A quick follow-up ... We just took a look at the presentation with updated results from the IFM (French) Revlimid maintenance trial that was given at the 2013 American Society of Hematology meeting this past December.
As it turns out, there is an analysis in that slide deck of whether or not Revlimid maintenance or placebo was better based on whether or not the patient had a very good partial response (VGPR) or better before maintenance was started.
As it turns out, in patients who had less than a VGPR before the start of maintenance therapy, those who received the placebo as "maintenance therapy" had a slightly better overall survival than those who received Revlimid maintenance.
Note, however, that the difference in overall survival between the placebo and Revlimid patients in this group is truly slight, and statistically insignificant.
There is no difference in overall survival among the patients who had a VGPR or better, and received either Revlimid or placebo as maintenance.
It turns out that If you look at the published results for the CALGB trial, which are now available publicly here,
http://www.nejm.org/doi/full/10.1056/NEJMoa1114083#t=article
Figure 2 in the article shows sub analyses that indicate that Revlimid maintenance was better than placebo maintenance, in terms of overall survival, for patients who did not achieve a complete response (CR) prior to their maintenance therapy.
So that result is different than what was seen in the IFM trial.
The difference in the results may be because the cutoff in the CALGB analysis was CR, and for the IFM analysis it was VGPR. Or it may just be that the results are fundamentally different between the CALGB and IFM trials.
(Dr. Michel Attal was kind enough to share his ASH slides with us to help with our coverage of the meeting; however, we do not have permission at this time to make them publicly available. Sorry!)
Forums
Re: Maintenance therapy - will it select for resistance?
Thanks everyone for your thoughts on the question.
Re: Maintenance therapy - will it select for resistance?
In January 2013, after the ASCT, I was proposed maintenance with lenalidomide [Revlimid] by my hematologist. I was, and still am, in remission with a VGPR. I also invested privately, going to discuss the matter with three more specialists. Only one was against it, saying that the danger was that by the time you really needed it, the drug would lose its efficacy.
I then wrote to Susie Novis, founder of the IMF, after having the pleasure of meeting her in person in Rome at the conference she and her husband organised. Her colleague answered that while lenalidomide might lose its efficiency, we can now rely on other, newer drugs which should still work.
After reading more articles I decided that there were no clear answers, and I decided
not to take it as maintenance. From what I understand, remission is longer, but not so survival. One of the article which convinced me was from Robert A. Kyle, MD, of the Mayo Clinic. Here it is:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084644/
I also discovered this interesting 2013 article which presents opposing views on the matter:
http://journals.lww.com/oncology-times/blog/onlinefirst/pages/post.aspx?PostID=777
Hope I did not just add to the confusion! Ciao!
I then wrote to Susie Novis, founder of the IMF, after having the pleasure of meeting her in person in Rome at the conference she and her husband organised. Her colleague answered that while lenalidomide might lose its efficiency, we can now rely on other, newer drugs which should still work.
After reading more articles I decided that there were no clear answers, and I decided
not to take it as maintenance. From what I understand, remission is longer, but not so survival. One of the article which convinced me was from Robert A. Kyle, MD, of the Mayo Clinic. Here it is:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084644/
I also discovered this interesting 2013 article which presents opposing views on the matter:
http://journals.lww.com/oncology-times/blog/onlinefirst/pages/post.aspx?PostID=777
Hope I did not just add to the confusion! Ciao!
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Annamaria - Name: Annamaria
- Who do you know with myeloma?: I am a patient
- When were you/they diagnosed?: April 2012
- Age at diagnosis: 58
Re: Maintenance therapy - will it select for resistance?
These are great articles Annamaria. Just wish there would be more discussion and research on the subject wrt those that don't opt for transplants.
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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?
How about individual experience, anecdotal evidence.?
I never had a transplant and have been on maintenance for last 4 years. For the last two, it has been VD (a shot of Velcade and 8 mg of dex) once every two weeks. No progression, diagnosed over 5 years ago. Very physically active - avid cyclist and full time employment without missing work except for time in treatments.
Was original diagnosed with IgG kappa light chain multiple myeloma – Stage II. Reached a CR with VRD [Velcade-Revlimid-dexamethasone] within 6 months. Never have had a chemo holiday, never had a stem cell transplant.
I never had a transplant and have been on maintenance for last 4 years. For the last two, it has been VD (a shot of Velcade and 8 mg of dex) once every two weeks. No progression, diagnosed over 5 years ago. Very physically active - avid cyclist and full time employment without missing work except for time in treatments.
Was original diagnosed with IgG kappa light chain multiple myeloma – Stage II. Reached a CR with VRD [Velcade-Revlimid-dexamethasone] within 6 months. Never have had a chemo holiday, never had a stem cell transplant.
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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: Maintenance therapy - will it select for resistance?
Thanks everybody for responding. I appreciate your pointing out all these studies. One thing that seems clear to me is that there is no consensus. So I'll just flip a coin or go "rock, scissors, paper" with my oncologist.
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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 am glad you liked the articles, Multibilly 
It seems to me that, with our disease, tossing the coin is bound to happen. And I think that some of the factors influencing our choices are not rational.
I should have said yes to lenalidomide, but I did not want to worsen quality of my life, for instance fatigue would prevent me from swimming, which I love so much. So I convinced myself that those who speak in favour of the "wait and see" tactic are right.
I might regret it , maybe the day my remission ends I will think "Oh, I wish I listened to my doctor!" After I finally decided, though, my mind found peace, and so far I do not regret my choice.
It seems to me that, with our disease, tossing the coin is bound to happen. And I think that some of the factors influencing our choices are not rational. I should have said yes to lenalidomide, but I did not want to worsen quality of my life, for instance fatigue would prevent me from swimming, which I love so much. So I convinced myself that those who speak in favour of the "wait and see" tactic are right.
I might regret it , maybe the day my remission ends I will think "Oh, I wish I listened to my doctor!" After I finally decided, though, my mind found peace, and so far I do not regret my choice.
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Annamaria - Name: Annamaria
- Who do you know with myeloma?: I am a patient
- When were you/they diagnosed?: April 2012
- Age at diagnosis: 58
Re: Maintenance therapy - will it select for resistance?
I wonder why there is not research on rotation of maintenance therapies. For example, the patient takes Revlimid for 3 months, Velcade for the next 3 month, nothing for 3 months (let the immune system do some of the killing), then some other therapy for 3 month, etc, etc.
It seems with each different therapy, you'd be clearing out the myeloma cells that were resistant to the prior therapy.
It's what us farmers do to avoid resistance when using fungicides. If we use the same fungicide, resistant fungus populations builds up very quickly. If we rotate chemistry, resistance does not appear to happen at all.
Even the chemical companies work together and will recommend using a competitor's product before using their own product again during that same season.
It seems with each different therapy, you'd be clearing out the myeloma cells that were resistant to the prior therapy.
It's what us farmers do to avoid resistance when using fungicides. If we use the same fungicide, resistant fungus populations builds up very quickly. If we rotate chemistry, resistance does not appear to happen at all.
Even the chemical companies work together and will recommend using a competitor's product before using their own product again during that same season.
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Stann
Re: Maintenance therapy - will it select for resistance?
Fascinating idea Stann ... all the farmers out there are probably saying "duh, of course this makes sense ... my great Grandad understood this concept"
Or you wonder if doing this would instead create an equal playing ground for multiple clonal lines to all thrive in relatively equal numbers (which might not necessarily be a bad thing??). I'm thinking this might be the case with multiple myeloma, since you have the stem cells in place and at the ready to produce more multiple myeloma cells, regardless of what chemo treatment you throw in your blood.
So, you partially knock down one clonal line with one drug (and stop well before you become refractory to that drug), and then partially knock down another clonal line with a different drug, etc. It would be like playing an endless game of "whac-a-mole".
I have no idea if what I'm saying really makes biological sense or not ... just throwing it out for discussion.
Or you wonder if doing this would instead create an equal playing ground for multiple clonal lines to all thrive in relatively equal numbers (which might not necessarily be a bad thing??). I'm thinking this might be the case with multiple myeloma, since you have the stem cells in place and at the ready to produce more multiple myeloma cells, regardless of what chemo treatment you throw in your blood.
So, you partially knock down one clonal line with one drug (and stop well before you become refractory to that drug), and then partially knock down another clonal line with a different drug, etc. It would be like playing an endless game of "whac-a-mole".
I have no idea if what I'm saying really makes biological sense or not ... just throwing it out for discussion.
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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?
Dear all,
This is a great thread. I think you all recognize the fact that this is not a black and white situation. A couple of points:
1) While the concern of breeding resistance with Revlimid maintenance is a valid one, one study after transplant shows a survival advantage and the other shows equivalent survival. As such, even if the disease that relapses after Revlimid maintenance is more difficult to treat, the improvement in disease control up to that point likely negates that effect. Thus, in one study you get equivalent survival, and in the other study you get improved survival. Additionally, there are differences between the two studies, which may account for the lack of survival advantage seen in the French study.
The bottom line is that we need more data as to how patients do with subsequent therapy after progression, for those that opt to do Revlimid maintenance and those that do not. The good news is that the treatment choices for relapsed disease have improved so greatly in the recent past, that the disease that progresses on Revlimid maintenance may not be as problematic as it was a couple of years ago.
I personally feel that Revlimid maintenance should be, at a minimum, considered for most patients. But, it is a complicated discussion, and the pros and cons of treatment must be discussed with the patient at length, such that an informed decision can be made.
2) I like Stan's idea a lot. There is a push to evaluate multi-drug maintenance therapy, but sequencing may produce the same effect with less toxicity. I think I am going to hire Stan to join our faculty!
Thanks for the great discussion!
Pete V.
This is a great thread. I think you all recognize the fact that this is not a black and white situation. A couple of points:
1) While the concern of breeding resistance with Revlimid maintenance is a valid one, one study after transplant shows a survival advantage and the other shows equivalent survival. As such, even if the disease that relapses after Revlimid maintenance is more difficult to treat, the improvement in disease control up to that point likely negates that effect. Thus, in one study you get equivalent survival, and in the other study you get improved survival. Additionally, there are differences between the two studies, which may account for the lack of survival advantage seen in the French study.
The bottom line is that we need more data as to how patients do with subsequent therapy after progression, for those that opt to do Revlimid maintenance and those that do not. The good news is that the treatment choices for relapsed disease have improved so greatly in the recent past, that the disease that progresses on Revlimid maintenance may not be as problematic as it was a couple of years ago.
I personally feel that Revlimid maintenance should be, at a minimum, considered for most patients. But, it is a complicated discussion, and the pros and cons of treatment must be discussed with the patient at length, such that an informed decision can be made.
2) I like Stan's idea a lot. There is a push to evaluate multi-drug maintenance therapy, but sequencing may produce the same effect with less toxicity. I think I am going to hire Stan to join our faculty!
Thanks for the great discussion!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
24 posts
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