New study: prognostic factors associated with progression of smoldering multiple myeloma…

A blog reader, thanks!, gave me the link to this recent smoldering myeloma study, an Italian study published in July in “Cancer.” You can read the abstract here:

If you skip down to the Conclusions, it’s clear what this is all about: smoldering patients with at least 60% plasma cells seems to be at a higher risk of progressing to active myeloma. The authors recommend that these folks be “treated soon after diagnosis.” By the way, at the end of the Discussion part of the full study, this “soon” changes to “right away.” Now, in my book, “right away” is not the same as “soon,” but…perhaps I shouldn’t be so bloody picky…hmmm. 

Anyway, other “progression” parameters that you can find in the abstract: hemoglobin equal to or less than 12-5 g/dL and monoclonal component equal to or more than 2.5 g/dL. 

Okay, let’s have a look at the full study, without going overboard.

In the first paragraph, the study reiterates what we smolderers already know or should know: that, statistically, the risk of progression is 10% in the first five years. Incidentally, I can’t help mentioning that I’m at year 7 now…7 years and going strong!!! 🙂

And then they ask the key question: how can you figure out which SMM folks are at higher risk of progression? And WHO will progress more quickly?

To this I would add my own questions: if it were possible to know the answers to those questions, would you really want to know? Would it change anything you’re doing?

As far as I’m concerned, I can answer that I wouldn’t want to know, since I know that stress is such a significant factor in myeloma progression. In fact, it seems to be of particular importance in the early stages of myeloma. [In 2007 I wrote about an important Ohio University study the effect of stress on myeloma…Have a look at my Page on “Myeloma and stress” (scroll down my Pages on the right…it’s in the Myeloma section).]    

At any rate, thus far, the Italian authors claim, it has been IMPOSSIBLE to determine who will progress and who won’t, or who will progress rapidly and who will progress slowly. Lots of different, complicated (expensive) systems have been suggested, they say, but…well, these systems simply DO NOT work, including the complicated one set up by a group of Spanish researchers (= yes, I’m referring to that awful Spanish SMM-chemo trial designed by a bunch of researchers, including many who are CLOSELY tied to Celgene, hellooooo??? This trial stinks 100 times more than a fish left in the pantry for a month…). Where was I? Ah yes, fact is, all the “progression” systems created thus far DO NOT WORK, according to the Italians.

Well. Well. Well! Interesting.

And this leads to an excellent point, a point with which I happen to agree wholeheartedly!, that treatment in the absence of any symptoms has NO BENEFIT in terms of overall survival. Hah.

I’ve been saying the same thing for years…


The standard for SMM care, the Italians say, IN THE ABSENCE OF RELIABLE ELEMENTS TO PREDICT DISEASE PROGRESSION, is close follow-up without treatment.

Precisely. Esattamente

The authors then mention a Mayo Clinic study published in August 2011 in the New England Journal of Medicine (see, which states that In patients without end-organ damage at diagnosis but with 60% or greater bone marrow involvement, the clinical course is characterized by progression to symptomatic myeloma within 2 years. Such patients should be considered to have myeloma that requires therapy at the time of diagnosis.

Statistics at work…again. Remember the Stephen Jay Gould essay on statistics? If not, please go read it. It’s excellent. I have a direct link to it here on the blog (scroll down and look on the right; it’s under “Useful links,” almost at the end…) or you can look it up via its title: The Median isn’t the Message.

Well, my own bone marrow “involvement” was “only” 50% in 2005 (that’s what changed my diagnosis from MGUS to SMM, in fact), which is obviously lower than 60%. But I have a real-life smoldering friend whose bone marrow biopsy result was 70% in November, 2005. So she would fit right in with the progression-within-two-years group.

But here’s the thing: she has NOT progressed and has no CRAB symptoms. And she’s doing fine. Perfectly fine. 

So much for progression in TWO years…So much for statistics. 

Anyway, back to the Italian study. According to these authors, progression risk was based on the following: hemoglobin or HgB, m-spike (monoclonal component), bone marrow plasma cell involvement rate; Beta-2 microglobulin, ESR (erythrocyte sedimentation rate; = VES in Italian), serum calcium, gender and age.

Of these, the really important ones were HgB, m-spike and bone marrow plasma cell rate, especially if it was above, or equal to, 60%.

As I mentioned at the beginning of this post, the authors believe that the subset of patients with a 60% or higher BMB result should be treated “right away”…that is, before any CRAB symptoms appear.

OUT-RAGE-OUS. This is a perfect example of a sweeping, generic statement bordering on the ridiculous, if not the dangerous: “oh yes, uhm, let’s just give chemotherapy to any smolderer whose BMPC involvement is at least 60%…”


Interesting bit of news: according to these authors, the best way to identify the subset of what they have identified as “quick-progression” SMM patients would be to do a bone marrow ASPIRATE, not a bone marrow BIOPSY. You can find two references to this in the abstract…e.g., where it says: BMB was more sensitive for the detection of BMPC involvement, even though BMA was a more reliable indicator of a rapid progression to sy-MM.

Well, at the end of the full study the authors go as far as to state that this BMA finding strongly suggests that BMBs is NOT helpful to assess SMM patients…

Holy cats, mackerels, kingfishers and puffins! 


  1. Smouldering 7 years!!! Good girl!! 🙂

    I don’t want to jinx myself but I’m happy to report that I have been smouldering for 6 years!! 🙂

    One question…since BMBs are not helpful in assessing SMM patients…does that mean we can say “No thanks Mr. Dr.” when they come at us with that drilling tool they use? 🙂

  2. Margaret: Congratulations on 7 yrs smoldering!!
    What a great article you have brought forth. Yes, you are definitely incredible in bringing us this fund of knowlege. Bravo (I had happy that you posted as I had not read anything from you in sometime; attributed to school and taking care of cats & hubby.

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