How I treat multiple myeloma in younger patients…

At the end of my December 17 2009 post, I mentioned a study that I was reading. It is titled “How I treat multiple myeloma in younger patients” and was published in “Blood” in October 2009. It doesn’t have an abstract, but here is the link: (By the way, many thanks to Sherlock for sending me the full study…)

Before we begin, let me just say that there now seems to be a trend against treating stable smoldering patients too early. Last fall, for example, I heard Dr. Durie speak of the potential dangers of prematurely treating stable asymptomatic patients, and this is confirmed by the authors of the above-mentioned study, three well-known MM specialists who, incidentally, openly declare their general propensity for very aggressive treatments in the case of younger myeloma patients (=full-blown MM, not SMM, patients, mind you). 

I thought that the following paragraph was rather extraordinary, especially when you consider that these three specialists do not believe in “saving drugs for later” but prefer, whenever possible, the gung-ho “throw everything but the kitchen sink” approach: Although the activity of novel agents has advanced to the point that early interventions are now being explored in clinical trials for smoldering myeloma, there is still no evidence that early treatment will improve survival in asymptomatic and biochemically stable patients. A critical point is that up to 25% of smoldering myeloma patients will not require active treatment for 10 to 15 years, although the majority will in fact progress during that time.

As far as I am concerned, the key point in this paragraph is: […] there is still no evidence that early treatment will improve survival in asymptomatic and biochemically stable patients. But what about that “critical point,” indicating that the majority of SMM patients will progress to active MM within 10-15 years? On what is that statement based?

Well, it turns out to be based on the 2007 New England Journal of Medicine study that we have already discussed here (see my Page titled “SMM-MM risk of progression” on the right-hand side of this page). If you would like to see the full NEJM study, click here:

Without repeating what has already been discussed on my blog, I would like to go over a few points:

1. the NEJM study looked only at 276 smolderers, which is hardly a huge number, when you consider how many smolderers there must be…on a world scale, that is.

2. the average age of this group of SMM patients at the time of diagnosis was 64 (the range was 26 – 90). Now, while I have the utmost respect for the person or people who was/were 90 years old (at the time of diagnosis), I would have liked to have seen some data on the younger patients, for example the eight patients (3%) who were younger than 40. What has happened to them? Have they progressed to active myeloma? No such data is provided.

3. the risk of progression to myeloma, according to the Mayo study, is approximately 10% per year in the first five years…let me emphasize the adverb: APPROXIMATELY. That percentage goes down to APPROXIMATELY 3% per year in the next five years, then to APPROXIMATELY 1% per year after ten smoldering years. These percentages, therefore, should be taken for what they are: estimates…nothing more…

Now for my own conclusions. A sweeping statement similar to “most SMM patients will progress to MM within 15 years” and based on a sample of only 276 people is simply astounding. Unacceptable, in my view. Nobody, with the possible exception of Harry Potter, has the ability to predict that most of us, those taking curcumin, those taking resveratrol, those on the Gerson protocol, those laughing at comedies all day, those climbing mountains, etc. etc. etc., will progress some day to active myeloma…there are just too many variables involved (and I didn’t even mention DNA…!).

Back to the “Blood” study…Even though, I repeat, the three authors favour extremely aggressive myeloma treatments, they do point out that The clinician should therefore avoid treating asymptomatic and biochemically stable patients with active therapy, allowing current drug development efforts to mature to their maximal efficacy at a time when systemic treatment does become a necessity. Indeed, early intervention may only serve to identify those patients at early risk for progression, or worse, theoretically to select out more aggressive genetic subclones of myeloma.

Now, the underlined (by me, of course) bit is not the most comprehensible string of words ever written in the English language, but I think it means that early intervention might turn a not-so-aggressive type of myeloma into an aggressive type. This happened to a couple of friends of mine…and, in fact, it could easily have happened to me: when my former haematologist advised me to begin chemotherapy in the fall of 2005, I declined (based on a gut feeling) and sought the opinion of three well-known MM specialists who confirmed that I had done the right thing, that I was still in the “watch and wait, no CRAB symptoms” category. Let us never underestimate the importance of getting a second, even third (etc.), medical opinion…!

Sorry for going off on a tangent. From now on I will try to stick to the study. It’s just that I have strong opinions…in case you hadn’t noticed! 😉

The authors also say that smoldering patients should be carefully monitored. I couldn’t agree more. In fact, if I were a biologist and had a lab in my cellar, I would be monitoring my blood almost daily!

Which tests do they recommend for newly diagnosed myeloma patients? Well, in addition to the classical CRAB measurements of calcium, renal function, haemoglobin level, and skeletal survey, the Beta 2-microglobulin, albumin and lactate dehydrogenase (LDH) should be measured, as these latter tests impart prognostic significance. Investigations for the monoclonal protein (M) require both serum and urine (24 hour) samples and today could include the serum free light chain (sFLC) assay, which has become mandatory in non-secretory or oligosecretory MM and is often the first marker of response and progression. SFLC is also of value in solitary plasmacytoma, amyloidosis and in initial evaluation of MGUS to predict risk of progression to symptomatic MM.

They also recommend having a bone marrow biopsy to check for any abnormalities that would put the patient into a high-risk category.

And here is another important point: although the conventional skeletal survey remains the standard method for evaluation of bone lesions, magnetic resonance imaging (MRI) is more sensitive and is recommended to exclude spinal cord compression, soft tissue mass in a localized painful area or for assessing BM involvement in patients with solitary plasmacytoma and smouldering myeloma. The role of PET-CT is less well defined in MM, but can be useful for detecting extramedullary disease, unsuspected bone lesions and evaluating patients with plasmacytoma as well as non or oligo-secretory MM.

Quick aside (sorry, can’t help it!): after reading the vitamin D and myeloma study (see my Page on “Myeloma and vitamin D”), I am absolutely convinced that we should all have this simple test done on a routine basis…regardless of our stage (MGUS, SMM or MM). Please add it to your list.  

At any rate, these are the parts of the study dealing with asymptomatic (smoldering) myeloma. The rest focuses on ASCTs and on the authors’ personal predilection for aggressive treatments, via the use of multiple chemo drugs…especially with younger patients who are able to tolerate toxicities and pursue high dose therapy approaches. If my myeloma were to turn aggressive some day, I suppose I might consider such an approach. But for now my goal is to keep the tiger dormant…(see:

P.S. Curiosity: since the authors of this study were more than one, shouldn’t the title have been “How we treat multiple myeloma in younger patients”? Hmmm…


  1. dear margeret, i’m with 38 years freshly diagnosed with high risk mgus and till 3 weeks i’m a great fan of your blog. it helped me (and my family (my wonderful wife, my childern 2 months, 2 years and 4years old) to deal better with the threatening depression and provides me with interesting facts, e.g. the hesperitin comment. this blog is really great work and shows a brilliant and strong authorship. thank you for it 🙂

  2. Hi Margaret
    Your blog came just in time to cheer me up, was related to my onc experience this week. My onc only does my tests once a year and just had them done. I was ecstatic all numbers went up very little, less than any years before, since 2004. Only increase by 100 in the IgG, only .1 increase in m-spike, no change in total protein, glucose down so much wondering about that drop, only 89. I was already clapping my hands and cheering and about do a happy dance with the nurse, (doc didn’t even come in, she ran back and forth to ask him questions). But her response to my celebration was that “these things tend to go south very quickly”. I just had a dexa scan and brought in the tests as normal and she seemed more displeased that my endocrinologist had ordered it, than pleased that the test was normal, not even the borderline osteo of a few years back anymore. She asked me if I knew about Thalidomide that I might soon be taking. When I involuntarily rolled my eyes, and shook my head as if trying to shake her off, she stopped talking about it. She gave me an order for the skeletal survey, said the dexa wasn’t good enough; and the last straw as I walked out the door she had entered into the computer, MM on the order. That hasn’t shown on any previous orders. Thanks to you and others, I have enough knowledge to disregard what is not up to date treatment. I’ve been taking 6 g. curcumin, a feverfew tablet(called mygrafew, I put dehydrated powdered feverfew on my turkey sandwich, from the plant out back, milk thistle, boulardii probiotic, krill oil, calcium. My hemoglobin was lower but still normal (need more meat?). For the first time in ten years I don’t have ear aches, thanks to a new ENT who gave me a ear wash I use twice a day instead of the constant onslaught of antibiotics. I came home from my onc appt. and did a happy dance with my cat instead. I’ve gotta go looking for another onc, losing count. Wish there was a way to interview them before going through all the paperwork.

  3. “Indeed, early intervention may only serve to identify those patients at early risk for progression, or worse, theoretically to select out more aggressive genetic subclones of myeloma.”

    Margaret –this is a very interesting blog with lots of good points but I was struck as you were by the above sentence.

    You suggested it might mean “that early intervention might turn a not-so-aggressive type of myeloma into an aggressive type.” By what mechanisms could this happen? How would treatment modify the aggressiveness of myeloma? I can see many negative effects from the chemo of course mainly from side-effects but how does it change the basic nature of the beast?

    I wonder if they are also saying that by treating these patients you find out which people respond and which do not thereby exposing the more resistant ones. However I am not suggesting early treatment as I for one have smouldering MM and do not want any treatment until I absolutely have to.

    You also make a very good point about the numbers of patients in a particular cohort and too often “important” points are made with too few numbers. The proper use of medical statistics is supposed to make things more valid but nevertheless this keep happening time after time.

    1. With the devastating problems that chemo causes, including Destroying your immune system. This is the major thing one has going for them when trying to eliminate any disease. When people say they are battling cancer, they don’t seem to understand that as soon as you undergo chemo, the battle is lost. It’s amazing that with computers everywhere, people don’t seem to do any research. What percentage of patients with nearly any type of cancer are alive in five years. I have had full blown MM for nine years with good success . Early on , I tried Velcade and Dexamethasone and within a couple of infusions, I weighed 16 pounds more than before I started. I was nearly in respiratory arrest and in A-Fib I was in the hospital for a week on IV Lasix. Thankfully, my heart went back into sinus rhythm. My primary meds are high dose Vitamin C, B complex and DMSO. Unfortunately, it has stopped working and I tried a course of cannabis which is often very successful, but not for me. I am now having kidney problems, so it seems I’m about ready to call it a day. I’ll be going back to my doctor to see what he recommends. BTW– I didn’t mention that I am 85 years old.

  4. Thanks Beth
    That’s my plan, not so intimidating to do at this point. This one was a new one. I just reread all I wrote, sorry for so much run on, had a lot of anxiety mixed with relief in me. I’ll be getting the bone survey as was ordered.

  5. Hi Margaret,
    I am a SMM since year 2004 and with normal IGG since than until today. I have done the Thailidomine and Dexa and radiotheraphy in Year 2003 and have no others treatment for 5 years.
    Hope to have more 5 years to come.
    Chee Wai

  6. Linda: much better to dance with a smart cat than with a bitter ignorant nurse…! Your story reminds me of when my hematologist asked me: “why don’t I give you some thalidomide to bring down the number of MM cells in your BM?” I replied so quickly and forcefully (“No!!!”) that she was quite taken aback. I doubt that any of her patients ever say no to her. This probably happened in early 2007, so I hadn’t been her patient for very long. Well, that was then…now she believes in what I am doing (or at least she says she does…!). But it took some time…and quite a number of test results! Good luck on your search for a new onc! BTW: “Myeloma” is the diagnosis on all my official medical papers, too. No worries!

    Gerry, a couple of MM friends told me that they were essentially pushed into early treatment at a time when they had no CRAB symptoms, their myeloma was slow-growing, etc. But once they began treatment, boom!, the myeloma took off…became aggressive. They both regret having taken that path. I can’t say more than that for privacy reasons.

    Chee Wai: here’s to another 5, then 10, etc.!, years!

  7. Chee Wai:
    I’m glad to hear you’re doing well. I am wondering since you had SMM presumably with no CRAB involvement why did you choose to undergo treatment? Did you feel pressured by your physician or did you have other reasons?
    I am very interested to know how people make their decisions regarding SMM and MM. I suspect one day I too will have to make that decision.

  8. Hi Gerry
    I have no idea what was SMM back to the 5 years ago. So,I just followed the doctor recommendation.
    Anyway, since then I took Curcumin and Barley Green everyday with less meat intake.


  9. @Linda,

    I know since one years that i have MM. I was afraid of this disease and the doctor. The doctor was perhaps a good doctor, but not communicating with me. Now I have another doctor and that was a relief: she told me many things and only then I could tell what I wanted and how I was thinking….

    Indeed, a kind of intake interview seems a good idea ….


  10. “Indeed, early intervention may only serve to identify those patients at early risk for progression, or worse, theoretically to select out more aggressive genetic subclones of myeloma.”

    I read this as implying that if you have a “more aggressive genetic subclones of myeloma” present then that subclone will be the least altered or suppressed by treatment. It might be all that is left behind after treatment… the only MM that is around to progress.

    This would be similar to the process by which the most antibiotic resistant strains of a bacteria are the only strains left alive after a course of antibiotics. This could lead to a highly antibiotic resistant “super bug.” Early SMM treatment could lead to killing of all but a treatment resistant subclone of MM.

    The key words are “select out”. Implying that if you don’t have a highly aggressive subclone to “select out” then early treatment would not create one.

    This of course is all conjecture on the part of the authors (and me for that matter).

  11. “The key words are “select out”. Implying that if you don’t have a highly aggressive subclone to “select out” then early treatment would not create one.”

    Hi LP Cells — Of course we don’t know the exact truth but I think you have explained this very well. And maybe it gets back again to the question of cancer stem cells as the most resistant to therapy. Finding better ways to destroy those is no doubt a big challenge in research today.

    Also as gene expression profiling of cancer cells progresses one will be able to pinpoint more accurately which cells –and tumors– are more aggressive and more resistant to therapy.

    I sure hope that therapy can become much more specific for cancer cells rather than blasting everything with all the “collateral damage” to normal cells and tissues.

  12. Hi Margaret,

    Your blog has been so helpful to me and my family. I totally agree with u when you say; what about the younger patient. I am only 47 and recently diagnosed with mgus high protein spikes. My life is at a complete STOP… Prayers to all and hopefully more research being done for this MGUS pre-cancer early stage disease.

  13. After the destruction of the Temple
    prophecy was given only to the fools.
    So I will be very careful and say
    that when we have a good medical insurance
    we tend to see using it to the maximum as a privilage.
    to remind us a single pt/ct is like getting plain chest radiography every week for a year (radiationwise)
    that alone if done too frequent may in 15 years cause MM to a totaly healthy person.
    Also as we look back how little we knew about MM in the past
    I did a seminary work on the subject (as a nurse) in the year 1990 and I do’nt remember hearing about SMM
    in those days.
    So how can we foresee what we will know in the
    year 2027 (not even the late Harry Potter could).

  14. Does anyone have any info on the import of foot problems with SMM–? I have had bunions for a long time– but now my left heel and both balls of feet are quite painful mainly in the morning– thanks for any input !

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