Does MGUS always precede myeloma?

A while ago, I asked my dear Sherlock (grazie!) to send me the study on this very topic, published in the January 29 2009 and also the May 28 issues of “Blood”: (Update: after writing and publishing this post, I discovered that the full study is available for free online, just click on the tinyurl link, then on “full text”; please note that there is also a related Spanish article titled “Are all myelomas preceded by MGUS?”…you will find the link almost at the bottom of the page).


12 researchers from different cancer institutions examined the cases of 77,469 individuals who had participated in the nationwide population-based prospective 1992-2001 “Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial” or PLCO. They identified 71 patients who developed MM during the course of the study. A series of tests determined that almost all had passed through a prolonged pre-malignant stage (8+ years before diagnosis). I would like to point out that, at the beginning of the study, all the trial participants were healthy.


A few details concerning the 71 myeloma patients: 71.4 % were males, and the average age was 70. Important note: 8+ years before their MM diagnosis, 82.4% of these patients had MGUS. But 2 years before their MM diagnosis, 100% of them had MGUS. Therefore, In the present study, an asymptomatic MGUS stage preceded the diagnosis of MM in all cases. “In all cases.” Wow. Anyway, you can read a few more details and numbers in the abstract.


The full study begins with the usual dire statistics…skip skip skip. Then we find the crucial question: is myeloma always preceded by asymptomatic MGUS or SMM? If so, the researchers say, then we need to focus on identifying risk factors for MGUS and to improve our knowledge on underlying mechanisms of transformation from MGUS to MM, with the aim to define better predictive markers of progression and to develop chemopreventive approaches. Good idea!


And then: how can a preceding MGUS stage be ascertained in folks who are diagnosed with myeloma? If there are no blood samples from previous years, that would be impossible. And in fact the researchers write that Thus far, it has been impossible to determine if a protracted premalignant phase (MGUS) precedes MM in all patients.


“Thus far.” But the above-mentioned Screening Trial gave these researchers the golden opportunity to test blood samples taken from patients 8 years plus before their myeloma diagnosis. All that blood was tested via serum protein electrophoresis, immunofixation and FLC assays.


Interesting titbit. MGUS and SMM were lumped together, because for the purposes of this study our interest was to determine whether a premalignant asymptomatic stage preceded all cases of MM, regardless of whether that stage met the clinical diagnosis of MGUS or smoldering MM. So when we read MGUS in this study, it also means SMM (my current stage). Good to know.


A few more details: the researchers discovered that about 50% of the MM cases remained fairly stable…whereas the rest had a yearly M-protein increase. In the end, though, all of these patients—the fairly stable ones and the, er, more unstable ones—progressed to active myeloma (well duh, this is hardly surprising, since the researchers examined patients who ended up being diagnosed with myeloma…not those who remained MGUS or SMM).


In the Discussion, the researchers write that virtually all MM cases are preceded by MGUS. They then add: At the same time, however, one has to keep in mind that the vast majority of MGUS cases will never develop MM. It depends, they say, on the status of risk factors such as a high serum M-protein level, non-IgG MGUS and so on. In the absence of risk factors, the likelihood of progressing to active myeloma is itsy bitsy teeny tiny.


The researchers point out that it would be important to identify, via molecular markers and whatnot, the subsets of MGUS cases at high versus low risk of developing MM. Our finding that MM is universally preceded by a prolonged premalignant stage with up to 75% of MM patients having detectable M-protein 8 or more years prior to diagnosis of the malignancy fills a key gap in the present literature on myeloma-genesis.


They then add that even those who have had MGUS (or SMM) for 25-30 years may progress eventually to active disease. So our risk of developing myeloma diminishes with every “stable” year that passes but never vanishes, so we have to resign ourselves to be monitored for the rest of our lives. Well, no surprises there…


I came across an interesting hypothesis concerning those who progress from MGUS to active myeloma. In these particular cases, the researchers suggest that MGUS might not be a benign condition at all, but rather a slow-growing form of myeloma. They write that Although it remains to be confirmed, we have speculated that “evolving MGUS” potentially could be a reflection of an “early” myeloma with a slow rate of progression. Well, well…


There were a few drawbacks in this study, such as the lack of a younger-than-55 population: the population-based PLCO cancer screening study enrolled healthy individuals who were 55-74 years at baseline […]. And let’s not forget that the average age of the 71 myeloma patients was 70. Quite a big drawback, especially for younger folks like yours truly. Oh well. 

The study ends with the following statement: Thus, regardless of the terminology used (MGUS or otherwise), we can confidently say that the presence of an M-protein in 93% of patients with MM seven years prior to diagnosis of MM as seen in this study strongly confirms that a protracted premalignant stage (biologic MGUS) precedes all cases of MM. […] Future studies are needed to provide new insights on the pathogenesis of MGUS and better predictors for development of MM in order to take early actions to prevent or delay MGUS progression.

I would have been curious to know how many of the PLCO participants remained MGUS or SMM. Too bad that data couldn’t have been included here. Oh well…can’t have everything!


  1. hello Margaret – I read with interest (and dread) this post about MGUS to MM and the almost impossible way to avoid progressing given enough years!!! As an MGUS I avoid thinking about that possibility, a form of denial, but I remember that many research papers indicate that nutrition has a great role in many cancers – breast, colon, prostate among others. Using that as my guide, I use nutrition as preventive chemo – a term used by Dr. Béliveau, a doctor in Montreal who has written a book about the power of healthy diets to prevent many cancers. So I eat my 2 to 3 pounds of brocoli a week, and cauliflower and red sweet peppers, and sweet potatoe and berries, hoping and praying that it’s anti-cancer. And yes, sometimes, after my 10th meal containing brocoli in one week, I say: It better be good for me!!!

  2. Hi Marguerite, after reading your comment, I decided that I should highlight an important point made in the study (and in many other studies as well): “the vast majority of MGUS cases will never develop MM.” Never!

    The Mayo study isn’t as dismal as it may seem at first glance. The researchers examined ONLY the people who were DIAGNOSED with active myeloma, not those who had MGUS or SMM, as I pointed out in my final paragraph. So we have no idea how many MGUS and SMM cases there were…perhaps many!

    I strongly believe that we would make a terrible mistake by going through life dreading the possibility, NOT the probability!, that we might progress to active disease one day. That may or may not happen. And, as you point out, there is preventive “chemo.”

    Speaking of which, I have to say that I commend you for the amazing amount of broccoli that you eat. Wow. As for Dr. Béliveau, I have read some of his books, too. His anticancer recipe book, in fact, is in my kitchen…

    Anyway, I will simply not allow any feelings of “dread.” Especially not at your stage!

    As we say in Italian, “non ti preoccupare”! 🙂

    1. Keep in mind that broccoli SPROUTS contain much more of the anti-cancer chemicals than the broccoli. It’s easy to grow the sprouts at home.

  3. Your interpretation of the clinical findings is fascinating, Margaret, and hopefully useful for those physicians who find MGUS in patients to give them special monitoring and to even think about MM as a possibility. Too often I have read of diagnoses which were masked by other ‘ailments’ upon which the doctor focused, letting precious time go by without treatment for the MM-diagnosed – finally! As the relative of someone with MM, I have read (and contributed to) a variety of blogs, but the one consistency I see is that MM is ‘tailor-made’ to the individual, and really must be attended to just as a tailor fits a suit… allowing for the differences in each situation. But if it is true that some commonalities exist prior to diagnosis, (just as there are many suits off the rack which need to be fitted) perhaps there is hope that these clues of commonality can lead to better ‘fittings’ or treatments overall.
    Thanks for your work on this subject.

  4. Hi Margaret,
    I’ve decided not to worry about it either. I’d rather play Scrabble with you and Winna! I luv Scrabble and my family won’t play with me…they think it’s boring! (Does anyone have any cheese to go with this whine?! : ) Thanks for the good work that you do!

  5. Once again Margaret Comes through with info!!! My Hero. I’d be interested to know how many had neuropathy and othe symptoms they say are not atributable to MGUS. Seemsto me by using folks with MM they are working backward to prove their hypothesis- interested to know who funded this- maybe pharma with some Mgus meds?

  6. Just found your blog while going through what my search engine pulled up about MGUS. My neurologist just told me that I have last Friday. Most of the sites say either that it is a precancer situation or that is a benign state with no symptoms. So confused. So I am very happy to find you.

    My neurologist says that I only have Carpal Tunnel so we are still searching for why I have tingling or itching or electrial like shock sensations all day and all night all over my body. So, this came up while searching.

    Keep up the good work!

  7. Carol, Dr’s continue to insist there are no problems with MGUS however Myeloma Assn. has a page on neuropathy for MGUS. is a good resource too – we mostly deal with this with alternative treatments that work for myeloma sufferers. More younger people seem to be diagnosed with MGUS than posted statistics. My DR finally diagnosed me with fibromyalgia because the neuropathy was debilitating and I am applying for disability, I need a diagnosis the SSD board would recognize. It’s frustrating, it can turn to myeloma but not necessarily ….I’ve been dealing with this since 2006 … if it is going to go to myeloma it won’t be quick and I use circumin, vitamins and diet to slow the progression. For me the shocks stopped and slowed leaving neuropathy behind. It’s as if you have MS and your nerves are demylenating after the tingling is numbness. Not fun but livable…my thoughts are to change what you were doing when you got this, your environment contributed, Good luck, I believe stress is a big culprit.

  8. Hi Paul,
    I had them checked and they are fine now. I am taking a prescription grade supplement (Mag-X). Originally, I had leg and toe cramps every single evening and my doctor put me on quinine. Then they stopped making it and my pharmatecist reccommended it instead. It worked and I no longer have the evening cramps. Thank you for thinking of it.


  9. Gee, Paul, I didn’t know that but I am new to MGUS and all. At least I have been taking extra magnesium for years.

    Thank you,

  10. Hi Carol,
    It is very frightening when you first hear the words MGUS & myeloma. The important thing to remember is that many people have had stable paraprotein levels over a long period of time – some more than 20 years without any conventional treatment. Touch wood, I have been stable since 2005. I have found omega 3 (flax oil), green tea, vit D, curcumin, DHEA, and black seed oil helpful in reducing the symptoms I’ve experienced. I have also been on a gluten free diet for 2 years and have just started taking Magnesium.
    You might find it is useful to think about what your body is telling you is going wrong and hopefully, with some research, you will find what you need to prevent the condition progressing.
    Best wishes,

  11. When I was told, MGUS was entirely new to me, then my neurologist mentioned Multiple Myeloma and that treatment for it is a horrible experience and not promising. Will need to see what supplements I can afford financially to add. Will need to research to find out the benefits of the ones that you are taking. Thank you for your list, that helps. Will concentrate on those that help my nervous system as that is the worst right now. I appreciate your help.


  12. Just diagnosed w/ MGUS this week and don’t know what to do regarding the stinging pain that hits me in different places all over my body. It started out in my left big toe then under the arch of my left foot, slowly progress up my leg to my fingers, top of my hand to my arm before moving to the right side of my body. All over now, even my inner thighs. I have good days and bad days…but would really like suggestions of what to take that would help. I’m on 2 Cymbalta (30 mg) daily, now. Not really sure it’s helping…been on it for 2 months, now. Was on only 30 mg a day until 1 week ago when the pain worstened. Oh well, I know the Lord will give me the grace that I need to deal with whatever. Now, it’s not so bad because I work from home and have a VERY understanding boss. Lots of doctor app’ts to find out what I actually have. I’m thankful it’s only MGUS and they said only about 50% will develop multiple myeloma. PRAISE THE LORD I can even feel anything…some people cannot feel anything below their neck. We should be thankful, huh? 🙂

  13. Hi Diane,
    You nay want to see if yiu can get a higher dosage of Cymbalta. I was taking 60 mg, at night but but neurologist changed it to twice a day and it really helping. I am having the same symptoms as before but they have been toned down quite a bit.

  14. Diane, in addition to talking with your specialist about this pain, why don’t you join the MM Support (MMA) patient listserv (see on the right-hand side of this link: and ask if anyone else has experienced the same symptoms. I am sure that you will find some good advice there.
    Another point: that 50% sounds super wrong to me, I don’t have the time to check on that now, but if you don’t have any of the progression risk factors, the number can’t be more than 5% a year.

  15. Hi, I’m a 43 yr old female that just had a routine blood test done. My doc said “theres one level thats a little high, but don’t worry, I’m sure it’s a lab mistake”. I said, “What if it isn’t? What would that mean?”. He said, “Believe me, you don’t want to know.” So I repeated the test just to be sure and got the call that shocked me, I needed to see an oncologist. He in turn sent me for a bone scan a few days back. The oncologist said he didn’t think I had cancer thank God, but I need to see him in six months if this scan turns out ok. So I have Mgus. Information on the internet is confusing, I see 50 percent go on to MM, another site said 20% and now may never get MM great, wish I knew what to believe because the stress and worry now overwhelm me at times without even being diagnosed. The waiting to hear what’s going on is tough. I’m not in my 70’s and I’m not a man. I guess that’s rare. Or is it? If there’s a study going on I would be willing to participate.

  16. Hi Kim,
    The important thing to remember is that 1-3% of people over 50 are supposed to have MGUS and Myeloma is relatively rare. Your doctor has probably found a paraprotein in your blood and there could be a number of reasons for it.
    If you can, try to get a copy of all your blood test results and have them interpreted by someone who knows what they are talking about. Not all GPs understand the significance of paraproteins.
    The important things to look out for are the level and type of paraprotein and how fast it is increasing.
    If you have had a bone scan and that is clear and your oncologist doesn’t want to see you for 6 months, I wouldn’t worry. Many people have stable paraproteins for years and do not require and treatment.
    Also, if you read Margaret’s wonderful blog, you will find that there is a wealth of advice on supplements (curcumin, green tea, omega 3, etc) which can help your condition and keep you in good shape.
    Best wishes,

  17. Have been diagnosed with MGUS for 3 or 4 years. I was frieked out at first too, this is no dress rehersal. But if you change some things, reduce red meat, more veggies, supplements and laughing more often, refusing to participate in stress, what have you lost. But if you continue eating poorly, sitting in the midst of chaos and stress and it develops into MM—well the definition of insanity is doing the same thing and expecting different results. I haven’t had insurance for over a year and I have no idea what my m-spike is doing but even though I have a lot of neuropathy, I have laughed more and not worried so much this last year, there’s some things good to say about ignorance. So get out there and live!!!

  18. I found this on the website of

    “Treatment for monoclonal gammopathy is not required, although research protocols are in existence for patients at centers that specialize in the treatment of monoclonal gammopathy and multiple myeloma. The reason why these proteins are a concern is that patients who have them have a higher risk of developing a more serious blood or bone marrow problem such as multiple myeloma. Fully 80% of patients with a protein abnormality will never develop any problems related to it. However, because 20% of patients might go on to develop problems, careful follow-up is required. This may only require an annual blood test. This blood test, protein electrophoresis, can be done in virtually any hospital laboratory. For most individuals, a bone marrow examination is not required. More in-depth testing may be done if the protein level has changed or if symptoms develop.”

  19. I’ve had M.G.U.S. for about 8 years. The diagnosis was overwhelming as I was just having test for my sore back. My orthopedic surgeon said he routinely test blood because back pain is a symptom of M.M. Anyway for the first 2 years I was tested every 6 months. After that I said forget it, I can’t take the stress of testing and waiting to see if this time is when the axe falls. I’d rather not know when it gets me. I had a close friend die from M.M. and it was nasty. She postponed death maybe 6 months but it was six months of hell, ports for treatments in her chest, chemo, stem cell transplants, radiation then death. Not pretty, and I don’t want any heroic efforts to give me 6 months. Ignorance is bliss.

  20. Hi All,

    I just found out that I have MGUS, and M spiked IG Lambda. My Doctor stated that I had this plasma cell disorder for 10 years, but recently informed me about this disease. I was very upset that the doctor would not tell me or give me the proper information that I needed; then I had to tell the doctor basically what to do.

    Several doctors at the VA are not prepared to handle many veterans that have this condition and many of us were succumbed to water that was tapped with JP5 fuel(Benzene agent) in out drinking water, while we were all on the Ship. I got severly ill and was taken off the ship but my symptons continued to this day.

    Other predisposing factors, I was involved in doing asbestos jobs without no proper equipment and involved in the water contamination situated that occurred at Camp Lejeunce, NC that had severely cancer-causing agents. Sadly, I can definitely relate to the itching, tingling, neuropathy and on-going Bone pains, especially in the back, ribs and ankle areas.

    I had to do my own homework on this disease because some doctors just don’t know and just like I had to take charge of my condition and that’s when things started to get done for me. I pray that each of you stay on top of your condition and not to be frightened, because God and faith will conquer all.


  21. Frank

    I am sorry for the quality of care you have received,for someone that has served our country. Our healthcare delivery system is very fragmented often with several doctors treating a patient with very little communication taking place. This is why we must be advocates for our own health. IMO you should always ask for copies of any laboratory , or other test results. You have the right to obtain these. Thanks again for your sacrifices and god bless.


  22. I have MGUS age 67 had a knee replacement Dec-2014 right knee, have booked for my left knee in Nov-2015,my rt knee feels good however I have arthritis, the rest of my body hurts mainly my back legs hands & shoulders no energy does anyone out there that has MGUS have similar pain “issues” Thanks Marv

Leave a Reply

Your email address will not be published. Required fields are marked *