Treat so-called “high-risk” smoldering myeloma…Yes or No?

My (predictable) answer is “NO, absolutely NOT.” Not until you begin having CRAB symptoms. But first things first…

I began writing this post last week, then I just had too many things to do so I didn’t finish my draft. Then, yesterday morning, before going to work, I came across an article by Dr. Brian Durie (I don’t think I need to explain who he is!) making some of the points I had already made in my draft, BUT from the point of view of a world-famous hematologist.

So I decided to cut my draft in half and give you the link to Dr. Durie’s piece:¬†

But, of course, I still have some comments to make… ūüėȬ†

First, though, a bit of background. In a recent trial, the ECOG trial that Dr. Durie refers to in his article, lenalidomide was administered to so-called “high risk” smoldering myeloma patients. Based on the trial results, the authors state that lenalidomide “may” delay progression to active myeloma.

Yes, this was a “big” SMM trial, the biggest to date, anyway, with 182 participants…but, according to Dr. Durie, “Of the 180 patients in the ECOG trial, only 13 with HR-SMM received treatment with lenalidomide. Though their outcomes were improved versus observation alone, this is an extremely small number of patients as a basis for a ‚Äústandard of care.‚ÄĚ In addition, the remaining patients (the vast majority of them) were those with lower-risk SMM, and they did not achieve benefit with treatment. This is important on many levels, not least because the criteria for the diagnosis of HR-SMM are currently in flux.”

There are many points of discussion here. First of all, based on data from only 13 patients, the authors recommend that lenalidomide be offered to patients with “HR” SMM. Based on data, I repeat, from only 13 patients, the authors suggest that lenalidomide should become a “standard of care” for the so-called “high-risk” smoldering myeloma patients…

Does that make sense? Not to me…and not to Dr. Durie.

Secondly, why the heck were lower-risk SMM patients included in this study??? Ooooh, that makes my blood boil.

And it begs the question: why did these patients agree to be included? This just goes to show that we (patients) need to be more informed, much more informed, about what we might be getting into…I’m not saying those patients weren’t informed, perhaps they were, but boyohboy, if my hematologist suggested that I participate in a study testing a conventional drug with potentially very bad side effects, you can imagine what I’d say…

And, thirdly, what Dr. Durie says about the “criteria for the diagnosis” of “high-risk” SMM is something I’ve been saying over and over again in various posts on this topic, and that I’d made in my draft last week, too. And that is why I want to put it in BOLD lettering: the experts themselves do NOT agree on the definition of “high risk smoldering myeloma.

And hey, if THEY can’t agree, how can I trust them to tell me that I need to start taking a drug that might give me some serious adverse effects and bring my quality of life down a notch or even several notches? Sure, it might not. I might react perfectly well to the drug and be perfectly fine. But nobody can tell me that taking lenalidomide is as safe as taking a vitamin pill. There are a number of potentially very bad side effects, including the onset of other types of cancer (as well as blood clots, severe liver problems, etc.).

And in fact, according to Dr. Durie, “Among treated patients, 40% came off treatment due to toxic adverse events.”

40%. That’s quite a large number, don’t you think?

Interesting note. Dr. Durie also writes: “If a patient with SMM progresses, what is that? Is it myeloma? Maybe, maybe not.” Precisely. Nobody knows. When you begin fiddling with SMM, things can get very muddy. Did you progress to active MM because of the cancer or possibly because of the drugs you were taking? There are so many factors involved in progression…most of them, still unknown.

One last…rant. Whenever I read about patient trials, I always ask myself how these folks are doing, how lenalidomide (in this case) has affected their quality of life, if at all. I mean, what’s the bloody point of surviving for a longer time, or of delaying progression to myeloma, if you’re going to spend most of that time in a hospital, fighting off infections, skin rashes, blood clots, or…well…or worse?

Studies don’t provide us with that vital bit of information…

And they should.

P.S. The full study is available online for free, so you can take your own look at it and draw your own conclusions (I have only skimmed it…no time to do more that that right now…but I will read the full shebang soon!):

P.P.S.S. The basic information is also contained in this Mayo Clinic press release, dated October 26, 2019:


  1. Treating too early simply beats up the patient and starts the clock ticking on wearing out the drug. Same thing with maintenance after SCT – unless you need it (numbers are rising), you are mostly making yourself miserable to the tune of $1,000/month co-pay and cutting into the time Revlimid et al will work for you in the future. Although, an aside, now that we are in the future at our house we just discovered the fine print – if Revlimid is costing you more than 3 percent of your income, EVEN IF you are above the income cutoff for assistance, you can get an exemption and Celegene will cover your co-pay. We’ve paid for most of this year, but now – whoopee – we are getting it at no charge!!!

  2. Hello guys
    I have not officially been diagnosed yet but have a high kappa lambda ratio which is just over 100. I know this will be seen as mde and treatment should be started but I have no CRAB symptoms. The heamatologist said that this would be considered smouldering under the old guidelines. I do not want treatment obviously and have started my curcumin regime. I also take Boswelia and black seed oil.
    My question is can the kappa ratio be elevated for any other reason other than mm?
    I saw an interesting talk by Doctor Rajkumar from the Mayo clinic regarding treating smouldering patients. He said something about the involved free light chain being elevated due to dimerization. Also he stated that the new guidelines should not apply if the ratio has been elevated over 100 for many years but remained stable without CRAB.
    My question the doctor was how do you know I havent been at this level for years? His answer was I dont but as you are a few points over the 100 ratio you need to start treatment.
    It just doesnt seem right…please let me have your thoughts.


  3. Margaret,
    I appreciate your comments and post so very much. I’m one of these “new” so-called HR-SMM based on the new definition. My doctor has already inferred that I will probably be qualifying for the ASCENT trial using combination of Darzalex¬ģ (daratumumab) + Kyprolis¬ģ (carfilzomib) + Revlimid¬ģ (lenalidomide) + dexamethasone some time next year right here in Charlotte, NC. This is why I’m trying to bring my numbers down with curcumin so I am just SMM again and not have to face that decision. It would be nice to just be SMM for 5 years and get on the other side of these trials and see some of those “later after” results you were discussing. I guess I’m going to be banking a lot on my curcumin protocol to keep my numbers low so I don’t get enticed by the “free” drugs in clinical trial. Kind of ironic if I keep the numbers down and totally miss the close of the trial enrollment without qualifying and then progress later and have to fund the cost of treatment on my own. If I have to do that I’ll just start treatment when I’m full-blown MM like everyone else. I’m committed at this point and plan to join you in the long term SMM group!! Thanks again for leading the way.


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