A friend (thank you!) sent me a case study last week. You can view the abstract here: http://goo.gl/baWTd It actually turns out to be quite a bit more than a case study, as we will see…
Without further ado, let’s hop right into the full study. The central character, in this first part, is a healthy 72-year-old white man with smoldering myeloma diagnosed 6 months ago, a man who had an 11-year history of MGUS. Coincidentally, his MGUS was diagnosed in 1999, which is the year of my own MGUS diagnosis…
In 2009, he had a bone marrow biopsy (=BMB) that revealed 40 % plasma cells, and his free light chains ratio was 2.44. He also had a test called fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), which showed a mild FDG uptake in the sacrum. The result, however, was: no bone lesions.
Two months later, during a follow-up visit, his M-protein had increased from 4.4 g/dL to 4.9. Since he complained of lower back pain located in the sacrum and left iliac bone areas, he had a second FDG PET/CT. This time, focal lesions were found in those two areas…
Now, okay, I know that I have a suspicious nature, but doesn’t it seem a bit too coincidental that this patient had TWO of these tests in what seems to me to be an amazingly short period (TWO months)…and the second FDG PET/CT revealed focal lesions? These, by the way, can be benign, I read. Well, forget it, let’s keep going…
You can read some details about FDG PET/CTs here: http://goo.gl/gEkdM Scroll down to “Operation,” where you can read that a short-lived radioactive tracer isotope mixed with FDG, which is an analogue of glucose (hmmm and double-hmmm) is injected into the patient’s bloodstream…After about an hour, this tracer finds its way into the tissues of interest…
Now scroll down to the “Safety” paragraph. Yikes! Now, I don’t have a whole lot of time to do research on the FDG PET/CT topic today, but I just read that it is essential to avoid unnecessary and repetitive imaging or excessive re-staging in patients who may have already been imaged previously at the same or other locations (see: http://goo.gl/hIctB).
Food for thought. Or not…
At any rate, getting back to our case study, the patient was diagnosed with multiple myeloma and began treatment with lenalidomide/dexamethasone with partial response after 3 cycles. The authors don’t mention him again…
The rest of the study is an interesting analysis of previous “progression” studies, beginning with those showing how active myeloma is preceded by MGUS and SMM. We have already discussed this topic, so there is no need for me to summarize this part.
Here is something for us to chew on: the change from MGUS to active myeloma is not sudden, the authors say. Rather, several overlapping oncogenic events within plasma cells and the marrow microenvironment accumulate from normal plasma cells through precursor disease to advanced multiple myeloma. These cellular changes can be seen in almost all MGUS patients, and from MGUS onward, and include hyperdiploidy and primary immunoglobulin translocations at the 14q32 locus. Cyclin D dysregulation is also mentioned as a very common early event.
Next, we get into a rather long overview of risk criteria (skipskipskip)…notably, the Mayo Clinic criteria and that grrrrr! outrageous Spanish SMM chemo study. Interestingly, the authors prefer the Mayo Clinic system, which is more readily available and allows the clinician to spare patients with low-risk MGUS from undergoing a bone marrow biopsy. Couldn’t agree more!
Then we get to the “Imaging” part: In current practice, imaging in MGUS and smoldering myeloma fulfills 2 roles: ruling out progression and monitoring for early complications.
The authors point out that the skeletal survey is relatively insensitive and nonspecific for detecting myeloma-related bone disease (=the lesions have to be quite evident to be picked up by an x-ray)…but it also only requires a relatively small dose of radiation to perform on the whole body.
They then describe the Whole-body low-dose multidetector row CT, which can detect lesions smaller than 5 mm. This test has negative consequences, though = heaps of radiation. Okay, neeeext!
Whole-body MRIs are more effective than skeletal surveys, they say. That reminds me–I have had a few MRIs (only of my spine), but without any contrast liquid…Let’s never forget that gadolinium, frequently used as a contrast agent, makes MM cells proliferate…!!!
Now for the “Clinical Management” part. MGUS patients apparently have a higher risk than healthy folks of developing thrombosis and fractures. I have read about those studies, but have actually not…read them (to my recollection). Concerning thrombosis, the study to read is: http://goo.gl/Be0SC. For fractures, see http://goo.gl/0qRKP The full texts are available online…for free, which is helpful. (You might have to click on “manual download.”)
Going on…ah, here is an interesting statement: Treatment trials for MGUS are problematic, as patients are relatively healthy and most patients have a low lifetime risk of progression, especially when other causes of death are taken into account. Thus, an ideal treatment would be nontoxic and directed toward patients with high risk of progression. “Nontoxic,” huh? Hmmm, I just might have a few ideas…! Hehe.
The subsequent paragraph is not as upbeat. It concerns my own condition, smoldering myeloma: Early treatment strategies for smoldering myeloma are particularly attractive as the rate of progression to multiple myeloma is quite high. Okay, while these strategies might appear “attractive,” the authors add that all the SMM chemo clinical trials have failed so far. Indeed, if anything, the smoldering patients in these studies were worse off than when they started…
I was rather surprised to read the authors’ words of caution concerning that SMM Spanish study: […] it is unknown whether treating patients with smoldering myeloma improves overall survival or quality of life, as such data are not yet available. Well, you already know what I think about that infamous study…about all the toxicities that these poor patients are enduring…Talk about unnecessary…to say the least…! Uffa! Okay, Margaret, enough…
The authors conclude that Aimed at preventing progression, smoldering myeloma could be treated as a chronic disease, with relatively benign maintenance therapy used to control the malignant clone. Alternately, highly active therapy could be used with the goal of cure, although this may prove challenging in the context of current treatment options. However, to responsibly perform any such trial, well-designed correlative studies should be performed to assess the theoretical possibility of unexpected long-term adverse events or selecting for more aggressive disease. Well, I like the bit about “benign maintenance therapy”…In Margaret’s world, curcumin and a few other things fall into that category…
The study ends with a few notes on “future directions.” And read this: even smoldering patients at the highest risk for progression, with detectable disease on advanced imaging will likely become candidates for early treatment strategies, likely with agents not currently available in the clinic. “With agents not currently available…” Well, you don’t have to read between the lines: that sentence rules out the Spanish SMM study…
And hey!, I didn’t say it…Two researchers from the Center for Cancer Research at the National Cancer Institute did…so there.
The above-quoted paragraph continues (and this is how the study ends): However, such trials should be cautiously designed to assess progression-free and overall survival, as high response rates may not correlate with survival and prolonged stable disease may provide key benefit to patients.
PRECISELY. ESATTAMENTE. Let’s focus on prolonged stable disease…
It appears clear (to me, anyway) that asymptomatic smoldering patients should NOT undergo any conventional treatment, even if they are in a high-risk category. Yes, of course that is just my opinion. However, based on the Mayo Clinic criteria, I am in the highest-risk-for-progression group. So this evening I am taking a stance, once and for all: I would rather go bungee jumping (yikessss!) every single day than have chemo at this point. It’s too bloody risky…
Paraphrasing my hero, Prof. Aggarwal (I don’t recall the exact quote, sorry, and have to go prepare dinner now…), it’s not really such a good idea to go and poke a sleeping tiger…
