Multibilly!
O wow! your cytogenetics are good ...that is awesome!!!
Your choices are unlimited...great news.
I also found some more info on PN with bortezomib, just as an FYI for you:
"PN is frequently reported with bortezomib therapy.[6,26] In a pooled analysis of 256 patients with R/R multiple myeloma enrolled in the phase II SUMMIT and CREST trials of bortezomib, treatment-emergent PN occurred in 35% of patients overall, including 13% with grade 3 PN and 0.4% with grade 4 PN.[31] Dose reductions were necessary in 12% of patients, and 5% of patients discontinued therapy because of PN.[31] The clinical profile of bortezomib-induced PN includes neuropathic pain, mainly in the fingertips and toes, which may severely affect normal daily activities.[26,27] The risk of PN reaches a plateau by cycle 5, suggesting a dose threshold rather than a cumulative dose effect.[26,27] It improves or resolves in most patients at a median of 3 months after treatment is discontinued, but it has been reported that resolution can take as long as 2 years after treatment discontinuation.[27] Recent reports have indicated reduction in neuropathy with once-weekly dosing schedules and with subcutaneous administration.[32-34] Grade 1–3 bortezomib-induced motor neuropathy (involving distal weakness in the lower limbs) affects approximately 10% of patients.[26] Isolated cases of life-threatening grade 4 motor neurotoxicity have also been reported.[35]
The true incidence of bortezomib-induced autonomic neuropathy is not known. The fact that both constipation and diarrhea are associated with bortezomib in clinical trials may be relevant.[36] In a phase II study in patients with metastatic neuroendocrine tumors receiving a higher dose of bortezomib than the currently approved dose for multiple myeloma, 6 of 10 patients with PN also had symptoms such as grade 2/3 dizziness, orthostatic hypotension, syncope, ileus, and abdominal cramps.[37] Pooled data from the phase II SUMMIT and CREST studies of bortezomib in patients with R/R multiple myeloma revealed orthostatic hypotension in 12% of bortezomib-treated patients (grade 3 in 4% of patients).[26]
Two cases of grade 4 suspected autonomic neuropathy in patients with R/R multiple myeloma receiving bortezomib included reports of abdominal numbness, distension, and urinary retention in one patient and persistent diarrhea, despite antibiotics and antimotility medication, in another patient.[35] Two additional patients with PN during bortezomib treatment were reported to have developed paralytic ileus, urinary retention, and impotence.[35] A case of complete heart block believed to be directly related to bortezomib was recently reported in a patient with multiple myeloma.[36] Several of these patients had previously been exposed to other neurotoxic agents (thalidomide and vincristine) and had comorbid conditions associated with neurologic damage.[35]"
http://www.cancernetwork.com/supplements/onc-nov-2011/content/article/10165/1983635
I mentioned L-carnitine to you...if you do go with bortezomib...start taking it now..don't wait for it to appear...do preventive pro-active care,no harm in taking...L-carnitine.
While PN can be an issue...remember..you will get a far superior and deeper response with carfilzomib (better efficacy)...so also know that. Side effects are one issue, but best therapeutic response is even more important and you get that with carfilzomib. Since cytogenetics are not an issue..you have the best profile to get the best results of carfilzomib over bortezomib.
BTW, Here is the most recent study from ASH 2012 on carfilzomib...just in case you could need it.
I would substitute lenalidomide for thalidomide, cause of better tolerability. And I recommend 36mg/m2 of carfilzomib over the 20mg/m2 ...as a new patient you want the highest dose since it is tolerability and gives a greater depth of response. BTW, they are now using 56mg/m2 in clinical trials but 36mg/m2 works far better than the 20mg/m2
http://www.clinicaloptions.com/Oncology/Conference%20Coverage/Hematology%202012/Myeloma/Capsules/333.aspx
ETA: link
Choose wisely.
Forums
Re: Looking for Feedback on Recommended First Round Treatmen
Hi Multibilly,
It is fantastic news that your cytogenetics are good - that gives you many treatment options. No doubt there will be many more in the coming years as more novel agents are synthesised.
Peripheral neuropathy can be a pain in the proverbial if you can avoid it by choosing a chemotherapy agent that is less likely to cause it - I'd go for it. I stopped taking Velcade (it had stopped working - after 3 cycles) before the pn in my fingers became permanent but my feet are not good.
My myeloma was/is chemorefractory - I had my auto SCT in the hope that the melphalan would kill the myeloma but it didn't and it damn near killed the rest of me. My advice to anyone who is thinking about an auto is to think about what it will achieve and are there any other methods available that will do the same thing with less risk. I believe that there will always be a trade-off with any of the treatments we choose - it is making sure that the risk associated with each is minimized.
At present I am in a good place with regards to my myeloma. I am in remission now solely due to the graft vs myeloma effect of my allo transplant (and long may I stay there). If I had my myeloma journey again I would definitely skip the auto.
Does anyone know if L-carnitine has an effect on established pn?
Libby
It is fantastic news that your cytogenetics are good - that gives you many treatment options. No doubt there will be many more in the coming years as more novel agents are synthesised.
Peripheral neuropathy can be a pain in the proverbial if you can avoid it by choosing a chemotherapy agent that is less likely to cause it - I'd go for it. I stopped taking Velcade (it had stopped working - after 3 cycles) before the pn in my fingers became permanent but my feet are not good.
My myeloma was/is chemorefractory - I had my auto SCT in the hope that the melphalan would kill the myeloma but it didn't and it damn near killed the rest of me. My advice to anyone who is thinking about an auto is to think about what it will achieve and are there any other methods available that will do the same thing with less risk. I believe that there will always be a trade-off with any of the treatments we choose - it is making sure that the risk associated with each is minimized.
At present I am in a good place with regards to my myeloma. I am in remission now solely due to the graft vs myeloma effect of my allo transplant (and long may I stay there). If I had my myeloma journey again I would definitely skip the auto.
Does anyone know if L-carnitine has an effect on established pn?
Libby
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LibbyC - Name: LibbyC
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 2009
- Age at diagnosis: 43
Re: Looking for Feedback on Recommended First Round Treatmen
Right now, unless you are in a clinical trial, carfilzomib will not be available to you unless you are relapse or refractory. Velcade can be given to newely diagnosed patients as a front line therapy. Eventually Carilzomib will be allowed as a front line therapy but that could be a few years out. The good news is that those that use Velcade, like me, once they relapse have a new option. Options are always good!
Ron
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: Looking for Feedback on Recommended First Round Treatmen
Ron Harvot wrote:
> Right now, unless you are in a clinical trial, carfilzomib will not be
> available to you unless you are relapse or refractory. Velcade can be given
> to newely diagnosed patients as a front line therapy. Eventually
> Carilzomib will be allowed as a front line therapy but that could be a few
> years out. The good news is that those that use Velcade, like me, once
> they relapse have a new option. Options are always good!
>
> Ron
I became aware of that conditional approval as I researched this more. I am curious just how restrictive the FDA ruling truly is in practice based on the Myelomabeacon article below.
https://myelomabeacon.org/news/2012/08/17/kyprolis-carfilzomib-which-multiple-myeloma-patients-will-physicians-treat-with-it/
"...Although Kyprolis has been approved by the FDA for this specific set of myeloma patients, once a drug is approved in the U.S., physicians have substantial freedom to prescribe the drug as they deem appropriate.
At the same time, Medicare, Medicaid, and private insurance companies may decide to control health care costs by restricting reimbursement of Kyprolis treatment to patients meeting the FDA criteria described above. This may particularly be the case with Kyprolis, given that it is currently the most expensive myeloma treatment available."
> Right now, unless you are in a clinical trial, carfilzomib will not be
> available to you unless you are relapse or refractory. Velcade can be given
> to newely diagnosed patients as a front line therapy. Eventually
> Carilzomib will be allowed as a front line therapy but that could be a few
> years out. The good news is that those that use Velcade, like me, once
> they relapse have a new option. Options are always good!
>
> Ron
I became aware of that conditional approval as I researched this more. I am curious just how restrictive the FDA ruling truly is in practice based on the Myelomabeacon article below.
https://myelomabeacon.org/news/2012/08/17/kyprolis-carfilzomib-which-multiple-myeloma-patients-will-physicians-treat-with-it/
"...Although Kyprolis has been approved by the FDA for this specific set of myeloma patients, once a drug is approved in the U.S., physicians have substantial freedom to prescribe the drug as they deem appropriate.
At the same time, Medicare, Medicaid, and private insurance companies may decide to control health care costs by restricting reimbursement of Kyprolis treatment to patients meeting the FDA criteria described above. This may particularly be the case with Kyprolis, given that it is currently the most expensive myeloma treatment available."
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Looking for Feedback on Recommended First Round Treatmen
Hi Multibilly,
Sorry to see that you have joined the club. It seems like you were diagnosed fairly recently. Quite a bit of info was thrown at you in this thread. A lot of the posters in the thread have used a proteasome inhibitor (bortezomib or carfilzomib) combined with an IMID (Revlimid is most common, thalidomide and pomalidomide are also in this class of drug) and DEX (a steriod, another steroid less commonly used is prednisone). An auto transplant is a high dose of melphalan. Melphalan is in a class of drugs called alkylators. The other alkylators we typically use in myeloma are Cytoxan and bendumustine. There is one other class of drugs that I used that is not commonly used called these days called anthracyclines. I used a drug in that class called Doxil during my induction and it worked well with Velcade and DEX for me.
Many of the previous posters in this thread have used very long cycles of proteasome inhibitor/IMID and steroid. That is generally considered the most active combination but IMO it is a very risky strategy. Here is why. A recent study showed the outcomes for patients that are relapsed and are not responding to these drugs:
"Promising new drugs are being evaluated for treatment of multiple myeloma (multiple myeloma), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed multiple myeloma, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years, and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0–8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including partial response in 69 (32%). The median overall survival and event-free survival from T0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs."
http://www.nature.com/leu/journal/v26/n1/full/leu2011196a.html
A whole 9 months of overall survival once you become refractory to these classes of drugs. Long cycles of them can get you resistant to them earlier in disease course. The reality is that the Doctors that are prescribing this type of therapy have no good therapy to use once the patients stop responding to IMIDs and proteasome inhibitors. It is easy to just prescribe the 2 best classes of drugs to their patients as soon as they are diagnosed. A skilled Doctor has a strategy to keep thier patients from becoming resistant to these 2 classes of drugs in the first place.
Mark
Sorry to see that you have joined the club. It seems like you were diagnosed fairly recently. Quite a bit of info was thrown at you in this thread. A lot of the posters in the thread have used a proteasome inhibitor (bortezomib or carfilzomib) combined with an IMID (Revlimid is most common, thalidomide and pomalidomide are also in this class of drug) and DEX (a steriod, another steroid less commonly used is prednisone). An auto transplant is a high dose of melphalan. Melphalan is in a class of drugs called alkylators. The other alkylators we typically use in myeloma are Cytoxan and bendumustine. There is one other class of drugs that I used that is not commonly used called these days called anthracyclines. I used a drug in that class called Doxil during my induction and it worked well with Velcade and DEX for me.
Many of the previous posters in this thread have used very long cycles of proteasome inhibitor/IMID and steroid. That is generally considered the most active combination but IMO it is a very risky strategy. Here is why. A recent study showed the outcomes for patients that are relapsed and are not responding to these drugs:
"Promising new drugs are being evaluated for treatment of multiple myeloma (multiple myeloma), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed multiple myeloma, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years, and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0–8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including partial response in 69 (32%). The median overall survival and event-free survival from T0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs."
http://www.nature.com/leu/journal/v26/n1/full/leu2011196a.html
A whole 9 months of overall survival once you become refractory to these classes of drugs. Long cycles of them can get you resistant to them earlier in disease course. The reality is that the Doctors that are prescribing this type of therapy have no good therapy to use once the patients stop responding to IMIDs and proteasome inhibitors. It is easy to just prescribe the 2 best classes of drugs to their patients as soon as they are diagnosed. A skilled Doctor has a strategy to keep thier patients from becoming resistant to these 2 classes of drugs in the first place.
Mark
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Mark
Re: Looking for Feedback on Recommended First Round Treatmen
Mark,
The analogy is AIDS. As that disease ravaged those with early diagnosed HIV, various drugs were developed to stop its progression. Single agents were prescribed that worked for a while but the disease mutated and became resistant. It was only after a cocktail approach was used that AIDS became contained. Today HIV is attacked with the cocktail approach and the progression to AIDS has been contained.
A similar result is occurring with multiple myeloma. Although the disease remains incurabe, the cocktail approach using multple agents such as VRD has pushed back relapse in some cases by years. A regime of VRD is less likely to relapse than just using Velcade or Revlimid as single agents. The initial response to a multiple faceted regime has also been deeper. There are no guarantees but novel agents used in combination have the greatest potential of achieving long term remission. So far my own experience has been over 3 1/2 years with a high quality of life.
Ron
The analogy is AIDS. As that disease ravaged those with early diagnosed HIV, various drugs were developed to stop its progression. Single agents were prescribed that worked for a while but the disease mutated and became resistant. It was only after a cocktail approach was used that AIDS became contained. Today HIV is attacked with the cocktail approach and the progression to AIDS has been contained.
A similar result is occurring with multiple myeloma. Although the disease remains incurabe, the cocktail approach using multple agents such as VRD has pushed back relapse in some cases by years. A regime of VRD is less likely to relapse than just using Velcade or Revlimid as single agents. The initial response to a multiple faceted regime has also been deeper. There are no guarantees but novel agents used in combination have the greatest potential of achieving long term remission. So far my own experience has been over 3 1/2 years with a high quality of life.
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: Looking for Feedback on Recommended First Round Treatmen
Hi Ron,
So far I have used drugs from the classes of proteasome inhibitors (Velcade), alkylators (melphalan), anthracyclines (Doxil), steroid (DEX), a monoclonal antibody (ATG at my allo which kills myeloma cells) and an antimetabolite (fludarabine at my allo). I also had the graft vs myeloma from my Donor cells, so that makes 7 different therapies i have used against the myeloma. What 7 have you used so far?
Myeloma is considered curable if a patient does an allo early in disease course and the patient sustains a molecular response. The Donor immunune system can recognize the cnacer as foreign and kill it. Also, I have not had any of my white blood cell counts out of the normal range for over 8 months. That might be because I am starting 19 months off of all chemo. You on the other hand have damaged your immune system by continuos therapy with Revlimid and Velcade and need IVIG monthly to fight infections. You have to go to the clinic for the IVIG and Velcade. I only go once every 3 months for Zometa. My QOL is far superior to yours since I have a healhty functioning immune system.
It is nice to have a Doctor that know how to do something other than write prescriptions for Velcade, Revlimid and DEX.
Mark
So far I have used drugs from the classes of proteasome inhibitors (Velcade), alkylators (melphalan), anthracyclines (Doxil), steroid (DEX), a monoclonal antibody (ATG at my allo which kills myeloma cells) and an antimetabolite (fludarabine at my allo). I also had the graft vs myeloma from my Donor cells, so that makes 7 different therapies i have used against the myeloma. What 7 have you used so far?
Myeloma is considered curable if a patient does an allo early in disease course and the patient sustains a molecular response. The Donor immunune system can recognize the cnacer as foreign and kill it. Also, I have not had any of my white blood cell counts out of the normal range for over 8 months. That might be because I am starting 19 months off of all chemo. You on the other hand have damaged your immune system by continuos therapy with Revlimid and Velcade and need IVIG monthly to fight infections. You have to go to the clinic for the IVIG and Velcade. I only go once every 3 months for Zometa. My QOL is far superior to yours since I have a healhty functioning immune system.
It is nice to have a Doctor that know how to do something other than write prescriptions for Velcade, Revlimid and DEX.
Mark
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Mark
Re: Looking for Feedback on Recommended First Round Treatmen
Hi Mark, a high percentage of patients in my clinical trial at the NIH utilizing CRD have sustained sCR's at the molecular level as judged by the most advanced MRD methods in the world. Dr. Korde presented these results last week at ASH. It didn't get a lot of press like the Michigan trial. I don't know why. Those of us in the trial know how fantastic the results have been. We have 8 cycles of CRD, followed by one year of low dose Revlimid. Only time will tell how long the molecular responses will last.
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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: Looking for Feedback on Recommended First Round Treatmen
Susierose, I must inform you that your peripheral neuropathy knowledge is somewhat limited. I was given Velcade as induction therapy intraveniously and developed Grade 4 neuropathy. It required multiple ER visits for 8 weeks and the pain and cramping were so bad, I thought I would die. NOTHING would stop the pain and cramping from my waist down. After 8 weeks the pain and cramping eased and now I have to take hydromorphone just to get through the day and I will need to take it the rest of my life because of the permanent nerve damage. So don't think that you can take something to stop PN, because depending on the severity, nothing will work.
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GeorgeLJurak - Name: George Jurak
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Jan. 2011
- Age at diagnosis: 59
Re: Looking for Feedback on Recommended First Round Treatmen
Mark,
I was in no way disparaging anyone’s experience. From what you wrote it sounds like you went through the ringer but have found a treatment that has worked for you. I am happy for you and glad that you do not have to have take chemo. I hope that you can remain in that state indefinitely.
I am on IVIG as you point out, primarily because I have low Immunoglobulin’s and have had from day one before the treatments started. I contracted viral meningitis this past summer. I am an avid cyclist and live in north Texas which had an epidemic of West Nile Virus this past year. I do not know if I was bitten by an infected mosquito or not. The physicians said it was not really relevant since the treatment would be the same. I fully recovered and was able to race in a 24 hour biking endurance time trial at the end of September as part of a 3 man team. We came in first place. I also went to Belgium this past October with a group of my biking buddies and rode bikes there and walked over 70 miles during our 10 day trip. Point is I don’t feel limited in anyway on what I can or cannot do. That is how I judge my QOL. The treatments are an inconvenience not a limitation.
For example this past Thursday I received IVIG, Velcade and my oral Dex. I got back into the office by 1:30 and put in 4 hours. Then I went to Choir practice from 7 to 9. I put in a full day at the office on Friday and attended a wedding that evening getting back at 10:00. Yesterday I got up at 7:00 and was on my bike doing 50 miles. After that my wife and I went shopping at the mall for 3 ½ hours. When we got back we grabbed a quick bite and were off to an evening Christmas party and got home at midnight. This AM I was singing in the choir and just got back home. I plan on getting in “short” 25 mile ride this afternoon and finish up Christmas shopping. I also am having my sons for diner later and I do the cooking on Sundays. Does this sound like I am limited?
My oncologist attends ASH every year and stays up to date on the latest research. He is not, as you seem to imply a mere pill pusher.
Don’t get me wrong, I am only sharing my experiences. That is all any of us can do. Every person has had different reactions to the treatment. If I suffered with PN, or VRD didn’t work I am sure the approach would have been different.
I was in no way disparaging anyone’s experience. From what you wrote it sounds like you went through the ringer but have found a treatment that has worked for you. I am happy for you and glad that you do not have to have take chemo. I hope that you can remain in that state indefinitely.
I am on IVIG as you point out, primarily because I have low Immunoglobulin’s and have had from day one before the treatments started. I contracted viral meningitis this past summer. I am an avid cyclist and live in north Texas which had an epidemic of West Nile Virus this past year. I do not know if I was bitten by an infected mosquito or not. The physicians said it was not really relevant since the treatment would be the same. I fully recovered and was able to race in a 24 hour biking endurance time trial at the end of September as part of a 3 man team. We came in first place. I also went to Belgium this past October with a group of my biking buddies and rode bikes there and walked over 70 miles during our 10 day trip. Point is I don’t feel limited in anyway on what I can or cannot do. That is how I judge my QOL. The treatments are an inconvenience not a limitation.
For example this past Thursday I received IVIG, Velcade and my oral Dex. I got back into the office by 1:30 and put in 4 hours. Then I went to Choir practice from 7 to 9. I put in a full day at the office on Friday and attended a wedding that evening getting back at 10:00. Yesterday I got up at 7:00 and was on my bike doing 50 miles. After that my wife and I went shopping at the mall for 3 ½ hours. When we got back we grabbed a quick bite and were off to an evening Christmas party and got home at midnight. This AM I was singing in the choir and just got back home. I plan on getting in “short” 25 mile ride this afternoon and finish up Christmas shopping. I also am having my sons for diner later and I do the cooking on Sundays. Does this sound like I am limited?
My oncologist attends ASH every year and stays up to date on the latest research. He is not, as you seem to imply a mere pill pusher.
Don’t get me wrong, I am only sharing my experiences. That is all any of us can do. Every person has had different reactions to the treatment. If I suffered with PN, or VRD didn’t work I am sure the approach would have been different.
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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