A high-risk SMM study presented at ASH 2009

Today a blog reader’s comment prompted me to finish editing this post, which I actually wrote a few weeks ago and then left buried in my ever-increasing pile of drafts, sigh.

Last month, a study, presented at the 2009 American Society of Hematology meeting (see: http://tinyurl.com/yz965fc), was brought to my attention…a study concerning high-risk smoldering patients, i.e., patients who are NOT in the stable “watch and wait” category. This is an important distinction since, according to a 2007 Mayo Clinic NEJM-published study (see my January 11 post: this is an interesting study that, however, examines a relatively small SMM population, so it should be taken with a rather large side dish of caution…), only a small percentage of SMM patients progress to active myeloma every year.

The 2009 ASH study authors declare right at the beginning that Several small studies have explored the value of early treatment with either conventional agents (melphalan/prednisone) or novel drugs (thalidomide, interleukin-1b), with no clear benefit. It should be noted that these trials didn’t focus on high-risk sMM.

Notice these words: No Clear Benefit.

And now let’s see how the authors define a “high-risk” smoldering population:

Criterion A: at least 10% plasma cells in the bone marrow.

Criterion B: an M-component of at least 3 g/dL.

If only one criterion is present, then, according to these authors, a patient must have other “aberrant factors” in order to be classified as “high risk” (see above-mentioned abstract for details). Well, that would have excluded me from participating in this study. Even though I probably still have a decent amount of myeloma cells in my bone marrow, my M-spike has never gone as high as 3 grams/dL, and all my, er, factors are far from…aberrant.

Not that I would ever have accepted to be part of this study, and I will give you a few good reasons why:

  1. The study lasted from October 2006 to June 2008…not long enough to reach any conclusions, in my opinion, especially given what follows…
  2. Some of the 40 “high risk” smolderers who were given lenalidomide (=Revlimid) and dexamethasone suffered from severe side effects, as we will see in a second…
  3. Complete remission or CR was achieved by only 11% of the 40 patients mentioned in the abstract (there was also a 5% of stringent CRs, see http://tinyurl.com/y8ty9vr for more details on this type of remission). Okay, that’s four people, more or less (don’t you just love percentages? 11% of 40: 4.4 people…eh??? I’d be curious to know which part of that 0.4 person was in remission…)…oh let’s be generous, let’s say even five people in complete remission. But let’s look at the other numbers mentioned in the abstract: five patients developed what are called “serious adverse events” or SAE = gastrointestinal bleeding, delirium and glaucoma, two of these SAE patients left the study, in fact…and two other patients left at their own request…no details given as to why. Let’s add this up (math is not my forte, as you know, so you might want to double-check): five patients were affected by severe side effects, two left the study for unknown reasons, and four others were having problems such as asthenia, diarrhea and gastrointestinal bleeding. Now, according to my calculations, that’s eleven people with problems…compare that to the four, perhaps five, who achieved CR…out of a total of only forty patients…I don’t think I need to comment here…
  4. The abstract concludes that these preliminary results show that in sMM patients at high-risk for progression to active MM, delayed treatment is associated with early progression (median time 17.5 months) with bone disease, while so far Len-dex has been able not only to prolong the TTP (without any progression so far) but also to induce CRs with a manageable and acceptable toxicity profile. How “acceptable” was the “toxicity profile” for the smoldering patients who came down with delirium, glaucoma, gastrointestinal bleeding and infections? Uhm, just wondering…of course…!
  5. Last but not least. Celgene (the makers of Revlimid) was deeply involved in this study. In the abstract, check out number 21 on the list of hospitals/centers AND also the “Disclosures” section (=bottom of the abstract). You will find a list of 23 names: six, including the main author, are “Celgene Honoraria” recipients; two are Celgene employees (what the haaay???), and one belongs to the Celgene Speakers Bureau. So, let’s see: 9 people out of 23 are closely connected to Celgene…interesting…

This heavy involvement on the part of a pharmaceutical company made me suspicious right off the bat…And the following scenario popped into my head: if you saw a TV ad on a recently developed pesticide, would you trust the safety data provided by the pesticide company’s own spokespeople…enough to begin spraying this pesticide all over your vegetable garden? No, I didn’t think so…nor would I.

My own considerations: how would these patients be doing now if they had been given only curcumin and perhaps some of the non-toxic anti-myeloma plant-derived substances that I and others have been testing? You won’t get delirium or infections or glaucoma from curcumin or ashwagandha…

I rest my case.


  1. Margaret –you make some excellent points about this study. The numbers of subjects was small and the side-effects very worrisome. However, if this study were to involve a larger group and proceed for a longer period of time it might have some validity.

    It is a good thing to try and select out those with high-risk SMM vs low-risk SMM for obvious reasons. Many of these criteria revolve around M-spike and BM plasma cells and it is good to see that Free Light Chains (FLC) are now being included. The bone marrow PC as mentioned before is not terribly reliable because of the marked “spottyness” of plasma cell infiltration in the marrow in SMM. Unfortunately immuno-phenotyping and plasma cell labeling index (PCLI) are not performed at my hospital center.

    However I agree before we make any conclusions we need to see a much larger group followed for a longer period of time.
    Also I share your cynicism about the involvement of drug companies in these studies having seen how they repeatedly misuse or exaggerate data and other methods of convincing doctors and patients about how “great” their products are!

  2. Margaret,
    Thank you so much for this article. I never knew what was considered a high M-spike before! Now I know! I’ve asked my onc how high was too high but I don’t know that he knows! I’m so relieved to know mine is no where near 3 g/dL. Thank you for this valuable tidbit…made my day! Donna

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