Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. Part I.

I have to split this post into two parts, since it’s soooo long (I will publish part II tomorrow). It concerns a study on smoldering (asymptomatic) multiple myeloma published last month in the “Journal of Clinical Oncology”…Sherlock, grazie!, sent me the full text…

In the abstract (see:, there is a list of some of the risk factors for progression to full-blown myeloma, nothing new, here—M-protein size, percentage of bone marrow neoplastic cells, etc.

Interesting excerpt: Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome = this bit is explained more in detail in the full study, so we will get to it later. The following excerpt simply confirms what we already know: Patients should not be treated until progressive disease with end-organ damage occurs. There are so many things to keep in mind with myeloma…but this one is certainly NUMERO UNO: no CRAB, no treatment.

Now for the full study. Something I didn’t know (or didn’t remember…) is that smoldering myeloma was first described in 1980 by Drs. Kyle and Greipp, as follows: a distinct clinical entity characterized by the presence of a serum M-protein value higher than 3 g/dL, bone marrow clonal plasma cells (BMPC) involvement of 10% or higher, and no bone lytic lesions or clinical manifestations attributable to the monoclonal plasma-cell proliferative disorder. A distinct…er… “entity”? I’m walking around with an entity inside of me??? Hehe, that gave me a bit of a chuckle…

Problem: the diagnostic criteria have not been uniform, thus resulting in important differences in time to progression and in a lack of consistent predictors of outcome between the different series. (The “different series” bit refers to the different classifications of asymptomatic myeloma: SMM, indolent myeloma, asymptomatic myeloma or low tumor mass myeloma.)

Before 2003, there was no real consensus on how to define smoldering myeloma, or SMM. In 2003, the International Myeloma Working Group agreed on a new definition of SMM consisting of a serum M-protein of > 3 g/dL and/or > 10% bone marrow plasma cells with no evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia or bone lesions [CRAB]).

The study then spells out the differences between MGUS and SMM, but I won’t focus on that, since we know them, or should know them! ;-), by now. The following, however, was new to me: When the M-protein size and the proportion of bone marrow plasma cells are consistent with MGUS but there is substantial albuminuria, congestive heart failure, renal failure, peripheral neuropathy, orthostatic hypotension, carpal tunnel syndrome, massive hepatomegaly, malabsorption syndrome, or any combination of the above, the most likely diagnosis is primary systemic amyloidosis (AL) […]. Something to keep in mind…

…as well as a few other things: elderly folks can have diseases that mimic myeloma, for instance an increase in serum creatinine, anemia, diffuse osteoporosis and so on. Even patients with a single asymptomatic lytic bone lesion, the possibility of an associated benign bone cyst or a bone angioma should be considered […]. So ONE bone lesion doesn’t necessarily mean that you have developed active myeloma…interesting…my notes are filling up my…mental pad!

Risk factors for progression: M protein > 30 g/L, bone marrow plasma cells > 20%, haemoglobin > 12 g/L, light chain proteinuria (Bence Jones) > 50 mg/24 hours and an IgA monoclonal heavy chain. And lytic bone lesions. And, going down the list, also the presence of MRI abnormalities. A personal note: at times, my M protein has gone above 30 g/L, in fact in May 2009 it went as high as 39.9 g/L (eek!)…then it went back down to 29.7 g/L in September 2009…so I am still smoldering…what I mean to say is: please don’t freak out if your M protein surpasses the 30 g/L limit…first look at the context and the trends…

An interesting paragraph is titled “Pattern of evolution.” According to a group of researchers, there are two kinds of SMM: 1 evolving and 2 non-evolving. Patients who fall into group 1 had an increase in M-protein levels in two follow-up consecutive visits. Group 2 was instead stable and had a longer time to progression (3.9 years versus 1.3 years).

And here we get to a very useful item that was mentioned in the abstract, too: Most patients with SMM progress with increasing anemia and/or skeletal involvement consisting of bone lytic lesions and/or diffuse osteoporosis. Anemia is defined as having a haemoglobin lower than 10g/dL…but hey, read this and breathe a sigh of relief: the authors of this review have seen patients with SMM with a Hb level between 9 and 10 g/dL with no need for cytotoxic therapy for several years. It must be considered that in patients with a high serum M-protein there is also a component of hemodilution, and so the severity of anemia may be overestimated.

Wow, now this bit of news is very very important…it proves that treatment protocols should not be applied too rigidly, as happens all too often!!!, but that each case should be evaluated carefully…in its own context. In other words, just because your Hb has dipped below 10 g/dL doesn’t necessarily mean that you should undergo immediate treatment…that number could in fact remain stable or even go up…So this is another thing for us to keep in mind…


  1. Ciao Margaret,
    I have smoldering myeloma since 10 years including skeletal involvement consisting of bone lytic lesions. Treatment protocols are not be applied also in my case with lytic lesions since 2002.

  2. Margaret:

    I’m newly diagnosed with SMM. First blood test for M-spike was in October ’09 and final diagnosis was last January. I’ve found a lot of info on MM and even went to a MMRF seminar a couple of weeks ago. They always reference SMM but then just go on to full blown MM. I’m on top of my M-spike number 1.9 and my marrow plasm cell load of over 10% but that’s about all. Do you have some additional information that I can read to help me with all this? ie.. you references an m-protein of >30 g/L.. What does that mean? How is that different than an m-spike of 3.0? I go for a follow up blood test April 1st and they are sending the results to me to follow. What should I be looking for other than my M-spike? Thank you for your great blog and thanks to Pat for the link.

  3. Margaret,

    As you know I am right in the thick of SMM and reading lots of articles and blogs especially yours. SMM like MM is definitely a heterogeneous disease with lots of different types of presentations. The numbers may get confusing at times but I totally agree with your mantra: NO CRAB, NO TREATMENT!


  4. Hello Margaret and others. I feel so fortunate to have found you.
    I was diagnosed with MM on 23rd December 2009. What a Christmas! Have been going to Haematology every two months for blood checks. Last there 24th Feb. Still called Asymptomatic. I can’t believe how much you all know about the condition as I’m still researching.
    I’m currently reading a book called “Living Proof” by a man called Michael Gearin-Tosh who actually had MM around sixteen years ago and as far as I gather from what I’ve read so far is not going for the conventional treatment.

  5. Margaret,

    I too am so thankful for the information I’ve been able to read from you. I was diagnosed with SM in March and reading those blood test numbers is so confusing. In 3 blood tests Ive taken, my protein numbers have gone from the 600 range to the 900 range to my most recent 1500 range. Not sure what it all means, but I have absolutely no signs of anything negative going on in my body.

    I have changed my diet from seeing a nutritionist, but can you share your basic diet including supplements and philosopy. Currently, she has me off all sugar, even fruits. She has me off wheat and drinking a gallon of water daily with lemon and peroxide. Your thoughts would be appreciated.

    Thx, Joe

  6. In July 2009 I was diagnosed with early multiple myeloma. I had a bone marrow test done. I have no symptoms and I’d like to know, for how many years it can stay asymptomatic and also for how many years could it have been lying dormant prior to diagnosis

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