooth Allo transplant. I am treated at a teaching Hospital and it is not uncommon for a Medical Student to speak with me first and then my Doctor comes in later for the visit and the Student observes. About 3 months after the Transplant my Doctor walked in and told the Student I was as good of an example as she would see of a patient that was "sailing right through the Allo process."
My presentation of Myeloma is considered high risk in the sense that it goes into remission quickly but the consensus of the 3 Doctors I had consultations with was that my remission would be expected to last 12-20 months in the non-Allo setting. The only one of the 3 that proposed the Allo upfront was the one I choose. Prior to this minor "Myeloma thing" I can only remember using Prescription drugs twice in my life. I used to joke that all the Big Pharmas would be small businesses if everyone was like me - how times have changed! The way Myeloma is treated by most Doctors is most unappealing to me. Never ending cycles of drugs/steroids and Myeloma Doctors do not even use Molecular or Immunophenotypic testing to check if the drugs/steroids are even killing any cancer cells.
I was diagnosed at Stage 3 with 3 compression fractures in my back. Since the first Doctor wanted to do the Allo early she had my Brother checked. He was not a match. As it turned out there was a matched donor in the BeTheMatch registry and it was a female. It is known that a female donor to a male recipient has the lowest chance of relapse in Allo transplantation but the highest chance of GVHD. I am not much of a fan of Auto transplants. As mentioned above, none of the Doctors thought it was likely to give me a long remission and high dose Melphalan is obviously not a good thing for a patient long term. My Doctors plan was to do Induction to remission and then go right to Allo. The other plans were basically use Drugs, do an Auto or 2, and hope a new therapy comes out and if not do an Allo later when it is has a much less chance of working and a much higher Non-Relapse Mortality related to the procedure. You could see where my Doctors treatment plan was so attractive to someone that hates taking Prescription drugs. Also, a matched donor may not always be available.
I ended up having to do an Auto prior to Allo because my Insurance company would not pay for Induction to Allo – only Tandem Auto- Allo. I also like my Doctors strategy with regard to Allo. Instead of Auto to lower Chemo intensity Allo, she looks at breaking up the intensity by using ATG to partially deplete the TCells. She uses a higher level of Chemo (Fludarabine/Melphalan) than most studies. As you can tell, she does not like to use the “cutting edge” strategy of high dose Melphalan over and over again. If needed afterward, she can use DLI’s to increase the amount of Immunotherapy. ATG prior to Allo has been shown to substantially decrease the chance of Extensive Chronic GVHD. ATG has anti-Myeloma activity also. Our 2 top Myeloma therapies fit in perfectly with the Allo process. If you Google “Bortezomib GVHD” you will see Bortezomib is being used in Clinical trials to treat patients with steroid refractory chronic GVHD and early in the Allo process to prevent GVHD in the first place. Small studies show Allo increases the efficiency of Revlimid as compared to the non-Allo setting.
http://ash.confex.com/ash/2011/webprogram/Paper43648.html
I knew I was taking a risk most patients do not take upfront, but I think Doctors are not honestly discussing with their patients the side effects of never ending cycles of Chemo/Novel Agents/Steroids. I guess it is “pick your poison” for Myeloma patients currently. Thank you for your prayers. I pray every patient makes the right choice for them and that a new therapy can turn this into a truly chronic disease with much less side effects than the current ones have. How special the people are that donate their stem cells. To donate their cells to a total stranger makes them great people in my mind.
Mark
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Mark
13 posts
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