Multibilly: I have read the full text and want to thank you for posting this information. You are an amazing source of information and have earned the respect of not just myself and numerous other fellow posters, but also the good doctors who volunteer their services to the Forum.
While I found the article really informative, because it is good to know that the matter of maintenance is not so cut and dry, I am once again sadly convinced that much of the proper treatment of myeloma remains quite a mystery and that one can only hope that the trust we place in our doctors is justified. This is not to say that our doctors are not competent and knowledgeable. It is just a somber recognition that they, too, are limited in knowing what best to do.
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Re: What is "maintenance therapy" and how is it determined?
I agree with Mrozdav -- that's a very useful article, Multibilly. Not to take away from what Dr. Berenson wrote, but I found the part by Drs. Vesole and Siegel to be particularly interesting, and I gained a lot of respect for them after reading what they wrote.
Keep in mind that, if I'm not mistaken, both Drs. Vesole and Siegel started their careers at UAMS, and UAMS for ages has advocated intensive, lengthy therapy for myeloma, involving combination therapy with a zillion drugs up front, tandem transplantation, and a couple of years of maintenance therapy.
Yet here Drs. Vesole and Siegel are saying that the evidence in favor of maintenance therapy is sketchy, at best.
And, heck, just to add some spice to the discussion, they even throw in a swipe at the usual assumption that Revlimid is a better drug than thalidomide.
I would say they've earned some kudos, even if you don't necessarily agree with them.
Keep in mind that, if I'm not mistaken, both Drs. Vesole and Siegel started their careers at UAMS, and UAMS for ages has advocated intensive, lengthy therapy for myeloma, involving combination therapy with a zillion drugs up front, tandem transplantation, and a couple of years of maintenance therapy.
Yet here Drs. Vesole and Siegel are saying that the evidence in favor of maintenance therapy is sketchy, at best.
And, heck, just to add some spice to the discussion, they even throw in a swipe at the usual assumption that Revlimid is a better drug than thalidomide.
I would say they've earned some kudos, even if you don't necessarily agree with them.
Re: What is "maintenance therapy" and how is it determined?
Maintenance agents are typically administered at lower doses or less frequently than therapeutic doses, or in combination with corticosteroids. For instance, bortezomib is given every other week instead of 4 times monthly and IMiDs are continued along with corticosteroids if corticosteroids were part of the patient’s treatment regimen."
It is really surprising a doctor would advocate long term use of steroids knowing the side effects, especially bone thinning, for myeloma patients.
Side effects of oral corticosteroids
Because oral corticosteroids affect your entire body instead of just a particular area, this form is the most likely to cause significant side effects. Side effects depend on the dose of medication you receive and may include:When taking oral corticosteroids longer term, you may experience:
- Elevated pressure in the eyes (glaucoma)
- Fluid retention, causing swelling in your lower legs
- Increased blood pressure
- Mood swings
- Weight gain, with fat deposits in your abdomen, face and the back of your neck
Source: http://www.mayoclinic.org/steroids/art-20045692?pg=2
- Clouding of the lens in one or both eyes (cataracts)
- High blood sugar, which can trigger or worsen diabetes
- Increased risk of infections
- Thinning bones (osteoporosis) and fractures
- Suppressed adrenal gland hormone production
- Thin skin, easy bruising and slower wound healing"
Fortunately I only needed 4 cycles of dex with my induction and I have used no steroids since. I am definitely fortunate to have a doctor that is concerned about her patients long term quality of life.
Mark
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Mark11
Re: What is "maintenance therapy" and how is it determined?
Treatment of myeloma has not been systematically developed. In part that might have been difficult 25 years ago when knowledge about cytogenetics and gene expression profiling and the individual nature of myeloma as a clonal and heterogenous disease were not explicated.
So what we have had is a somewhat topsy turvy let's-try-this approach that has developed with more recent clinical trials. The pharmaceutcal companies, either directly or through accident, found a drug they formulated and tested worked with plasma cell dyscrasias in humans. Animal and cell laboratory studies of 'models' of the disease and understanding of its cellular biology characteristics have all contributed over time.
I doubt many of the doctors treating us really get to grips with the wealth of scientific studies, beyond applying information from their small clinics and clinical trials to treat their patients. But when I look at the publications under the term "multiple myeloma", it becomes clear that the very heterogenous nature of multiple myeloma means studies are not equivalent in terms of the patient populations or sizes of samples, especially now we know the importance of genetics.
Also, drug regimens have not been systematically studied as head-to-head studies with dose titrations, e.g., to allow for e.g. bone size / body weight , age, fitness at baseline, etc, of patients. So giving the same dose of a drug to people of two different people may well elicit different responses, cytogenetics aside. The rarity of new myeloma patients means numbers for prospective studies are small unless clinial centres collaborate to work together.
I am beginning to realise now why people may get such divergent responses to the same treatments, not entirely cytogenetics linked. There is much that is purely guesswork, but from a haem-oncologists perspective, if a trial shows benefit for multiple myeloma patients, that is what he/she will usually apply in practice. People tend to not question whether a drug is needed or indeed if it could cause more problems. Those who see many many more patients may be more questioning and see the use of myeloma trials information to be a part of the bigger picture when deciding on drug regimens and the dosages to apply to each patient.
A thought ... Drug companies will have no interest in a cure for multiple myeloma, as their revenues will dry up. So we need the clinical researchers who do not just use existing drug regimens to do the research for a cure. That is a tall order and needs clinical scientists who can see the bigger picture and apply it.. But with such polarising positions on the treatment of multiple myeloma, are we going to get the medical science needed for a cure?
So what we have had is a somewhat topsy turvy let's-try-this approach that has developed with more recent clinical trials. The pharmaceutcal companies, either directly or through accident, found a drug they formulated and tested worked with plasma cell dyscrasias in humans. Animal and cell laboratory studies of 'models' of the disease and understanding of its cellular biology characteristics have all contributed over time.
I doubt many of the doctors treating us really get to grips with the wealth of scientific studies, beyond applying information from their small clinics and clinical trials to treat their patients. But when I look at the publications under the term "multiple myeloma", it becomes clear that the very heterogenous nature of multiple myeloma means studies are not equivalent in terms of the patient populations or sizes of samples, especially now we know the importance of genetics.
Also, drug regimens have not been systematically studied as head-to-head studies with dose titrations, e.g., to allow for e.g. bone size / body weight , age, fitness at baseline, etc, of patients. So giving the same dose of a drug to people of two different people may well elicit different responses, cytogenetics aside. The rarity of new myeloma patients means numbers for prospective studies are small unless clinial centres collaborate to work together.
I am beginning to realise now why people may get such divergent responses to the same treatments, not entirely cytogenetics linked. There is much that is purely guesswork, but from a haem-oncologists perspective, if a trial shows benefit for multiple myeloma patients, that is what he/she will usually apply in practice. People tend to not question whether a drug is needed or indeed if it could cause more problems. Those who see many many more patients may be more questioning and see the use of myeloma trials information to be a part of the bigger picture when deciding on drug regimens and the dosages to apply to each patient.
A thought ... Drug companies will have no interest in a cure for multiple myeloma, as their revenues will dry up. So we need the clinical researchers who do not just use existing drug regimens to do the research for a cure. That is a tall order and needs clinical scientists who can see the bigger picture and apply it.. But with such polarising positions on the treatment of multiple myeloma, are we going to get the medical science needed for a cure?
Re: What is "maintenance therapy" and how is it determined?
Mark11 wrote:
Hello Mark,
I suspect that your "surprise" in this comment is just another example of your taking advantage of every possible opportunity you can find to take a swipe at Dr. Berenson and anyone who is sympathetic to his views. I say that because I don't believe someone as well informed about myeloma-related research would really be "surprised" at a myeloma specialist recommending long-term steroid therapy.
I am not a patient of Dr. Berenson, and I also believe his views on transplantation are an outlier among those of leading myeloma specialists. I also have my doubts about the value of maintenance and other forms of "continuous" therapy for myeloma.
That said, there is plenty of peer-reviewed research suggesting that including a steroid in the long-term treatment of myeloma patients can provide at least a progression-free survival benefit, if not an overall survival benefit. Here is just a smattering of Beacon articles about such research that show up on the first page of a quick Google search:
"Continuous Revlimid-Dexamethasone Therapy Delays Progression And Improves Survival In Older Newly Diagnosed Myeloma Patients (ASH 2013)," The Myeloma Beacon, Feb 3, 2014
"Extended Use Of Revlimid Plus Dexamethasone Delays Progression Of Relapsed / Refractory Myeloma," The Myeloma Beacon, Oct 4, 2013
"Study Finds Revlimid-Dexamethasone Is Effective And Safe For Relapsed/Refractory Myeloma In ‘The Real World’", The Myeloma Beacon, Sep 6, 2013.
I also suspect the Mayo Clinic summary that you quote is aimed more at long-term use of steroids in cases such as the treatment of pulmonary and skin conditions, where such use can extend over decades, rather than the time frames more relevant to myeloma patients.
I truly value the many contributions you have made, and I hope will continue to make, here in the forum. But I, for one, could do without the sarcasm and disrespect that seem increasingly to be working their way into your postings.
It is really surprising a doctor would advocate long term use of steroids knowing the side effects, especially bone thinning, for myeloma patients.
Hello Mark,
I suspect that your "surprise" in this comment is just another example of your taking advantage of every possible opportunity you can find to take a swipe at Dr. Berenson and anyone who is sympathetic to his views. I say that because I don't believe someone as well informed about myeloma-related research would really be "surprised" at a myeloma specialist recommending long-term steroid therapy.
I am not a patient of Dr. Berenson, and I also believe his views on transplantation are an outlier among those of leading myeloma specialists. I also have my doubts about the value of maintenance and other forms of "continuous" therapy for myeloma.
That said, there is plenty of peer-reviewed research suggesting that including a steroid in the long-term treatment of myeloma patients can provide at least a progression-free survival benefit, if not an overall survival benefit. Here is just a smattering of Beacon articles about such research that show up on the first page of a quick Google search:
"Continuous Revlimid-Dexamethasone Therapy Delays Progression And Improves Survival In Older Newly Diagnosed Myeloma Patients (ASH 2013)," The Myeloma Beacon, Feb 3, 2014
"Extended Use Of Revlimid Plus Dexamethasone Delays Progression Of Relapsed / Refractory Myeloma," The Myeloma Beacon, Oct 4, 2013
"Study Finds Revlimid-Dexamethasone Is Effective And Safe For Relapsed/Refractory Myeloma In ‘The Real World’", The Myeloma Beacon, Sep 6, 2013.
I also suspect the Mayo Clinic summary that you quote is aimed more at long-term use of steroids in cases such as the treatment of pulmonary and skin conditions, where such use can extend over decades, rather than the time frames more relevant to myeloma patients.
I truly value the many contributions you have made, and I hope will continue to make, here in the forum. But I, for one, could do without the sarcasm and disrespect that seem increasingly to be working their way into your postings.
Re: What is "maintenance therapy" and how is it determined?
Hi Ian,
I hope all is well with you today.
You wrote:
This is a thread about maintenance therapy after a patients first line therapy. Lets see what the IMWG Consensus Statement says about steroid use for maintenance.
"Swipe", or going by what the available data tells us with respect to use of steroids for maintenance?
I am not going to use the "T" word or discuss Dr. Berenson in this thread. There are other threads devoted to those topics in the Forum.
Two of the links you quote refer to relapsed / refractory therapy and are therefore not relevant to the discussion in this thread. The FIRST trial shows a statistically insignificant increase in Overall Survival (59 vs 56 at 4 years) and 5 extra months of PFS for continuous Revlimid / dex vs. Revlimid / dex for 18 months. How much of that 5 months of PFS is contributed to the dex as opposed to Revlimid? I have no idea and I do not think it provides evidence that dex or steroids as maintenance is necessary or worth the additional side effects. Everyone knows that Revlimid maintenance increases progression-free survival (PFS), but rarely shows an overall survival (OS) advantage. This study seems in line with what we discussed in previous posts.
Mark
I hope all is well with you today.
You wrote:
"I suspect that your "surprise" in this comment is just another example of your taking advantage of every possible opportunity you can find to take a swipe at Dr. Berenson and anyone who is sympathetic to his views."
This is a thread about maintenance therapy after a patients first line therapy. Lets see what the IMWG Consensus Statement says about steroid use for maintenance.
"Glucocorticosteroids have significant activity in myeloma as single agents13 and induce additive or synergistic activity in combination with other drugs.14 Berenson et al showed a significant increase in remission duration and in survival with 50 mg prednisone every other day compared with 10 mg every other day,7 but in another study with single-agent dexamethasone (40 mg days 1-4, every 28 days), no benefit was observed.8 A comparison of dexamethasone with interferon maintenance treatment showed similar remission durations, but more relapsing patients could be reinduced with melphalan-dexamethasone after interferon maintenance therapy than after dexamethasone.9 Taken together, the available evidence is insufficient for recommending corticosteroid maintenance therapy."
"Lenalidomide is an attractive drug for maintenance therapy with the advantage of oral administration. It was found to be particularly active in patients with high IRF4 expression34 and with higher cereblon expression.35 Dexamethasone enhances the antimyeloma effect of lenalidomide but antagonizes the immunostimulatory effects in a dose-dependent manner.36 Hence, single-agent lenalidomide seems to be the logical choice for maintenance treatment when tumor load has already been reduced significantly and control of the residual tumor cells by active immune surveillance is the clinically relevant priority."
Source: H Ludwig et al, "IMWG consensus on maintenance therapy in multiple myeloma," Blood, Mar 29, 2012 (link to full text of article)
Related Beacon news article: "Experts Publish Consensus Statement On Maintenance Therapy In Multiple Myeloma," The Myeloma Beacon, Feb 1, 2012.
"Swipe", or going by what the available data tells us with respect to use of steroids for maintenance?
"I am not a patient of Dr. Berenson, and I also believe his views on transplantation are an outlier among those of leading myeloma specialists."
I am not going to use the "T" word or discuss Dr. Berenson in this thread. There are other threads devoted to those topics in the Forum.
Two of the links you quote refer to relapsed / refractory therapy and are therefore not relevant to the discussion in this thread. The FIRST trial shows a statistically insignificant increase in Overall Survival (59 vs 56 at 4 years) and 5 extra months of PFS for continuous Revlimid / dex vs. Revlimid / dex for 18 months. How much of that 5 months of PFS is contributed to the dex as opposed to Revlimid? I have no idea and I do not think it provides evidence that dex or steroids as maintenance is necessary or worth the additional side effects. Everyone knows that Revlimid maintenance increases progression-free survival (PFS), but rarely shows an overall survival (OS) advantage. This study seems in line with what we discussed in previous posts.
Mark
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Mark11
Re: What is "maintenance therapy" and how is it determined?
Hi Edna,
Thanks for the excellent post. That is why I try and get patients to read the peer reviewed papers and not just accept the authors interpretation of the results.
Mark
Thanks for the excellent post. That is why I try and get patients to read the peer reviewed papers and not just accept the authors interpretation of the results.
Mark
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Mark11
Re: What is "maintenance therapy" and how is it determined?
Hi Mark,
In my previous life, I was a relevant scientist and peer reviewed papers for publication. I am more sceptical than you from my experience of what is published. One needs to see a detailed systematic review stating the evidence levels used to choose studies for inclusion when assessing a drug regimen. This is rather missing IMHO.
You may want to get patients to read 'peer reviewed papers', but they need to have the knowledge and skills to interpret and question what they read. That is why people use this forum, which allows them to have the views of experts in the uncertain clinical treatment of this disease without having to become experts themselves.
In my previous life, I was a relevant scientist and peer reviewed papers for publication. I am more sceptical than you from my experience of what is published. One needs to see a detailed systematic review stating the evidence levels used to choose studies for inclusion when assessing a drug regimen. This is rather missing IMHO.
You may want to get patients to read 'peer reviewed papers', but they need to have the knowledge and skills to interpret and question what they read. That is why people use this forum, which allows them to have the views of experts in the uncertain clinical treatment of this disease without having to become experts themselves.
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