First, I want to emphasize that I am not a doctor, and only became myeloma literate through my own research. I am an engineer by profession. I do not suggest that anyone adapt any of my ideas without consulting with their oncologists first. This worked for me, but may not work for others.
I was diagnosed with stage 3 multiple myeloma back in April 2009 when I was 54. Went through Velcade, Revlimid, dexamethasone (VRD) chemo for 7 months and got complete remission for 2 years. Interestingly enough, I had just completed the procedure for the collection of my own stem cells, that I was planning to put on hold if I ever needed them later on and the insurance had paid for it. Could the stem cell stimulation drugs cause my myeloma to come out of remission ? My doctor said no.
My doctor was pushing me to do the stem cell transplant, but I was not interested as long as I was having a good response from the Revlimid maintenance and my plan was to undergo monthly multiple myeloma labwork, monitor the results, assess what worked and didn't work, and make quick notes of my lifestyle,supplements,diet,etc. for each month. He agreed to let me try.
Fortunately my condition is the light protein chain (kappa) variety without the aggressive chromosome deletion form. For me, I pay particular attention to the level of the kappa light chain. My ideal level appears to be around 20-25 mg/l while 19 is the upper reference range.
While the maintenance plan called for monthly use of Revlimid / dex, I tried taking the treatment at different intervals – skip a month, or 2 months on and 2 months off. The monthly myeloma labs allowed me to get quick feedback on how to reduce dosage frequency and still manage the disease. These myeloma labs were cheap and even when the insurance didn't pay for them, they were less than $100.
This worked well until late 2014 where I was getting the expected resistance and my kappa levels approached 50 and M-spike= 0.3 g/dL. But maybe not since I was leaving out the dex (in hindsight, I should have stayed on the low dosage dex as this amplifies the effectiveness of the drug).
My doctor decided to have me try Pomalyst / dex in October 2014 after 2 straight months of ineffective Revlimid / dex results before. I was now seeing a very effective outcome – the kappa dropped down to 34 and M-spike went to zero. A second month of Pomalyst / dex I saw my kappa drop to 23. A third month only saw the kappa go to 21.
Afterwards, I stopped maintenance, followed a high anti- inflammatory diet, curcumin, tart cherry juice, sweet potatoes, flax, chia, hempseed, high in cruciferous vegetables with less meat, dairy, packaged foods, other carbs And a good walking routine 45-60 minutes 5 days a week.
Regular monthly monitoring of my myeloma labs over 10 months showed a flat line until month 9, where it reached high 30s, then 46 in month 10 with a 0.3 M-spike. In month 11, I then continued the Pomalyst and noticed a similarly effective drop to 33 and zero M-spike that I had seen 10 months ago.
I found it interesting that almost a year later after starting the Pomalyst / dex , I had gotten a similar spectacular response in reducing the kappa level as I did a year earlier after Month 1.
Is this approach a good way to deal with resistance instead of taking this maintenance regimen every month as prescribed?
That is my question. I know that resistance occurs when the DNA in the cancer cell adapts to the new stresses placed upon it by regular use of the drug. However, a very infrequent use of the drug might not give the cancer DNA time to adapt – maybe??
I am currently in Month 2 of taking the Pomalyst / dex and am curious to see if the kappa drops to <25 as a repeat of 10 months ago. If my next monthly myeloma lab shows a low kappa (<25) and no M-spike, Should this happen, I would then repeat taking no more maintenance until my monthly kappa level approaches 50 mg/l. With no guarantees, I will see what happens on my next myeloma lab results.
My thoughts are this maintenance therapy is very expensive and perhaps taking the drugs monthly is excessive for some people with less aggressive myeloma and those myelomas that have definite markers present in myeloma lab tests that can be tracked.. '
For those patients, the benefit of keeping a monthly log of myeloma labs will provide data to any patient wanting to know what the month's therapy did to their cancer.
I know this sounds like customizing treatment for individual patients, which is taboo – something that many oncologists find threatening since they are bent on strictly following the exact procedures based in research studies on hundreds of patients. I am blessed with an oncologist who is giving me free reign to try these approaches that works for me based on real data that affects my reaction to the drug and my desire to reduce high exposure to a drug that would eventually cause resistance to occur.
Just my thought that I wanted to share with others.
Edit Nov 10, 2015: Corrected kappa free light chain units.
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Combating Revlimid or Pomalyst resistance
Last edited by smithwcs on Tue Nov 10, 2015 7:36 am, edited 1 time in total.
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smithwcs - Name: Will
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: Apr 2009
- Age at diagnosis: 54
Re: Combating Revlimid or Pomalyst resistance
Will
I have wondered like you whether after obtaining CR or very low level of light chains/ M protein whether ongoing drug treatment can confer resistance. Some plasma clones become more aggressive when others are knocked out in treatment, so it is difficult to know. I expect aggressive disease may lead to resistance faster, being able to 'change'. its response to drugs faster.
Not many studies look at these factors, the drug companies seem to publish results suggesting benefits of continuing treatment, so now maintenance has become ingrained in how doctors treat.
I was interested to read that some years ago it was known that in renal insufficiency, lenalidomide excreted by the kidney, showed greater toxicity. Clinical trials exclude patients below a specified creatinine clearance level, so this information might not come out from clinical trials. The build up of toxic drugs in the body could easily occur over time in the many myeloma patients whose kidneys do not function optimally. The affect of having these drugs 'accumulating' may not be just myelosupression but also increasing drug resistance, as apparently dose reductions of lenalidomide were not made early in the course of treatment.
I feel treatment decisions are not based on enough relevant research but too much focus on clinical trials selective of participants.
So like you I would like more and wider research into the factors which might help to mitigate resistance to a drug in different patient scenarios. I suspect it will not be clear cut as myeloma is so variable in its presentation and evolution. There are patients in the UK who have had CR at induction without stem cell transplant and been drug free for 5 years. What is it that helped?
We need to be clear for whom maintenance actually has benefit and the risks for individuals with their particular situations.
Edna
I have wondered like you whether after obtaining CR or very low level of light chains/ M protein whether ongoing drug treatment can confer resistance. Some plasma clones become more aggressive when others are knocked out in treatment, so it is difficult to know. I expect aggressive disease may lead to resistance faster, being able to 'change'. its response to drugs faster.
Not many studies look at these factors, the drug companies seem to publish results suggesting benefits of continuing treatment, so now maintenance has become ingrained in how doctors treat.
I was interested to read that some years ago it was known that in renal insufficiency, lenalidomide excreted by the kidney, showed greater toxicity. Clinical trials exclude patients below a specified creatinine clearance level, so this information might not come out from clinical trials. The build up of toxic drugs in the body could easily occur over time in the many myeloma patients whose kidneys do not function optimally. The affect of having these drugs 'accumulating' may not be just myelosupression but also increasing drug resistance, as apparently dose reductions of lenalidomide were not made early in the course of treatment.
I feel treatment decisions are not based on enough relevant research but too much focus on clinical trials selective of participants.
So like you I would like more and wider research into the factors which might help to mitigate resistance to a drug in different patient scenarios. I suspect it will not be clear cut as myeloma is so variable in its presentation and evolution. There are patients in the UK who have had CR at induction without stem cell transplant and been drug free for 5 years. What is it that helped?
We need to be clear for whom maintenance actually has benefit and the risks for individuals with their particular situations.
Edna
Re: Combating Revlimid or Pomalyst resistance
Edna and Will,
I am on the same page as you two. I understand that some forms of myeloma need to be treated more aggressively than others. I also understand that each patient responds differently to the same treatments.
My oncologist swears that you do not get resistant to Revlimid (but whatever you want to call it, ultimately you relapse while still taking the Revlimid). I have experimented and charted my M-spike for two years and found that 2.5 mg of Revlimid got my M-spike to its lowest point 0.1g/dl. (I never had a transplant; my medications went from Velcade and dex, to just Velcade, to just 15 mg of Revlimid (no dex), to 10 mg of just Revlimid, to 5 mg to 2.5 mg to a drug holiday the last 10 months.) My M-spike went from 0.9 to 0.12 from the start of treatment until I stopped taking any medication.
I plan to re-start with 2.5 mg of Revlimid when my disease progresses (and that's a whole other story as to determining relapse).
Coach Hoke
I am on the same page as you two. I understand that some forms of myeloma need to be treated more aggressively than others. I also understand that each patient responds differently to the same treatments.
My oncologist swears that you do not get resistant to Revlimid (but whatever you want to call it, ultimately you relapse while still taking the Revlimid). I have experimented and charted my M-spike for two years and found that 2.5 mg of Revlimid got my M-spike to its lowest point 0.1g/dl. (I never had a transplant; my medications went from Velcade and dex, to just Velcade, to just 15 mg of Revlimid (no dex), to 10 mg of just Revlimid, to 5 mg to 2.5 mg to a drug holiday the last 10 months.) My M-spike went from 0.9 to 0.12 from the start of treatment until I stopped taking any medication.
I plan to re-start with 2.5 mg of Revlimid when my disease progresses (and that's a whole other story as to determining relapse).
Coach Hoke
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: Combating Revlimid or Pomalyst resistance
Hi Will,
Thanks a lot for detailing your treatment approach and results for us. You've raised a very interesting question - does continuous maintenance therapy make it more likely that the patient will develop resistance to that therapy, through the evolution of a myeloma clone that is resistant? And a corollary question - if so (or if we don't know the answer, but we're concerned about the possibility), is there a way get the benefits of maintenance therapy while minimizing the possibility of the resistant clone?
Great questions! I think your "on-again-off-again" maintenance treatment approach sounds pretty logical, as you've explained it.
As you may know, there was a guest column in the Beacon last year by Dr. Gareth Morgan of the University of Arkansas discussing the importance of clonal evolution and intra-clonal heterogeneity in multiple myeloma. (https://myelomabeacon.org/news/2014/11/03/evolution-intra-clonal-heterogeneity-multiple-myeloma/)
I'm trying a different, more conventional approach than you - continuous Revlimid maintenance for as long as I can handle it or until relapse. I don't know whether this approach is any better or worse than your approach. But it does give me a little psychological comfort to feel like I'm doing all that I can to keep knocking the myeloma down. And I realize that other folks may feel more secure (although we never feel very secure with multiple myeloma, do we?) doing no maintenance or a hybrid approach like yours.
I have one little quibble with your post, though. You mentioned that personalized treatment is "taboo." I think things are moving in the opposite direction, where there is a growing awareness of the importance of personalized treatment and lots of effort to determine what predictive factors should be used to personalize treatment. As an example, there are several Beacon news articles tagged with "personalized therapy." (https://myelomabeacon.org/tag/personalized-therapy/)
Best of luck to you. I hope your treatment approach keeps working well for you for a long, long time!
Mike
Thanks a lot for detailing your treatment approach and results for us. You've raised a very interesting question - does continuous maintenance therapy make it more likely that the patient will develop resistance to that therapy, through the evolution of a myeloma clone that is resistant? And a corollary question - if so (or if we don't know the answer, but we're concerned about the possibility), is there a way get the benefits of maintenance therapy while minimizing the possibility of the resistant clone?
Great questions! I think your "on-again-off-again" maintenance treatment approach sounds pretty logical, as you've explained it.
As you may know, there was a guest column in the Beacon last year by Dr. Gareth Morgan of the University of Arkansas discussing the importance of clonal evolution and intra-clonal heterogeneity in multiple myeloma. (https://myelomabeacon.org/news/2014/11/03/evolution-intra-clonal-heterogeneity-multiple-myeloma/)
I'm trying a different, more conventional approach than you - continuous Revlimid maintenance for as long as I can handle it or until relapse. I don't know whether this approach is any better or worse than your approach. But it does give me a little psychological comfort to feel like I'm doing all that I can to keep knocking the myeloma down. And I realize that other folks may feel more secure (although we never feel very secure with multiple myeloma, do we?) doing no maintenance or a hybrid approach like yours.
I have one little quibble with your post, though. You mentioned that personalized treatment is "taboo." I think things are moving in the opposite direction, where there is a growing awareness of the importance of personalized treatment and lots of effort to determine what predictive factors should be used to personalize treatment. As an example, there are several Beacon news articles tagged with "personalized therapy." (https://myelomabeacon.org/tag/personalized-therapy/)
Best of luck to you. I hope your treatment approach keeps working well for you for a long, long time!
Mike
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Combating Revlimid or Pomalyst resistance
Smithwcs,
Just to add my experience of late, I was on 25 mg Revlimid and 20 mg dexamethasone for maintenance, which is essentially the full dose. My maintenance dose had been steadily increasing over a year as lab work showed it was becoming increasing ineffective. But then when Revlimid stopped working for me, it stopped pretty suddenly. I had developed a new light chain kappa clone of myeloma and my kappa light chain levels soared to 3000 mg/L.
I switched to Velcade and 40 mg of dexamethasone, which was used in my induction therapy with great success four years ago. This time with Velcade, I maintained my kappa light chains to between 2500 mg/L and 3000 mg/L for about 3 months. Not good results.
I switched to Pomalyst 3 mg with 40 mg dexamethasone and within 1 month my kappa light chains dropped to 100 mg/L from 3000 mg/L. Really good results. Unfortunately, Pomalyst really affected my blood counts. At the end of the first 3-week cycle, just before my off week, my hemoglobin was down to 9 g/dl, platelets to as low as 50,000 / mcL and white neutrophils down below the normal range even with 40 mg of dexamethasone. I ended up getting pneumonia and a 3-day hospital stay. I recovered from that, been off the chemo for about three weeks, but started up again last Sunday. I will see how the next month goes.
Also, are the units on your kappa light chains right? My lab results for kappa light chains are reported in mg/L with a normal range of 3-19 mg/L. You reported yours in g/dl with a normal high of 19 g/dl. That would be 190,000 mg/L. I have other lab results that are in g/dl.
Just to add my experience of late, I was on 25 mg Revlimid and 20 mg dexamethasone for maintenance, which is essentially the full dose. My maintenance dose had been steadily increasing over a year as lab work showed it was becoming increasing ineffective. But then when Revlimid stopped working for me, it stopped pretty suddenly. I had developed a new light chain kappa clone of myeloma and my kappa light chain levels soared to 3000 mg/L.
I switched to Velcade and 40 mg of dexamethasone, which was used in my induction therapy with great success four years ago. This time with Velcade, I maintained my kappa light chains to between 2500 mg/L and 3000 mg/L for about 3 months. Not good results.
I switched to Pomalyst 3 mg with 40 mg dexamethasone and within 1 month my kappa light chains dropped to 100 mg/L from 3000 mg/L. Really good results. Unfortunately, Pomalyst really affected my blood counts. At the end of the first 3-week cycle, just before my off week, my hemoglobin was down to 9 g/dl, platelets to as low as 50,000 / mcL and white neutrophils down below the normal range even with 40 mg of dexamethasone. I ended up getting pneumonia and a 3-day hospital stay. I recovered from that, been off the chemo for about three weeks, but started up again last Sunday. I will see how the next month goes.
Also, are the units on your kappa light chains right? My lab results for kappa light chains are reported in mg/L with a normal range of 3-19 mg/L. You reported yours in g/dl with a normal high of 19 g/dl. That would be 190,000 mg/L. I have other lab results that are in g/dl.
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
Re: Combating Revlimid or Pomalyst resistance
Will,
Like you, I'm a kappa guy using my light chains to measure effectiveness of treatment. I passed on the doctor's suggestion of maintenance for life. I strongly believe you are less likely to develop resistance if you don't have the drugs constantly in your system.
I stopped all Revlimid in April and I'm just now starting to see some slight increase in light chains. My sweet spot is 10 - 15 d/l. My plan is to do 10 mg of Revlimid daily during winter with the summer off. How well that plan works long term is unknown.
Glad to see you have been doing something similar.
Jerry
Like you, I'm a kappa guy using my light chains to measure effectiveness of treatment. I passed on the doctor's suggestion of maintenance for life. I strongly believe you are less likely to develop resistance if you don't have the drugs constantly in your system.
I stopped all Revlimid in April and I'm just now starting to see some slight increase in light chains. My sweet spot is 10 - 15 d/l. My plan is to do 10 mg of Revlimid daily during winter with the summer off. How well that plan works long term is unknown.
Glad to see you have been doing something similar.
Jerry
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JBarnes - Name: Jerry Barnes
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: Aug 17, 2012
- Age at diagnosis: 54
Re: Combating Revlimid or Pomalyst resistance
I want to thank you all for your input on this very important topic. Eric, I corrected the units on the kappa to mg/l. Sorry for that confusion.
Coach Hoke and JBarnes - Glad to see that you guy are taking those intermittent holidays too and getting success. I had only been taking 10 mg Revlimid prior to my recent change over to 4 mg Pomalyst.
Edna - You bring up an important point about toxicity build up in the kidneys, and may I say liver, from continual or high dosage Revlimid and certainly dex. Obviously, when the multiple myeloma is getting aggressive, the aim of treatment is to control the cancer as quickly as possible, and that explains the high dosage toxicity. Again, for myself, that is why I am closely tracking my blood labs carefully with every change in dosage to find the sweet spot where I get the immediate improvement in my kappa levels, and then if I can, try to ease off dosage when the improvement in kappa levels have plateaued. That way, any toxic build up would lessen. I also practice the liver cleansing routine that Dr. Gonzales advocates. I think it is a good way to rid the body of not just the toxic drug build up, but also the dead cancer cells. Again, I'm not a doctor, but I would imagine this would help with blood chemistry, together with a very targeted healthy diet and elevating ones respiratory system through some aerobic activity.
Mikeb - I was very interested in your link to Dr. Gareth Morgan's article on intraclonal heterogeneity (ICH) in regards to multiple myeloma. Thanks greatly ! He mentions how a particular dominant multiple myeloma subclone is aggressively reduced by a particular drug, but that there is opportunity for other lesser subclones with greater immunity to the drug to then become the new dominant subclone. Hence, sounds like relapse is at hand in this case, and he supports the use of a multiple drug cocktail to eradicate the multiple subclones. Its a great idea, and I didn't really understand before why the research was headed towards combining multiple effective drugs instead of just one. Of course, this might bring up the notion that the continual use of the multiple drugs over time could cause relapse on all of them if any subclones got missed. Terrible thought.
I am thinking that if it isn't yet possible to eliminate all of the newly emerging subclones, otherwise there would be a cure, why not encourage the return of a prior subclone which was effectively killed back by a particular drug ? So, getting back to the approach of intermittent Revlimid or Pomalyst usage. If instead, suppose we just try to reduce the dominant subclone to an acceptable level in very short two or three cycles, meaning we don't cut the grass too short, and the kappa level drops as desired. So if there weren't any marked DNA changes or opportunity for the lesser more immune subclones to return as the dominant ones, then perhaps the original Revlimid affected subclone retuns as the dominant one and the later 9-10 month Revlimid treatment effectively reduces the same subclone one again. Repeating this over time might forestall the eventual relapse by a significant amount.
Just a follow up thought on my interpretation of how one could apply Dr. Morgans concept. Let me know what you guys think.
Coach Hoke and JBarnes - Glad to see that you guy are taking those intermittent holidays too and getting success. I had only been taking 10 mg Revlimid prior to my recent change over to 4 mg Pomalyst.
Edna - You bring up an important point about toxicity build up in the kidneys, and may I say liver, from continual or high dosage Revlimid and certainly dex. Obviously, when the multiple myeloma is getting aggressive, the aim of treatment is to control the cancer as quickly as possible, and that explains the high dosage toxicity. Again, for myself, that is why I am closely tracking my blood labs carefully with every change in dosage to find the sweet spot where I get the immediate improvement in my kappa levels, and then if I can, try to ease off dosage when the improvement in kappa levels have plateaued. That way, any toxic build up would lessen. I also practice the liver cleansing routine that Dr. Gonzales advocates. I think it is a good way to rid the body of not just the toxic drug build up, but also the dead cancer cells. Again, I'm not a doctor, but I would imagine this would help with blood chemistry, together with a very targeted healthy diet and elevating ones respiratory system through some aerobic activity.
Mikeb - I was very interested in your link to Dr. Gareth Morgan's article on intraclonal heterogeneity (ICH) in regards to multiple myeloma. Thanks greatly ! He mentions how a particular dominant multiple myeloma subclone is aggressively reduced by a particular drug, but that there is opportunity for other lesser subclones with greater immunity to the drug to then become the new dominant subclone. Hence, sounds like relapse is at hand in this case, and he supports the use of a multiple drug cocktail to eradicate the multiple subclones. Its a great idea, and I didn't really understand before why the research was headed towards combining multiple effective drugs instead of just one. Of course, this might bring up the notion that the continual use of the multiple drugs over time could cause relapse on all of them if any subclones got missed. Terrible thought.
I am thinking that if it isn't yet possible to eliminate all of the newly emerging subclones, otherwise there would be a cure, why not encourage the return of a prior subclone which was effectively killed back by a particular drug ? So, getting back to the approach of intermittent Revlimid or Pomalyst usage. If instead, suppose we just try to reduce the dominant subclone to an acceptable level in very short two or three cycles, meaning we don't cut the grass too short, and the kappa level drops as desired. So if there weren't any marked DNA changes or opportunity for the lesser more immune subclones to return as the dominant ones, then perhaps the original Revlimid affected subclone retuns as the dominant one and the later 9-10 month Revlimid treatment effectively reduces the same subclone one again. Repeating this over time might forestall the eventual relapse by a significant amount.
Just a follow up thought on my interpretation of how one could apply Dr. Morgans concept. Let me know what you guys think.
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smithwcs - Name: Will
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: Apr 2009
- Age at diagnosis: 54
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