One of the challenges I am having with doing maintenance therapy is that the use of maintenance drugs like Revlimid, or Velcade, is that the drugs *might* be selecting for resistance. In other words, while usage of the drug my initially be beneficial, in the longer term, maintenance therapy may actually select for drug resistant myeloma cells.
Are my concerns warranted? Or am I thinking too much into this?
Forums
Re: Maintenance therapy - will it select for resistance?
InQ,
This is a really good question and one which I've wondered about as well. It's an especially difficult situation since the drugs available to us don't really knock down the multiple myeloma precursors (stem cells) and their ability to generate new subclonal populations of multiple myeloma cells (which some researchers believe is the reason we tend to relapse or become refractory).
Basically, you've got this factory that is able to continue putting out a variety of new multiple myeloma cells over time, regardless of what drugs you throw into your bloodstream. And now you've got a potential situation where you may be setting up an environment for some particular subclonal lines that are coming out of this factory to thrive since you've knocked out their competition with a specific maintenance drug therapy over a prolonged period of time.
It seems like it is really a balancing act. If there is a good chance for longer PFS and OS by doing maintenance therapy to knock out those subclonal cell lines that respond to Velcade or Rev, then that "may" be a good thing (putting aside the known downsides to taking maintenance drugs like Revlimid).
But at the end of the day, you might indeed be setting yourself up for having to counter a new subclonal population of cells with a different drug...and ultimately you could have a subclonal line(s) that could be resistant to several different drugs. So, do you avoid maintenance therapy to avoid this potential outcome? Again, it seems like a balancing act to me (a non-expert layman) and a reason why you may not want to do maintenance for a very prolonged period of time.
The simple answer would seem to be that we need drugs that are much more targeted to going after the multiple myeloma cells, and to be able to do this regardless of being one variant or another.
The article below doesn't completely answer your question, but it is a long and technical read on multiple myeloma drug resistance:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926819/
Here is a simpler presentation delivered by Dr. Giralt at Sloan Kettering that acknowledges the drug resistance and clonal selection risk of maintenance therapy:
http://www.slideshare.net/spa718/maintenance-therapy-sg
I'd love to hear more on this topic from anyone with more knowledge about it.
This is a really good question and one which I've wondered about as well. It's an especially difficult situation since the drugs available to us don't really knock down the multiple myeloma precursors (stem cells) and their ability to generate new subclonal populations of multiple myeloma cells (which some researchers believe is the reason we tend to relapse or become refractory).
Basically, you've got this factory that is able to continue putting out a variety of new multiple myeloma cells over time, regardless of what drugs you throw into your bloodstream. And now you've got a potential situation where you may be setting up an environment for some particular subclonal lines that are coming out of this factory to thrive since you've knocked out their competition with a specific maintenance drug therapy over a prolonged period of time.
It seems like it is really a balancing act. If there is a good chance for longer PFS and OS by doing maintenance therapy to knock out those subclonal cell lines that respond to Velcade or Rev, then that "may" be a good thing (putting aside the known downsides to taking maintenance drugs like Revlimid).
But at the end of the day, you might indeed be setting yourself up for having to counter a new subclonal population of cells with a different drug...and ultimately you could have a subclonal line(s) that could be resistant to several different drugs. So, do you avoid maintenance therapy to avoid this potential outcome? Again, it seems like a balancing act to me (a non-expert layman) and a reason why you may not want to do maintenance for a very prolonged period of time.
The simple answer would seem to be that we need drugs that are much more targeted to going after the multiple myeloma cells, and to be able to do this regardless of being one variant or another.
The article below doesn't completely answer your question, but it is a long and technical read on multiple myeloma drug resistance:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926819/
Here is a simpler presentation delivered by Dr. Giralt at Sloan Kettering that acknowledges the drug resistance and clonal selection risk of maintenance therapy:
http://www.slideshare.net/spa718/maintenance-therapy-sg
I'd love to hear more on this topic from anyone with more knowledge about it.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Maintenance therapy - will it select for resistance?
I see your point. My own experience was no maintenance drugs. I was in remission before my stem cell transplant and after for 3 years. I started Revlimid last month after my M-1 starting showing presence and my light chains started showing again. After one 21 day regimen my numbers have dropped.
In my case, I was seeing the doctor every 3 months with a full set of blood and urine work. I can't say that anything would have changed had I been on maintenance, and, in fact, I might have suffered the very thing that concerns you.
So for me, in remission, I think no maintenance was a good thing.
In my case, I was seeing the doctor every 3 months with a full set of blood and urine work. I can't say that anything would have changed had I been on maintenance, and, in fact, I might have suffered the very thing that concerns you.
So for me, in remission, I think no maintenance was a good thing.
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Wayne K - Name: Wayne
- Who do you know with myeloma?: Myself, my sister who passed in '95
- When were you/they diagnosed?: 03/09
- Age at diagnosis: 70
Re: Maintenance therapy - will it select for resistance?
InQ and Multibilly,
The maintainance question with Revlimid pertains to exactly where I am in this continuous battle.
I have achieved VGPR (0.1 M-spike), no transplant, and a year and a half on Revlimid maintainenance.
My oncologist wants me to stay on Revlimid until disease progression; I would like to stop taking Revlimid.
Tough decision.
Thanks,
Coach Hoke
The maintainance question with Revlimid pertains to exactly where I am in this continuous battle.
I have achieved VGPR (0.1 M-spike), no transplant, and a year and a half on Revlimid maintainenance.
My oncologist wants me to stay on Revlimid until disease progression; I would like to stop taking Revlimid.
Tough decision.
Thanks,
Coach Hoke
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: Maintenance therapy - will it select for resistance?
Coachhoke,
Tough decision. Have you gotten a second opinion on the matter?
I'm also always scared of secondary cancers from Rev, as is my main "go-to" oncologist. I just found a lump in my breast a few days ago...I checked for these since my sister just recently died of ovarian cancer after they found she had a BRCA-2 gene...doc thinks it's just a typical, benign lump that males get, but I'm going to get it biopsied just to be safe). So, I now tend to really pay attention to these secondary cancer graphs that you see with Rev studies.
I can't really put myself in your shoes, but I would definitely be carefully weighing all the tradeoffs and getting 2-3 professional opinions on the matter. Again, no simple answer and I feel for you having to make this choice.
Tough decision. Have you gotten a second opinion on the matter?
I'm also always scared of secondary cancers from Rev, as is my main "go-to" oncologist. I just found a lump in my breast a few days ago...I checked for these since my sister just recently died of ovarian cancer after they found she had a BRCA-2 gene...doc thinks it's just a typical, benign lump that males get, but I'm going to get it biopsied just to be safe). So, I now tend to really pay attention to these secondary cancer graphs that you see with Rev studies.
I can't really put myself in your shoes, but I would definitely be carefully weighing all the tradeoffs and getting 2-3 professional opinions on the matter. Again, no simple answer and I feel for you having to make this choice.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Maintenance therapy - will it select for resistance?
Thanks Multibilly,
No I have not gotten a second opinion. I think it is just a flip of the coin. I'm not as concerned with secondary cancers as I am with quality of life (NO major side effects, one blood clot and thus now taking warafin) and, as you and InQ suggested, maybe I'm using up a good bullet and promoting resistance when I do progress.
thanks again,
Coach Hoke
No I have not gotten a second opinion. I think it is just a flip of the coin. I'm not as concerned with secondary cancers as I am with quality of life (NO major side effects, one blood clot and thus now taking warafin) and, as you and InQ suggested, maybe I'm using up a good bullet and promoting resistance when I do progress.
thanks again,
Coach Hoke
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: Maintenance therapy - will it select for resistance?
I will soon be faced with the decision as to whether I go on maintenance therapy or not. I was diagnosed in June 2013, had 5 cycles of Velcade-Revlimid-dex (VRD) and had a complete remission. I had an auto stem cell transplant (SCT) in Feb 2014 and am still in CR.
My transplant doctor who is a myeloma specialist is suggesting that I do NOT have any maintenance therapy now but take a wait and see approach and get tested monthly. I will soon start seeing the oncologist I originally started out with and, based on what he's told me in the past, I'm guessing he'll want me to go on Revlimid maintenance.
My oncologist and transplant doctor know each other and can discuss my case, so I hope they come to some sort of agreement on what to do next. As the patient with a goal of surviving the longest I can with this disease, it's confusing as to what to do next. If I knew that the overall survival is the same or better if I forego the maintenance therapy now, I'd skip the maintenance therapy now and just wait until I relapse in order to start it.
Are there any studies that show that overall survival is better or worse based on whether you go on maintenance therapy or not?
My transplant doctor who is a myeloma specialist is suggesting that I do NOT have any maintenance therapy now but take a wait and see approach and get tested monthly. I will soon start seeing the oncologist I originally started out with and, based on what he's told me in the past, I'm guessing he'll want me to go on Revlimid maintenance.
My oncologist and transplant doctor know each other and can discuss my case, so I hope they come to some sort of agreement on what to do next. As the patient with a goal of surviving the longest I can with this disease, it's confusing as to what to do next. If I knew that the overall survival is the same or better if I forego the maintenance therapy now, I'd skip the maintenance therapy now and just wait until I relapse in order to start it.
Are there any studies that show that overall survival is better or worse based on whether you go on maintenance therapy or not?
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DallasGG - Name: Kent
- Who do you know with myeloma?: myself
- When were you/they diagnosed?: 6/20/2013
- Age at diagnosis: 56
Re: Maintenance therapy - will it select for resistance?
Hi Kent,
Maintenance therapy is an unsettled issue right now in multiple myeloma precisely because there is conflicting evidence as to whether or not it is beneficial.
The Beacon's tag (topic) page for maintenance therapy is probably a good place to start if you really want to dig deep into the subject:
https://myelomabeacon.org/tag/maintenance-therapy/
Also, this preview for the recent American Society of Hematology meeting gives a flavor for some of the issues related to maintenance therapy, although there are maintenance regimens discussed in the article that probably are not relevant to your case:
ASH 2013 Preview: Revlimid Maintenance Therapy For Multiple Myeloma
The major studies about Revlimid maintenance were first published in 2012, and the Beacon published a detailed article about it that gives some good background about the controversy. It may actually be a good place to start before you dig into some of the links above:
Revlimid Maintenance Therapy: Three Major Studies Clarify The Benefits And Risks
The short answer to your question is that there have been three major studies that have investigated Revlimid maintenance therapy. One of them has shown an overall survival benefit to maintenance therapy, while the other two have not.
Maintenance therapy is an unsettled issue right now in multiple myeloma precisely because there is conflicting evidence as to whether or not it is beneficial.
The Beacon's tag (topic) page for maintenance therapy is probably a good place to start if you really want to dig deep into the subject:
https://myelomabeacon.org/tag/maintenance-therapy/
Also, this preview for the recent American Society of Hematology meeting gives a flavor for some of the issues related to maintenance therapy, although there are maintenance regimens discussed in the article that probably are not relevant to your case:
ASH 2013 Preview: Revlimid Maintenance Therapy For Multiple Myeloma
The major studies about Revlimid maintenance were first published in 2012, and the Beacon published a detailed article about it that gives some good background about the controversy. It may actually be a good place to start before you dig into some of the links above:
Revlimid Maintenance Therapy: Three Major Studies Clarify The Benefits And Risks
The short answer to your question is that there have been three major studies that have investigated Revlimid maintenance therapy. One of them has shown an overall survival benefit to maintenance therapy, while the other two have not.
Re: Maintenance therapy - will it select for resistance?
It seems to me that all three of these major studies dealt with transplants and then maintainance. Are there any with no transplants (just consolidation) followed by maintenance? And, secondly, did they all have CR, or were some VGPR?
Thanks,
Coach Hoke
Thanks,
Coach Hoke
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: Maintenance therapy - will it select for resistance?
Coach Hoke,
The CALGB and IFM trials did involve maintenance therapy after transplantation. The MM-015 trial, however, included only patients who did not undergo a stem cell transplant.
Patients in the studies were randomly assigned to receive Revlimid or placebo, regardless of their response to the initial treatment they included.
Again, just to be clear, when it came time to decide whether a patient in these trials received Revlimid or a placebo as maintenance therapy, the decision was based on a coin flip (or the computer equivalent). The patient's response to initial treatment did not play a role in the decision.
It's possible that there may be analyses of the data looking at whether maintenance therapy was more beneficial, for example, in patients in the trials who did not achieve a complete response (CR) to initial therapy. That would be an interesting analysis to see, but we're not sure whether it's been done.
The CALGB and IFM trials did involve maintenance therapy after transplantation. The MM-015 trial, however, included only patients who did not undergo a stem cell transplant.
Patients in the studies were randomly assigned to receive Revlimid or placebo, regardless of their response to the initial treatment they included.
Again, just to be clear, when it came time to decide whether a patient in these trials received Revlimid or a placebo as maintenance therapy, the decision was based on a coin flip (or the computer equivalent). The patient's response to initial treatment did not play a role in the decision.
It's possible that there may be analyses of the data looking at whether maintenance therapy was more beneficial, for example, in patients in the trials who did not achieve a complete response (CR) to initial therapy. That would be an interesting analysis to see, but we're not sure whether it's been done.
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