Oh, I’m fuming. I’m frothing at the mouth. I’m verrrry upset.
This morning I read, then re-read after lunch, the “Myeloma Beacon”‘s January 13 interview with Dr. Ola Landgren: http://goo.gl/iZizX By the way, my comments will make much more sense if you read the interview first, so please click on that link before proceeding…
Okay, here goes. I suppose it’s no secret that I’m strongly (and that’s a bloody understatement!!!) opposed to “early treatment.” From what I’ve read and been told by MM specialists, early treatment does NOT bring any benefits and could in fact make things worse. Much worse.
Of course, I’m referring to chemo treatment.
Perhaps some valid treatments might appear on the horizon at some point in the future…treatments for smoldering folks, guaranteed not to poke what we MMers call “the beast”…guaranteed not to worsen our quality of life…But that is not the case right now.
If you’ve been following my blog since early 2010, you may remember that on a number of occasions I’ve railed against the infamous SMM-chemo trial led by a group of Spanish researchers…a bunch of whom, including the head researcher Dr. Mateos (!), have verrrry close ties to Celgene Corporation, the multinational drug company that just happens to produce one of the drugs tested in the trial (see http://goo.gl/7DUUZ).
Hmmm. Talk about going on bright red alert… 😕
I just asked Stefano if he would buy a camera from a company that tests its own products…no independent testing…well, you can imagine his reaction…!
He also remarked, “Hey, but just think…if Celgene were able to expand its market to SMM folks…”
$$$
But the Celgene connection is not the only reason I’m outraged that such a trial even exists…(FTR: the Spanish study has gotten bigger; it now includes 119 patients–57 in the treatment arm, 62 in the non-treatment one, average age = 61 and 65, respectively.)
HOW ARE THOSE SMOLDERING FOLKS DOING? AND HOW WERE THEY DOING BEFORE THE TRIAL?
In the Beacon interview, Dr. Landgren talks about “progression-free and overall survival benefits.” But what I would like to know is this: what about quality of life? What about toxicities? You may recall that some of the SMM patients enrolled in the Spanish study presented at ASH 2009 developed some “serious adverse events” or SAEs (for an overview of “SAE,” see http://goo.gl/JqBAH). A couple of patients left the study because of those SAEs.
That is not acceptable. NOT.
Okay, I just looked up the ASH 2011 (updated) Spanish paper: http://goo.gl/gzVSA Oh sigh, I don’t have the time or will right now to examine all those numbers, but apparently there were no G4 toxicities (remember that G5 = death!), “just” a bunch of G3s. Now, I don’t know about you, but after reading that list of G3 consequences, I began getting a case of the itches. And then I read that “tolerability is acceptable.” Uhm. For whom?
I repeat, HOW ARE THOSE SMOLDERING FOLKS DOING? AND HOW WERE THEY DOING BEFORE THE TRIAL?
I would like to avoid repeating or paraphrasing what I’ve already written on the Spanish study. But I would like to discuss something said by Dr. Landgren that shocked me right out of my socks this morning. He says that he doesn’t like the expression “high risk” (well heckaroni, WHO does?!!!)…not for smoldering patients, not for multiple myeloma patients. In his opinion, the former (= the high risk SMM people) should be called “early myeloma” patients.
WHAAAM! Well, that hit me right in the gut. I mean, we all know what a huge emotional impact words can have on us, right? Shit. (Sorry.)
“Early myeloma” may sound okay to someone who is healthy, but I doubt that it sounds okay to any of us smoldering folks. Truth be told, I don’t care one whit for “smoldering,” either…I prefer this sweet sound of “inactive.” Words…gee…gotta be careful…
But that was only my first reaction. Then I saw red. After all, statistics tell us that only a relatively small percentage of SMM folks progress to active myeloma. Okay, as far as I know, we don’t have any specific progression statistics about “high-risk” SMM folks, but (again, as far as I know) this expression was invented by the Spanish Celgene-connected authors. Well hey, I’m in that high-risk group, but my QOL is very high, and I haven’t progressed yet. And it’s now been more than six years. (Ooops, knocking on wood…) 😉
Now, a few not-so-bad things came out of this interview.
- What Dr. Landgren says about treating “early myeloma” does make sense. That is, treat cancer in its early stages instead of waiting for things to get worse. (But, I repeat, NOT with current treatments! It’s too risky for us = the smoldering hot group. Why take the chance?)
- When Dr. Landgren was asked if he thought early treatment in high-risk SMM folks would be the best option, he answered: “nobody knows at this time.” (Hah, no kidding. And did you notice that he repeated “nobody knows at this time” TWICE during the interview?). So he wouldn’t give lenalidomide and dexamethasone to his own smoldering patients. Good to know.
But then…in the next breath he says (and this sent my socks shooting way out into my neighbor’s yard…) that in the spring of THIS YEAR he is going to supervise a SMM study that will examine a treatment regimen involving eight cycles of carfilzomib, Revlimid, and low-dose dexamethasone followed by Revlimid maintenance for a minimum of one year. We are using carfilzomib instead of Velcade in order to increase the efficacy and at the same time reduce the side effects, in particular peripheral neuropathy […].
What the…?????? 😯
Luckily, he added, Let me stress again, however, the need for more studies before any of these ideas start to be considered “standard of care.” Bloody hell.
Reading stuff like this drives me bonkers. I mean, doesn’t it make much more sense to invest money in developing a curcumin analog (or another promising, similar, non-toxic, natural substance with proven anti-MM effects)? There is so much scientific evidence (and now, so many anecdotal accounts, too…Mine is not an isolated case anymore, thank goodness!) to back up the potential usefulness of curcumin in the treatment of myeloma at any stage, also in combination with chemotherapy (by the way, I refuse to use the expression “novel agents”…but that happens to be the topic of a post that I began writing a few days ago, so I won’t go into it now. Stay tuned…)
Where was I? Ah yes. We need to find a way of giving curcumin an “umph!,” that’s all. Luckily, there are a few research teams that are investigating that right now…And I wish them LUCK! Now, that is the sort of trial I would love to participate in…a curcumin analog trial…
Well, I tell ya, my stomach is tied in a knot. The “early myeloma” business really upset me…And even now, close to dinnertime, after spending a lovely sunny cold morning planting tulip and other bulbs in our back yard, I am still a bit upset, which means I’m not thinking as clearly as I should be, and that I might possibly have misinterpreted a few things that Dr. Landgren said during the interview. In fact, I probably shouldn’t even go ahead and publish this post right now (Stefano suggested two minutes ago that I stop writing and join him in the kitchen, where he’s making dinner…), but I would really like to get some feedback from you guys…What do you think?
Let me conclude by asking: whatever happened to the concept “Early treatment is a very bad idea”?????
P.S. Sorry for any repetitions…no time to go over this draft…must go help with dinner…ciao!
Write on, Margaret.
I joined you in the stomach twisting! Medical researchers working for pharmaceutical profit is not a new phenomenon, for sure, but whatever happened to the vow to ‘do no harm…?” Jeeeez
Great gut reaction Margaret. I was encouraged by Dr Landgren’s “slow down” message, ie don’t jump to conclusions, we need more study on this. Some of us have a hard time with “watch and wait”. As a prostate cancer survivor I am particularly attuned to this. I want to do something. It took surgery and radiation a year later to free me from prostate cancer. My initial hematologist told me that for my stage of MM, without treatment, I had 3 years to live (a*sh*le). And then I went to Moffitt and they said there was no treatment necessary at this time for my SMM. Huh? Is that a 3 year death sentence? Second opinion at Dana Farber in Boston who tell me I’m MGUS, not SMM, and I should NOT participate in any clinical trials. That is the difference, I believe, between high risk and low risk, and I think some are already practicing the distinction in the academic medical community. I personally will adhere to my belief that raw fruits and veggies can “save” me when accompanied by curcumin and a few other supplements. Don’t put that toxic stuff in my body … as long as I am not getting much worse. But if other patients hate the waiting and want this disease to be cured, I wish them well and recommend they sign up for these clinical trials. I hope we have more good outcomes than not, and I hope someone gets “cured”. As for me, I was rejected from a clinical trial of the DKK-1 antibody by Novartis (generally non-toxic, low risk) because I was not “high-risk” for progression into MM. I will stick with my holistic approach as long as this disease lets me maintain my quality of life. On the other hand, if I had a del(13q) or other high risk factors with worsening blood/urine tests, I might be looking for a better way to stave off this disease and want to take a chance for a better life in a clinical trial. Many thanks, Margaret, for keeping us up to date and for your insights. You are an invaluable resource in the MM community.
so it is the farmaceuts that have the money…and will finance trials that could be profitable to them… so if you want to do research…and have no independent funding, the options are bleak…either explore yet another way to use the same ingredients (which for the drug company is far more profitable than investment in research of even new drug company agents) or find some other source to finance the work. As early myeloma…we are all prospective ‘customers’ to put into the balance sheet…..bleah
but inspiring about the tulips!
Margaret, I was so upset Shan I read this last night, I wished I had your phone number to wake you so we could screech out our objections.
I started to prepare bullets for you so I could send to you by email so if you agreed, it might speed things up. Even if you prefer to write your own from scratch it might have made me feel better to vent it out.
I only have an iPad here, no printer, and was at the same time organizing to break outta here for 2 weeks I Miami. So going back and forth between his article and FB and my wp got to be too much. Worse yet, the more I read and wrote, the angrier I became. Overshadowed the good of the article (eg I am happy this group is no longer ignored, I just do not want them to have to be nukes like me).
Odd that you also noted that phrase being repeated twice. I was so certain he repeated it many more times, I was making that one of my points. “nobody knows at this time”. I thought my iPad was broken when I did a search and found only 2.
I will try to compose myself, and pull some of my points from FB and my notes. I think it is impotent to note that at least two of us had such a visceral response. My poor hubby begged me to stop ranting. It means that even though we may not be able to explain as lucidly as always, ther is still our instinct, which told us that something was rotten in the town of ..
Ok, time for dinner. A is calling.
More later
On the one hand, I can appreciate the concept of treating a so-called early myeloma patient if — and this is a big IF — a cure seemed likely and accessible. Indeed, this seems to be one of the hopes that Landgren is promoting: treat the disease at an early pre-malignant stage when the cancer burden is relatively low.
On the other hand, this remains only a concept: I don’t think we know whether such circumstances are present or not.
The other thing that is unclear to me is exactly what Landgren defines means by high risk SMM. I looked at some papers by Landgren, and I think — but am not certain — that it means having the following 3 characteristics: abnormal FLC; > 10 percent bone marrow involvement; and non-IgG type. Is that correct? Or is it something else, like certain results from gene-expression profiling or cytogenetics?
Finally, his suggestion of using an aggressive approach to treat SMM — carfilizomib, revlimid, and dexamathsone — is supposedly low-toxicity, but I am not sure. And again — what is the patient left with when there is a relapse? Velcade? Thalidomide?
I am, of course, biased, because as an SMM subject (for now) with an active and healthy life, I would greatly prefer a vaccine or immunotherapeutic approach — not full-blow therapy with twice-weekly infusions and the slippery medical slope that follows.
Hi all, I leave comments here once and awhile and I am an avid, daily reader of Margaret’s Corner. I am also a patient of Dr. Landgren’s at the NIH. I am enrolled in his landmark(non-treatment) study of the progression of myeloma from its precursor states of MGUS and SMM. I will always be beholden to Dr. Landgren because when I first got my diagnosis (August 10, 2011), the first myeloma expert I went to was already sizing me up for an allogeneic SCT without even thoroughly reviewing my case!!!! I went to the NIH, where he classified me as SMM, and I never went back to the other so-called expert thanks to Dr. Landgren. He has always been transparent with me and I personally believe he has no commercial interests at all. Also, he written and talked about second malignancies related to, I believe, lenalidomide and that exposure would certainly not make him a friend of the pharmaceutical industry. Any way these are just my feelings from ground zero. Terry
It seems that the response to Landgren is a little over the top and quite emotional when it comes to ‘early myeloma’.
Another immune disease that was not treated early enough was HIV. Initially, physicians waited until the Tcell count was way to low to begin therapy, and many many many people died of AIDS in the late 70s & early 80s. Then Dr. David Ho at Cedars Sinai, had what was considered a radical idea at the time and that was to treat AIDS early in the disease process. As a result, the disease is now known as HIV and does not progress to AIDS, for many patients.
Both HIV and MM are immune diseases one of the Tcells and the other of the Bcells, respectively. Perhaps, the prevailing view of non-treatment for SMM is not the best course of action in terms of survival, if one considers it is likely early myeloma cellular changes..
In this regard, what Dr. Langren is proposing makes a lot of sense, to consider this as one disease and the severity of it as it progresses should not be labelled as if they were separate diseases by calling it MGUS, Smoldering and MM…what we actually have is a disease that is consistently progressing to its finally stages. Ergo, ‘early myeloma’ would be accurate and early treatment would definitely move us from incurable disease to a chronic disease which is manageable.
The only problem I see is how to determine those patients who are most likely to progress and at present those individuals are being labelled ‘high risk’ SMM. There is suffiicient clinical data to predict that those individuals will go on to full blown MM.
Therapy today is no where as toxic as it was when aklylators were the primary agents of choice.
If we can treat those individuals at the ‘early myeloma’ stage then perhaps they have a real shot at long term survival vs. those who wind up with all the chromosomal abnormalities due to disease progression that enable & sustain the cancer as an aggressive and invasive tumor with minimal survivor.
Perhaps, there are those who would prefer the term pre-myeloma to early myeloma…just as we say pre-diabetic and pre-hypertensive.
But treatment before it progresses is certainly a reasonable course of action to consider if increasing survival is the primary goal.
Just my two cents.
Thank you to Margaret and others for getting this topic out there to us for discussion.
After being told by the heamo for the past 6 yrs that there is nothing can be done to stop the progress of Myeloma,I was shocked into self-action by a bad test result (now SMM), I then discovered the brilliant “Margaret” (thank god),her logic and knowledge is second to none for mine.
After discussion with my GP I commenced on curcumin (now 3+2+3gms/day + liquid fish oil morn&night)plus other antioxidants. I also consulted a wholistic GP for advice on how to “tune up” my bodies biological system so it has the best possible chance to fight for its self and just maybe with the help of curcumin stop the progression of this disease. Also discussed this approach with the heamo who had no objections but was clearly sceptical,did not want to get into discussion about vitamins,minerals,enzymes ???(healthy bodies)
I no longer assult my system with “damaging” food I only take in “productive” food and water and natural nontoxic substances,I have joined the natural health society,I am learning much. My next test due end feb 2012.
The statement from “the medical expert” in this story is “no one realy knows”(or something like that)HOW TRUE !!!! so like Margaret I would like to know WHY does the medical profession limit potential treatments to “toxic drugs only” ???? (other than for the profit motive)It seems to me that it could be negligence for a MD not to take a whole of body approach to patient treatment and hopefully healing, if only!!!
Before we go off the deep end, remember, all the supplements in the world Won’t Cure this thing…we need real drugs and you need clinical trials (God bless the volunteers that willingly put themselves at risk so we can gather the DATA we NEED to make rational decisions…not emotions. Also there are many forms of Myeloma (based on Gene data being developed..again by heroic researchers). You may be a lucky one with a less aggressive form, but there are others with extremely high risk genes (High risk meaning very short Overall Survival with current treatment options, usually less than 3 years). These people may benefit greatly from early treatment before their genes mutate further. We need both…good studies on alternate medicines as well as drug clinical trial. To paint one “competitive” approach as “evil” or not as “pure in character” as the other is purely irresponsible! Don’t you think the supplement manufactures are just as interested in “proving” their products to make an evil profit..or are they doing it out of the goodness of their hearts.
Just My Opinion.
One of the odd things about Bob’s numbers is that his genetics CHANGE. The del at 13 is… gone! What was earlier called a 4:14 translocation is now a 4:11 (that one may have just been a mistaken report, I don’t know for sure). I guess these genetic abberations are not inherited, so I guess it is logical that they could further change since they changed to begin with. But it puts a different slant on the risk assessment. The patient could go from one category to another, over time. Whether it is the result of treatments or just a fluke I don’t know. But Bob smoldered for , lik, ten minutes, after his DX and was into active myeloma. Had to hold off treatment due to back surgery. The radiation of a Plasmacytoma may have kicked off the plunge to active, it kicked off the further deterioration of the back (I hypothesize that the plasmacytoma had already eaten the marrow and was all that was holding the vertebra up. when it was gone, the bone gave way).
Julie are you saying Bobs genetic del (13g) changed?
yes, I believe it did. They no longer say he has a deletion at 13, unless I misunderstood. I will ask about it again, but that was what I heard.