Smoldering Myeloma: What Do The Latest Research Findings Mean? A Discussion With Dr. Ola Landgren
As The Beacon previously reported, Spanish researchers recently presented clinical trial results showing that active treatment may be beneficial for some smoldering multiple myeloma patients.
Specifically, the results of the study showed that high-risk smoldering multiple myeloma patients who received Revlimid plus dexamethasone followed by Revlimid maintenance had a longer time to disease progression and better overall survival than patients who did not receive treatment (see related Beacon news).
To help Beacon readers put these results into perspective and better understand their implications, The Beacon asked myeloma specialist Dr. Ola Landgren for his feedback and thoughts on the study.
The resulting discussion was wide-ranging and touched on issues of interest to all multiple myeloma patients — not just those with smoldering myeloma.
Dr. Ola Landgren, who was not involved with the Spanish study, is a Senior Investigator at the National Institutes of Health (NIH) and Chief of the Multiple Myeloma Section at the National Cancer Institute (NCI). He is regarded as an expert on monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma, and he is involved in a number of important studies into potential new treatment regimens for multiple myeloma.
The Myeloma Beacon: How significant are the findings of the Spanish research team, led by Dr. María-Victoria Mateos?
Dr. Landgren: I find the results by Mateos et al. of major importance. Their data show that treatment of high-risk smoldering multiple myeloma translates into both progression-free and overall survival benefits. These are novel insights. In my opinion, they set the stage for the development of new treatment studies for high-risk smoldering multiple myeloma, aiming to delay and/or prevent progression to multiple myeloma.
Are the findings sufficient to recommend any change in current practice in regard to the treatment of high-risk smoldering myeloma patients?
No, I don’t think so. This study is based on approximately 60 treated and 60 non-treated high-risk smoldering multiple myeloma patients. The main reason why I don’t think it is time to change clinical care is that I think we need to see the results replicated in other independent studies. This view is in full accord with that of the investigators of the Spanish study; they emphasize the need for validation.
Another reason is that, until we have better biological markers easily available to define an individual’s risk of progression to symptomatic multiple myeloma, there is a risk of over- and under-treatment of patients diagnosed with smoldering multiple myeloma.
Let me also say that, based on our completed and ongoing research, I personally do not think that smoldering myeloma truly exists as a disease entity.
I think there are patients in the so called “smoldering multiple myeloma” category that are more like patients with MGUS, while others are what I would call “early myeloma.”
This is not a perspective, however, that you will find in the textbooks (yet).
In our clinic at the NIH, we have assessed a large number of patients diagnosed as smoldering multiple myeloma, with a wide range of tools, including flow cytometry, biomarkers, microRNAs, genetic profiling, molecular / functional imaging, marrow vascularity, early bone changes, and so on. And we have learned that there is tremendous heterogeneity in terms of biology and the risk of developing symptomatic multiple myeloma.
More importantly, what we have seen is that the biological markers in so-called “high-risk smoldering myeloma” patients are very similar to those seen in patients with symptomatic multiple myeloma. This is why I would rather call high-risk smoldering myeloma “early myeloma.” The main difference is that the early myeloma patients have not (yet) developed kidney failure, bone fractures, or other symptoms.
[For more information about Dr. Landgren’s studies of precursor diseases and how they progress to active myeloma, see a related Beacon opinion article.]
What caveats do you feel are important to mention in regard to the Spanish research?
In addition to the above mentioned need for validation of the results in other studies, I think a caveat is that the study focused mainly on clinical markers. For example, additional molecular markers and functional imaging would allow a much more detailed investigation into why and how the treatment works in some patients and not in others. That would be a translational / biological approach. I am in favor of translational / biological treatment studies to maximize the possibilities to advance the field.
Of course, I realize that it boils down to resources, and I know it is very expensive to do those types of things. Also it takes a lot of advanced infrastructure. Hopefully, future studies will provide more translational / biological insights.
If you believe the Spanish research argues in favor of early treatment of high-risk smoldering myeloma patients, do you feel that the treatment regimen used in the Spanish trial is the best treatment option, or is there evidence that treatment with other agents might be as effective – or even more effective?
The brief answer is: “nobody knows at this time”. We need to design and conduct clinical treatment studies designed to answer these questions. Until we have clear answers, we can only speculate based on available knowledge.
Here is my thinking: if you buy my arguments above about “early myeloma” – that is, that high-risk smoldering myeloma is very much like symptomatic myeloma, just with less tumor burden – then you have to ask yourself: Would you treat a younger, newly diagnosed multiple myeloma patient with a Revlimid (lenalidomide) – dexamethasone (Decadron) combination followed by Revlimid maintenance only (that is, the treatment schedule used in the Spanish study)?
My standard answer would be “No.” So, why don’t we do what we typically do for symptomatic multiple myeloma with these “early myeloma patients”? Why don’t we use a three-drug combination like Revlimid, Velcade (bortezomib), and dexamethasone (Decadron), or whatever combination we believe is better?
This is why I am so excited about our newest smoldering multiple myeloma study, which will open at the NIH during the spring of 2012. It will examine a treatment regimen involving eight cycles of carfilzomib, Revlimid, and low-dose dexamethasone followed by Revlimid maintenance for a minimum of one year. We are using carfilzomib instead of Velcade in order to increase the efficacy and at the same time reduce the side effects, in particular peripheral neuropathy [a condition characterized by pain and tingling in the extremities due to nerve damage].
Let me stress again, however, the need for more studies before any of these ideas start to be considered “standard of care.”
But isn’t that quite a leap? Essentially, you are advocating taking patients the medical profession today feels shouldn’t be actively treated, and treating them with one of the more aggressive drug regimens in use for active myeloma.
Again, the brief answer is: “nobody knows at this time”. We need to design and conduct clinical treatment studies designed to answer these questions.
To me, the whole concept of ‘watch and wait’ for smoldering myeloma is a consequence of multiple factors, including the fact that, until recently, we have not had access to effective drugs with reasonable or low toxicity profiles.
Also the disease monitoring methods have been, and still are, quite limited in standard day-to-day practice.
With toxic and not very effective drugs, it was not justifiable to expose any person to therapy unless there was a compelling need – specifically, clinically active multiple myeloma.
With newer, effective, and less toxic drugs, that way of thinking has to be challenged scientifically, in my opinion. That is what we are doing as we speak.
Looking at other cancers such as early breast cancer and early prostate cancer, much more work has already been done along these lines, and improved survival outcomes have followed.
Even if we assume that high-risk smoldering myeloma is really “early” active myeloma, is it a form of active myeloma that should be treated with a three-drug regimen that includes two novel agents?
Or, to put it another way, might this “early” myeloma best be considered a relatively “low risk” form of active myeloma. And, if so, wouldn’t many myeloma specialists be more comfortable using a less aggressive approach for that kind of myeloma?
First of all, I want to stress the need for better terminology and criteria. When we talk about “high risk” in various settings, I think there is a lot of confusion and inconsistency.
For example, “high-risk multiple myeloma” is commonly used as a term for (active) myeloma patients with a poorer prognosis than the average myeloma patient.
However, just to be clear, “high-risk smoldering multiple myeloma” refers to patients at high risk of transformation from smoldering myeloma (or early myeloma) to symptomatic multiple myeloma.
As I mentioned before, I think that many high-risk smoldering myeloma patients are already myeloma (that is, “early myeloma”).
Likewise, I would like to be bold and say: High-risk multiple myeloma does not truly exist as one unique biological entity with a given outcome.
Let’s do an intellectual experiment. Let’s say if all multiple myeloma patients were treated only with bisphosphonates such as Zometa (zoledronic acid) or Aredia (pamidronate), then the outcome would be poor for everyone.
In such a scenario, one could call all forms of multiple myeloma “high risk.”
Instead, let’s assume that a drug that cures all forms of myeloma was available. All multiple myeloma patients are treated with this drug, and all are being cured.
Now, all multiple myeloma patients are “low-risk.”
This example emphasizes the obvious. “Risk” is an interaction between biology and intervention. And intervention is a variable that changes between clinicians and institutions, and it is constantly changing over time.
To me, it suggests that there is another way of looking at multiple myeloma patients currently called “high risk.” I prefer to think of these molecular subtypes of myeloma as “myelomas we have not yet figured out how to treat.”
Again, I don’t like the term “high-risk” myeloma. It think it is misleading in that it sounds like there is one subtype of myeloma that is inherently bad, and it does not respond to therapy.
That is not true. We know there are several molecular subtypes hidden in that group and they likely require different treatments for successful outcomes. We need to figure out the biological underpinnings, identify the treatment targets, and develop the right therapies for these subtypes soon!
Regarding your last question, where you assume that “early” myeloma best be considered a relatively “low risk” form of active myeloma. I don’t think there is any data to back that up; that is a theoretical assumption.
In fact, based on our ongoing research, there seem to be “early myeloma” patients with different disease biology. Consequently, as part of a clinical treatment study, I think it is reasonable to catch low disease burden and use powerful treatment strategies.
Just to be very clear; before we have these and other related answers sorted out in clinical treatment studies, in my opinion, we should not start treating early myeloma patients in standard, day-to-day practice.
Those are great points on terminology. Can you explain a bit more, though, why you feel an aggressive approach with “early myeloma” (high-risk smoldering myeloma) may turn out to make the most sense?
If we think about “early myeloma” as a state of less tumor burden, it is theoretically possible that the less aggressive disease is curable, at least in some patients, with more effective therapy, while more aggressive disease will only be controlled (converted into chronic disease) using early therapy.
If we can cure a patient with early myeloma, that would be a huge thing for us. Of course, the pros and cons of treatment have to be balanced. We cannot accept side effects that are not in accord with the projected outcome.
In the coming years, I envision that some myeloma patients will be cured and others will have extended remission. Likely, many patients will have their disease controlled, which could be viewed as a “functional cure” — similar, for example, to successfully treated hypertension.
Before we reach this point, a lot of work remains to be done. I think key future strategies will be (1) more rational therapies / drugs (precision medicine), (2) earlier start of therapy in many patients, and (3) better monitoring before, during, and after therapy.
Again, these are ideas and concepts based on our research. It is not meant to be implemented in any clinical standard-of-care setting at this time.
However, I am very optimistic about the future. We have many new clues and tools to advance the field. We will continue working hard for our patients. Our ultimate goal is to find a cure for myeloma. It is an exciting time to develop new strategies for myeloma and its precursor states!
Related Articles:
- Revlimid-Dexamethasone Combination Delays Disease Progression In Patients With Smoldering Multiple Myeloma (ASH 2011)
- Preemptive Treatment Benefits High-Risk Smoldering Myeloma Patients, Study Finds (ASH 2009)
- Bone Lesions Detected By MRI Can Predict Progression Of Smoldering Myeloma
- Research Shows No Difference Between Early And Later Treatment For Smoldering Multiple Myeloma
- Aredia Does Not Prevent Disease Progression In Smoldering Myeloma Patients
Excellent presentation on this study nuances. Thank you!
I agree that this was a very clearly presented conversation and the Beacon staff did an admirable job. I couldn’t help but noticing a minumum of 7 times where Dr. Landgren mentioned the word “cure” or “curable,” as in
“If we think about “early myeloma” as a state of less tumor burden, it is theoretically possible that the less aggressive disease is curable, at least in some patients, with more effective therapy, while more aggressive disease will only be controlled (converted into chronic disease) using early therapy.”
This is clearly different from what we normally read from other articles or comments on the subject. The answer to the curability question guides many patient’s choice of treatment, especially those of the younger ones. But unfortunately, just like almost any other topics on the disease, the curability issue is muddled to say the least.
Agreed Ben S. But the telling thing for me is that more and more leading researchers are daring to utter the word. Ken Andersen being another one. They are all still quite reticent when they dare to say the word, when I watch them in video presentations, but they are saying it and understand fully the ramifications. I find it quite hopeful, though I agree, it isn’t right now a reality, so it can indeed get muddled up in the discussion of treatment choices.
I am a patient of Dr. Landgren’s. I am in his study of the progression of myeloma from its precursor stages. I probably am a candidate for the upcoming trial due to my high risk smoldering situation. I got a lot to talk about with him in March.
(Sorry this is long … and I hope the formatting comes out looking OK …).
I agree, fascinating article! And I appreciate everyone’s responses. Like my friend Terry, I have a direct personal interest in the subject — and more particularly in the trial described by Dr. Landgren, for whom I, like Terry, have great respect as a researcher and physician. Like Ben S, I count seven mentions of something like ‘cure’, and I agree that’s somewhat of a shift relative to most MM experts’ interviews in past years but I also agree it doesn’t at all mean the curability issue is non-muddled. Similarly, like Lori, I see the cure reference made more frequently nowadays (more than 7 years ago when I was diagnosed); but I also concur that — with possibly very specific, infrequent, and somewhat risky exceptions — curability is not demonstrably a reality now, and as such it can get muddled up in the discussion of treatment choices.
To me it’s interesting for us not to read too much into researchers’ interviews lest, for example, they find the need to censor themselves in the future. So with that in mind I’ll go into “anal”-ytical mode. Regarding the seven mentions of ‘cure’, I hope anyone interested will scour the interview itself as I have (using for example a find/search command on the webpage for the partial-word “cur”), to see the context better than I’m describing here. But briefly, here’s what I see for the 7 mentions:
#1. This is in context of an “intellectual experiment” where Landgren says “let’s assume that a drug that cures …”. Landgren is not at all suggesting that this is reality now or even in the future, it’s an intellectual experiment and I think we need to allow him or anyone else to indulge in such discussion no matter how fanciful.
#2. Same context as #1.
#3. Landgren is saying IF such and such, then there’s a THEORETICAL possibility of something. Again, these are thought processes & language that researchers & others need to use in order to consider one thing or another. If they/we can’t do that, at the risk of being misinterpreted, then we’re hosed.
#4. This follows #3 but with an additional IF imposed.
#5. Landgren says “In the coming years, I envision that some myeloma patients will be cured …”. The timeframe is open — it’s plural, so a person might say 2 years, or a person might say 1,000 years or more. And it’s a vision, not necessarily even a confident expectation. Even at that, it’s for some myeloma patients, not all.
#6. This is related to #5. But it is weaker, in that it is referring to the further hypothetical POSSIBILITY of having enough future control of the disease and symptoms in some patients such that one could consider there to be “functional cure”.
#7. In this concluding remark Landgren simply refers to cure as being “our ultimate goal”. Sure, that’s more optimistic than if he said “sorry, cure is out of the question”. But I think he’s just re-stating what’s probably true for most of us, researcher or not.
My own hard-line view is that #5 is the most hopeful of the bunch, yet as you’ll see if you re-read the passage and my comment, I don’t see much to hang my hat on.
We tend to operate under a paradigm of continual improvement. Looking at trends, that’s not an unreasonable view. But there’s nothing in this universe that guarantees that science/humanity will be able to make ANY IMPROVEMENTS beyond where we are now (much less a cure). For all we know we MAY have reached the end of humanly possible advancements — or if not, our cultures may lack the political/economic will or insight to continue onward. Or even if we currently have expectations that such-and-such will be an improvement, and therefore it at least warrants testing by clinical trial, we could be wrong — we have been wrong before with various diseases etc, with disastrous consequences. As Landgren suggests, that’s largely why the standard-of-care doesn’t vector off every time there’s something worth considering, be it carfilzomib on asymptomatic patients, or something else.
All that said, to me this IS a very hopeful interview & article, and I’m pretty excited to have read it. Landgren is making really clarifying distinctions between terms that otherwise interfere with progress & communication. He’s presenting and proposing alternate views of the disease which to me seem plausible even if they need formal validation. He’s describing scientific PROCESSES that are I believe our best hope for eventually finding far better treatments, yes maybe even cures, for myeloma. He’s pointing out that while we do clinical trial research in an attempt to improve the standard of care, meanwhile our standard of care is far better than we’ve enjoyed in past years — so if I have to deal with this disease, now is an exciting time to have it compared with 7 or 20 or 50 or 1000 years ago. And he’s pointing out that although we can’t have foreknowledge of our experiments, the trajectory is such that it’s likely we’ll see great improvements in the future. I hope to be around to see what nature and science might reveal to us in future years & decades.
Hi Dr. Landgren! Thanks for the thought provoking article. I too hope that the future of this ‘treatable but not YET curable’ disease lies positively in the research being done with patients with ‘smoldering’ myeloma. Those patients are not yet caught in a dangerous time with the awful ‘CRAB’ manifestations, that make myeloma so miserable.
Many of us, myself included, went right thru the ‘smoldering’ phase without yet being diagnosed. One question that I have is, now that treatments may be more feasible to do on ‘smoldering’ patients, at what age and how frequently should one be tested for the ‘M’ protein as part of a regular medical check up?
As part of routine, annual physical checkups over my whole adult life, I have been tested for other cancers on an annual basis (such as breast…have had mammograms since age 40). Have been tested for colon cancer, and more. Had my blood tested for all the usual things and the parameters were normal. I realize that MM is just 1% of cancer diagnoses, but wouldn’t it be better for patients to know that it is developing, rather than have it hit you right out of the blue when you have some awful physical problems?
Could you please give me a considered answer to this (at what age and how frequently)… and I will write a letter to whoever I think would be responsive here in our health care system. Also, what percentage of patients with MGUS go on to develop ‘smouldering’ and full fledged MM? Thanks so much.
Dr. L,
Have you given consideration to adding an arm or arms with some of the non-patented remedies that appear to have efficacy in holding patients in the smoldering category? Low cost, numerous willing subjects available instantly.
You could study curcumin (see Aggarwal, M.D. Anderson, and others) on smoldering, mgus, and CR patients instead of maintenance. Curcumin, for example, already has GRAS status from the FDA (generally recognized as safe).
Hopefully your research isn’t totally tied to money from drug companies whose only interest is the use of their own produicts. Myeloma patients of all stripes are depending on the scientific community to take a serious look at things that may not be patent-able. At this time all we hear is “well, there aren’t studies to back this up, so take Major Manufacturer’s drug instead.”
There are many – many – patients available for studies on curcumin and similar therapies. Instantly available. Why overlook it and concentrate solely on the most potent side effects and costly therapies?
-Julie in Iowa
I think this is a great interview and I appreciate Dr. Landgren taking the time to share his thoughts with us.
Regarding the comment just made by Julie Zimmer, I think Dr. Landgren makes it clear that, if something is myeloma — “early” or not — he thinks it’s best to treat it relatively aggressively. So I doubt he would see the sense in testing something like curcumin as a potential treatment when there are other treatments which have had a clear role in myeloma patients living longer today than they did 10 years ago.
For Dr. Landgren, treating “early” myeloma with curcumin probably would be like “bringing a pop gun to a gun fight.”
The other thing that I think is important to mention is that Dr. Landgren works for the NIH. If I’m not mistaken, NIH studies are funded solely by the government. NIH employees also are tightly restricted in terms of what sort of funds they can accept (if any) from pharmaceutical companies or other private companies.
The same can’t be said about most university researchers, who can make lots of money consulting for, or carrying out research funded by, pharmaceutical companies.
But that really isn’t true for NIH employees.
So comments like “Hopefully your research isn’t totally tied to money from drug companies” are not only impolite, they disregard where Dr. Landgren works and what that shows about his motivations.
As a patient of Dr. Landgren’s, I can attest to the fact that he has never, ever pressured me into any clinical trials. In fact, he admitted me into his study without treatment as a smolderer. Another so-called expert doctor was already sizing me up for an allogeneic SCT last year. I believe he has no agenda whatsever other than the well-being of his patients. He has always been absolutely transparent with me in every single aspect of his care. He never has to disclose any conflicts of interest because frankly he doen’t have any. I am sure I speak for many of his patients who are readers and posters here. Getting the myeloma diagnosis was devastating for me and my family. Finding Dr. Landgren was a godsend and I believe I am in the ablest hands in his care. He is not motivated by commercial interests but by a desire to beat this damn disease and for a man of his high intelligence and education, he is very humble and compassionate.
First, I like the way Dr. Landgren talks about smoldering myleloma as early myeloma. It’s always bothered me to think of smoldering myeloma as something different then active myeloma – it’s just not as active. I tend to think that after someone has the disease, it progresses very slowly as it tries to take hold within the body, but at some point it reaches critical mass and takes off.
Secondly, I like that he questions the traditionally held concepts of high and low risk myeloma. How can we categorize something as complex as this disease and how it interacts with our DNA into two simple categories, particularly given our limited knowledge in this area.
Finally, if you agree with his assertion that smoldering myeloma is early myeloma, doesn’t it make sense to treat it right away as he suggests (I think that would be my approach). This gets back to the idea that it needs to reach critical mass to really take of and start causing the symptoms assoiciated with it. If you can hit it before then, it’s not as strong, and I would think you could significantly delay it onset.
Think of the cancer as a binomial progression, replicating from a single cell (i.e., 1,2,4,8,16,32,64..). You probably need to get into the billions or more before symptons occur, but by that time, it has a strong foothold. If you could disrupt it while the number of cells is considerably less, you considerably slow (or perhaps even stop) the progression.
I don’t really have any scientific justification for this reasoning, it’s more my way of thinking with my engineering and mathematics background.
Terry is right on! I have recently spoke to Dr Landgren and he is Amazing. I am hoping to visit him soon and get some straight answers. I too was “sized up” by a so called expert for a combination auto/allo transplant. All this is tough enough and to then meet someone you are supposedly able to trust and see that they are possibly trying to take advantage of your situation is unspeakable. Dr Landgren is a class act and a Gentleman. I am counting the days until I hear back from his team and make an appt. I know this is a bit off topic but, anyone that questions Dr Landgrens motives clearly has never spoke to him. Thanks Terry! its because of you that I called him!!!!!
I agree with Kevin J that if we are talking about early myeloma, then treating it early may make the most sense.
This is particularly so, if — as Dr. Landgren indicates — the therapy is of low toxicity.
And it would be even more so, if such early therapy held the promise of longer overall survival along with high quality of life. Maybe this will be the case with the newer agents like Carfilzomib used in the Landgren study. I don’t think it has been the case with earlier combinations of agents.
I forgot to mention: Dr. Landgren also points out that some SMM patients are really MGUS patients (for which no treatment is warranted). But as far as I can tell, we still don’t have accurate diagnostic tools for distinguishing between the MGUS and early myeloma versiosn of SMM.
I am 70 years old and was diagnosed with Smoldering Multiple Myeloma 15 months ago. To date I have received no treatment (and quite frankly I’m not eager to start). Is there an outline of Dr Landgren’s diagnostic and monitoring tests that he normally performs on patients? Also is Dr Landgren or staff availabe to consult with my Hematologist/Oncologist in Bend, Or?
Thanks for your input. Bob Davis
Lori, Bruce,
I think the issue of using the word cure has more to do with the nature of myeloma and our current testing techniques. Myeloma is a “patchy” disease. Tests like PET, MRI, 24 hour urine, bone marrow biopsies, PCR, etc are used, but none is a definitive test. When I try to explain what remission in myeloma means to friends, I always tell them I had the most sensitive tests done and the myeloma could not be found but that does not mean it is not there. There are subgroups of patients that have a very low chance of relapse, but no doctor that I have ever seen says publicly, with 100% certainty, that a particular patient will never relapse.
Mark
Terry, Art,
I am really surprised to hear you characterize doctors that use allos as “so-called experts”. Allogeneic transplantation is considered by most doctors as the only current therapy that can potentially cure myeloma patients. The families of patients that do allos are just as devastated by their diagnosis as both of your families were.
Remember when you see studies showing 30-40% of patients that have never relapsed after doing allos as part of their upfront therapy are real people. I am sure they have the same great respect for their doctor as I do for mine. My doctor is quite capable of writing prescriptions for Revlimid, Velcade, etc. Judging from my experience of coming out of my allo with a molecular response and having no problem with GVHD, she also has great skill in applying allogeneic transplantation. I also have am very confident I will live a long, healthy life. I think doctors that attempt to give their patients the longest, drug free remissions possible should be applauded, not trashed.
Mark
Hi Mark, you make great points in your most recent post—and all of your other ones for that matter. I did not mean to disparage doctors who do allos or the procedure itself. I apologize to you and any others for any unintentional offense. In fact, one of my two doctors performs them successfully. My gripe was with a particular doctor, who will remain nameless, who brought up doing an allo in the first five minutes of our meeting. He was aggressive, curt, clearly hadn’t read my file thoroughly and seemed not used to being questioned by a mere mortal. I had to travel a great distance to meet with him and my insurance was billed quite a lot for what, I believe, amounted to an inadequate evaluation. Two other MM experts at different hospitals during the same time frame (August, 2011) found that I was in fact smoldering and not in need of any treatment.
Hello.
Thank you Dr. Landgren for your informative article. Having been in healthcare for 30 plus years, your logic makes sense to me.
I understand very little of the complex spectrum of hetergenous abnormalities that comprise myeloma. I am thankful for researchers, such as yourself, who are working to dissect and understand this disease.
The early diagnosis, treatment, cure or control of any adverse health condition, before it becomes detrimental, is worthwhile. I am a diabetic educator and have found that educating or treating the “pre” diabetic is more beneficial for the patient than waiting to treat the complications of diabetes.
My example is oversimplified, but makes the point that most illnesses, cancer included, progress on a continuum. The rate that they progress is dependant on multiple factors. Your statement regarding tumor burden in smoldering (early) myeloma essentially reflects that the contiuum that myeloma progresses along is based on tumor load.
The challenge is to classify what causes some smoldering patient’s tumor load to progress more rapidly than others. These are the people who may potentially benefit from the risk involved in early treatment, over watchful waiting.
I have what is at present termed, “high-risk” smoldering myeloma and am in the NIH observation study. I may at some point consider enrolling in a treatment clinical trial. I am not anxious to do so, but if the lab values keep moving in the wrong direction, I feel fortunate to have an option.
Terry,
Thanks for the clarification. I also wanted to mention something you may find useful. I had mentioned to you in another post (in another thread) that I had used Velcade/Doxil/Dex as my Induction and had very good results. I had suggested it may be helpful for a patient long term if they did not use both an IMID and a proteasome inhibitor as Induction. There is a great slide on Page 8 of this presentation by Dr. Durie of the IMF that compares the efficiency of different Induction regimes. Note Velcade/Cytoxan/Dex performs just as well as Velcade/Revlimid/Dex. Also interesting to note that Velcade/Cytoxan/Revlimid/Dex does not show much improvement over either 3 drug combo.
http://myeloma.org/pdfs/Best-of-ASH-2011_01-25-12.pdf
Another great slide is on Page 16. Look at how much more sensitive Immunophenotypic and Molecular Responses are compared to CR with negative Immunofixation. I have pointed out how valuable these levels of responses are in the Allo setting. It would be great if more research was done in the non-Allo setting using these tests. The Beacon reported on a European study from last year that showed the benefit of attaing a Molecular response in the non-Allo setting.
http://www.myelomabeacon.com/news/2010/04/06/velcade-thalidomide-dexamethasone-therapy-after-stem-cell-transplant-improves-response-in-multiple-myeloma-patients/
Hope these are helpful to you.
Mark
Mark,
thanks for those great slides.
Mark
I have to once again concur with Terry. I am sorry if I was not specific but this was also a bad experience. The Dr was in an obvious rush to finish with me (i was his first appt. at 7 am) He stated in his dictation that he examined me when in fact he never even touched me. And in his report reported on my physical conditions when there is no way he could know any of these. He had not even read over my records until he got into exam room and was more interested in telling me how he could “cure” me than listening to my concerns and answering my questions. So all in all I just had a bad experience and he was someone who came highly regarded and is supposed to be an “expert” maybe i caught him on a bad day. But, it was more about him than me. So maybe I should have billed him $450 for the 1/2 hr. I was there.
I do appreciate your point and agree with you. I am glad you have a wonderful physician and wish you the best.
Art
With respect to Mark’s comments about allos, I am not familiar with the observation that 30-40 percent of such patients have never relapsed. How long out has this been examined? I certainly recall that a high fraction of allo patients die as a result of the procedure or have life-time issues with host versus graft rejection.
I have also heard from my oncologist that 50 percent of patients remain in remission 8 years after VRD therapy and a standard autologous transplant.
Art,
No problem – just wanted to mention that all of them are not evil. I did read your Introductory post in the forum and I did find it strange that a Doctor was not sure if you were active or smoldering but made the great leap to assessing you as High Risk and recommendeding an Allo transplant. I did one because I thought it was best for me – it certainly is not a procedure that that should be “pushed” on a patient. You also mentioned that the other Doctor did not think a PET scan was necessary – I would not be comfortable with that Doctor either.
I think you made a great decision going to see Dr. Landgren. I have only read great things about him. It was also mentioned above that he has no Conflicts of Interest on his research papers. I always check that after I read anything a Doctor writes. I personally have no interest in being treated by a Doctor that is a paid consultant or sits on a Board of Directors of a Drug company. That eliminates many of the well known treating facilities but I am very happy with my decison.
Good luck with everything,
Mark
Eb,
Hope you are doing well. With all due respect to your Oncologist, I have never read a study that shows 50% of patients that do VRD and than do an Auto get 8 years of continuos remission. If anyone can show me some research that shows this, please post it here. This comes right off the IMF website with respect to Auto transplants:
Q Can I relapse after a transplant?
A Yes. Unfortunately, the majority (at least 50%) of all multiple myeloma patients relapsed 18 to 36 months after their transplant was completed.
http://myeloma.org/ArticlePage.action?articleId=40
With respect to Allo transplants, I have posted many links in the forums with regard to current research about them. My experience with it has been a positive one so far. Treatment Related Mortality is typically between 10-14% in current studies using a Tandem Auto-Allo RIC approach. Graft vs Host disease is controlled in a majority of patients when ATG is used prior to transplant. Allos are far from a perfect form of therapy in Myeloma and they are not appropriate for many patients. Just like Myeloma therapy in general, there have been great strides made in Allo transplantation and much more improvement is necessary.
Good luck and hopefully you will be in that group of patients that enjoy a long Remission.
Mark
Hi Mark
Well I had never heard of such great results following VRD treatment and an ASCT either. But this is what my oncologist – supposedly the local expert — asserted for his patients. But he may have been bull-shi##ing me or engaging in a post-hoc whitewashing of his results. He clearly was someone who likes to give drugs as soon as possible; in my case, he was scheduling infusions the following week without even establishing my baseline condition.
So in fact, he no longer is my oncologist for a number of reasons. I am not a cell biology experiment — even if I am largely screwed. So I will be looking carefully into the studies you mention.
Thanks
Although just to defend my former oncologist: What about the greater to 50 percent of patients that did NOT relapse within 36 months after an ASCT. And more importantly, to what extent are these data based on the latest– and apparenty superior — front line treatments such as VRD?
After reading all the comments made by leading Oncologists concerning Smoldering Myeloma, which I have, I am still confused about this disease. Is Monoclonal Gammopathy of Uudetermined Significance more serious than MGUS? I haven’t been told by my Oncologist, yet, which type I have. I’m not being treated, so far, just getting blood tests and urine tests every 2-3 months.Should I undergo treatment of some type at this early stage? Should I be on a special diet? Should I be working out to strengthen my body?I walk 4 miles every day, is this doing any good for my diagnosis? I’m 74 years old and very concerned about my health. My family doctor thinks the reason I have Smoldering Myeloma is because I sprayed Herbicides (Agent Orange)from a helicopter, when I was in my 20′s and 30′s, for 14 years. Could this be the cause? Please answer my questions since I need to know. Thank You!!!
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