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… 😉 

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 “standard of care.” 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: