A MGUS and SMM patient study on the possible impact of meditation in myeloma progression

A recent Patient Power video caught my attention a few days ago, but I was caught up in my andrographolide research, so I ignored it until today. It’s titled “Can smoldering myeloma progress to full-blown myeloma?” The obvious answer is yes, it can, of course. We know that.

Here’s the link to the video, which has other interesting things, too: goo.gl/e3ksk1

At one point, Dr. Raje talks about a Harvard project, called the , during which MGUS and SMM patients used meditation and mindfulness to try to stop progressing to full-blown myeloma. The study’s main purpose is to look at the genomic profile of these patients to ascertain if meditation could actually change the genetics of myeloma progression. Isn’t that something?

Dr. Raje adds, don’t worry too much about your disease…makes common sense. And perhaps, with the data they are collecting from patients right now, we will soon have actual proof that stress can have an impact on our progression genes….Wowsie.

We know that stress plays a big role in myeloma. We’ve known that for quite a long time (remember the 2008 Ohio State study on myeloma progression and norepinephrine, = one of the stress hormones? Exactly…). Certainly at times it isn’t easy to reduce stress levels, and I myself am not always successful (life complications, you know!). But I try! And meditation really does help…It helps even to just close your eyes for a few minutes and visualize a beautiful country or place you’ve visited, an event that made you happy, whatever.

You don’t necessarily have to follow a course to learn how to meditate (I never have)…although you could, of course! I’ve found my own meditation method, mainly based on watching online videos, and it works well for me. Anyway…

But this is the first time I’ve heard a conventional myeloma doctor mention MEDITATION as a possible way of avoiding progression. And I didn’t know about this project…Something to keep an eye on, for sure…

Dr. Raje  added that their results would be presented at ASH later this year. So we have a while to wait. However, I did find this abstract, published in the Journal of Clinical Oncology in May of last year: goo.gl/68nYeq

This link informs us that the experiment has been going on for a while now, and that this meditation program REDUCED STRESS, indeed DISTRESS, “in participants with intermediate or high-risk MGUS and SMM…”

Boy, I’d love to participate in something like that. A slight, er, obstacle is that I live across the pond…! Oh well!!! I’d also love to hear from someone who might be in the program…

Time for dinner…Have to rush off…Take care, everyone! 🙂

“The bone-marrow niche in MDS and MGUS: implications for AML and MM.” Part 2.

Back to the Dana-Farber study that I wrote about a couple of days ago.

The section titled “Therapeutic opportunities” is interesting. How to prevent progression, that is. As you can imagine, the chef’s daily special consists only of conventional treatments. For example, the authors make a reference to the Spanish study (Mateos et al) that I have repeatedly condemned here on the blog. The Spanish researchers–some with strong ties to the big pharmaceutical companies (hello???)–tested lenalidomide and dexamethasone on a group of SMM patients. The study claims to have prolonged progression-free survival and even overall survival in those patients…without ever taking into consideration QUALITY OF LIFE. Sorry, but I have no patience for statistical studies that play with people’s lives…

That said, the trend toward early intervention is clearly taking off, as the Dana-Farber study points out. Very unfortunate, IMO.

And there is no way to stop it, except that we, the patients, can say just say NO. Of course, if you have CRAB symptoms, that’s another matter. But, in the absence of the CRABs, WHY TAKE THE CHANCE OF WORSENING YOUR QUALITY OF LIFE?

Makes zero sense.

And there’s another thing that bothers me: where’s the proof that the overall survival of someone with SMM was extended thanks to these conventional treatments? Do the Spanish researchers have crystal balls that give them the exact times of death for their patients, both with AND without treatment? Oh, right, no, that’s what their STATISTICS tell them. Based on the patients’ “high-risk” data (see yesterday’s post).

I’m not saying that statistics can’t be useful in certain circumstances, mind you. But in these cases, when someone with no CRABs is deciding on whether to agree to early treatment, or not!, they can be harmful. If I had agreed to begin conventional treatments in 2005, I don’t know where I would be today (according to my former hematologist, I’d be dead…would have died in 2010…didn’t happen, OBVIOUSLY!!!…I’m still here, still splendid 😉 , still no CRABs, still no conventional treatments…).

Sorry for the rant. Okay, let’s calm down and try to understand the rationale of early intervention from the Dana-Farber study perspective. The researchers say that if the number of osteoblasts (bone-forming cells) can be increased in the early stages of myeloma, myeloma cells cannot proliferate. That’s good to know. There are non-toxic ways to do that, btw, but let’s keep to the study…

Mice that were injected with nanoparticles loaded with bortezomib before being contaminated with MM cells lived longer than non-injected mice. The researchers give another example in which early treatment of an antiangiogenic antibody was used on mice. Okay, but we’re talking about mouse models here. The reality, as the researchers themselves admit at the end of this paragraph, is that “…the use of antiangiogenic agents other than thalidomide and other immunomodulatory agents has not been shown to be successful in patients with MM.”

Not successful in patients.

So much for that.

Then there’s immunotherapy, which we have heard and read a lot about in the last few years. You may have heard about the anti-CD38 antibody known as daratumumab, which activates the immune system.

Anyway, it’s in this paragraph that I found a remarkable admission.

But first, let me say that ever since I joined online myeloma support groups, one of the key issues we discussed was what how to deal with our immune system. Should we stimulate it, thereby possibly stimulating our myeloma cells, too? Or should we avoid anything that stimulates the immune system? The consensus usually drifted toward the former approach. I wrote a post about this in 2013: http://margaret.healthblogs.org/2013/10/20/long-term-survival-in-myeloma-is-finally-linked-to-a-robust-immune-system-and-my-new-discovery/

I’ve had mixed feelings about it throughout the years, but my gut has always told me that it makes no sense to keep our immune system weak.

And here, in this paragraph, I finally have my answer (vindication!!!): “Indeed, trials involving these antibodies provide the first proof of concept that activation of the immune system has therapeutic benefits in patients with MM.”

After years of not knowing what to do, we finally know that having a strong immune system is GOOD.

Quelle surprise…not.

“The bone-marrow niche in MDS and MGUS: implications for AML and MM.”

Remember the post I wrote back in December 2014 about myeloma subpopulations and the bone marrow microenvironment? Probably not…so here’s the link: http://margaret.healthblogs.org/good-or-bad-for-myeloma/first-do-no-harm-myeloma-subpopulations/

The main point is that not much is known about the interactions between the myeloma subpopulations living in our bone marrow, how they compete for survival and so on…

Therefore, the only conclusion, in my opinion, is that going in with conventional bombs and blasting the heck out of this microenvironment doesn’t seem to be the best strategy for those of us with MGUS and SMM…certainly not until we know a LOT more about what goes on inside this complex and, I would add, delicate setting.

Luckily, there have been more studies on this topic since my 2014 post, including this recent Dana Farber one, titled “The bone-marrow niche in MDS and MGUS: implications for AML and MM.” A blog reader sent me the link (thanks!): goo.gl/Ew3K4A

The full study isn’t available for free online, but I was able to read it thanks to a good friend. Okay, let’s have a look at it…

We know that MM is preceded by MGUS and by an intermediate stage called SMM.

Progression, that is, the “clonal evolution” of myeloma, takes place between MGUS and MM. But, the researchers add, some of the characteristics of myeloma can be found, “at lower frequencies,” at the MGUS and SMM stages. For example, the gene deletions.

Therefore, they say, it is the development of neoplastic “subclones” in the earlier stages that probably leads to the progression to myeloma.

This development wouldn’t be able to take place without the help of the bone marrow microenvironment, which therefore must be targeted in order to prevent progression as well as increase the effectiveness of conventional treatments once the stage of MM has been reached.

As I was reading this study, full of technical jargon that I could barely grasp, I began imagining the bone marrow microenvironment as a marketplace where strong nasty myeloma hooligans live and operate in coexistence with other, not-so-harmful, silly myeloma characters, as well as a bunch of normal folks, our normal cells.

Problem: myeloma clones have the ability of turning the marketplace into a toxic environment that helps them grow and proliferate.

A lot depends on how the marketplace reacts to these attempted changes. If it is weak and yields to the MM hooligans, it will become full of “weeds.” If it resists, it will be full (well, perhaps not entirely!) of crowds of happy customers, what the researchers call a “physiologically useful crop of mature blood cells,” that is, normal blood cells.

Now, a NORMAL marketplace contains all sorts of custome…I mean, all sorts of cells, including osteoclasts, macrophages, endothelial cells and, don’t you love this one?, sympathetic neurons. Lots of different cells that live happily ever after in this lovely area of the body.

Too many details here…okay, we don’t need to know this stuff…skip skip skip.

Certain cells (the above-mentioned stromal cells, e.g., after they have gone over to the dark side) become responsible for helping myeloma develop. Furthermore, whenever myeloma cells initiate a disruption, things that should be sleeping (in technical terms: in a quiescent state) wake up (remember EBV?). Not good.

Disruptions also cause tumor suppressor genes, such as Rb1, to be…suppressed. Also not good!

The end result of all the disrupting and suppressing, without any reaction from the immune system, is that the BM microenvironment becomes myeloma-friendly, and MM stem cells can begin proliferating, helped along by processes such as angiogenesis (remember all my posts on VEGF?).

As you can imagine, the study doesn’t mention anything remotely non-conventional. But some of its findings are interesting, so let’s keep reading.

Ah, another thing occurs: immunosuppressive cells arrive in the marketplace and make such a ruckus that T cells and B cells are completely overwhelmed and can’t function properly. This means, of course, that myeloma cells are no longer being sought and destroyed by our immune system.

The study therefore gives us a lesson in progression. First and foremost, as we’ve just seen, myeloma cells learn how to avoid being annihilated by the immune system. They then create what the researchers call an “immunosuppressive environment” where the immune system defenders are no longer able to function normally. Other types of important cells present in this now-toxic environment are also affected, such as stromal cells.

When MGUS progresses to SMM and then MM, immunosuppression is one of the main culprits. In fact, I recently read a study that discussed this problem, concluding that patients with SMM whose other immunoglobulins—in my case, e.g., IgA and IgM—are suppressed are more at risk of developing myeloma. *

The questions are: can we stop this process? How? And…when?

In 2014 (and before), my opinion was to “watch and wait” for as long as possible. Until CRAB symptoms appear. My opinion hasn’t changed in all these years. Indeed, it hasn’t changed today.

“Watch and wait” doesn’t mean sitting around and moping and doing nothing but watch TV series all day long. It means being proactive, doing research, enjoying life, taking something that doesn’t have any toxic side effects and that has been shown at least in vitro to be anti-myeloma, such as curcumin. And so on. There’s lots of stuff we can do in this stage…

Okay, I think this is enough for one day. After almost falling asleepzzz myself, I decided to divide this post into three parts…or perhaps only two.

So…more on this topic tomorrow! Ciao!

P.S. The study also discusses the evolution from MDS to AML, but I didn’t really look at that part, of course, since it’s not my main focus…

* P.P.S.S. While it’s true that my IgA and IgM are suppressed (barely “alive,” in fact!), it’s also true that they’ve been pretty much at the same tiny level for years now. So yes, I am in the high risk category BUT I am still here, leading a normal life, no CRAB symptoms…

Living proof that being at “high risk” doesn’t have to be as scary as it sounds…right?  🙂 

“Long-term follow-up of curcumin treated MGUS/SMM patients – an updated single centre experience”

In an email I received yesterday, Dr. Terry Golombick notified me that her team’s most recent article has been  published in the Journal of Hematology and Medical Oncology. It is available for free online…just click here: goo.gl/cEP93h

keep calm and turmeric onAhhhh. Wonderful…absolutely wonderful.

Wonderful, because finally…FINALLY (!!!)…we have a long-term look at a GROUP of MGUS and SMM patients taking curcumin. These are those who participated in the Australian MGUS/SMM study and who “continued to take curcumin over a number of years, of their own volition, even though the studies in which they were participating are complete.”

So this is a “long-term follow-up of 13 MGUS/SMM patients who have been taking curcumin (at a dose of 4 -8 grams daily) for a period of 3-9 years.”

Only one patient, who had cardiac amyloidosis (!), went on to full-blown myeloma and is currently undergoing conventional treatments. The rest of the patients are doing quite well, some better than others…anyway, you can read all the details in the report…

I really hope that this report will encourage more and more centers to start giving curcumin to their MGUS and SMM patients and, why not?, to their MM patients as well. At this point, I could go into a tirade about the short-sightedness of conventional medicine, but, at least for now, I’d rather look at the positive side, which is the publication of some CASE STUDIES, like the one concerning my blog reader D., and this Australian one.

I would like to end this post by stating that we all owe a large debt of gratitude to dedicated researchers like Dr. Golombick who have overcome all sorts of obstacles (I’m sure of that!!!) to help patients like us have the best quality of life possible, for as long as possible…

To all the Golombicks of the world: thank you, thank YOU, THANK YOU!!!  🙂 keep calm and watch and wait

By the way, let me remind you that Dr. Golombick and her team have set up a useful website for all of us who have a type of blood cancer. I’ve talked about it here on the blog, but just in case you missed that post, here is the link: https://www.watchandwaitbloodcancers.com/

KEEP CALM AND…

WATCH AND WAIT!!!!!! 

IL-1beta involved in progression from inactive to active myeloma

I found out about this wonderful little gem from a couple of myeloma list friends (thank you both so very much, D & D!). It’s an editorial (see: http://tinyurl.com/b7z59z) on a Mayo Clinic study titled “Targeting the Pathogenic Role of Interleukin 1beta in the Progression of Smoldering/Indolent Myeloma to Active Disease,” (abstract: http://tinyurl.com/acqlkb; full study: http://tinyurl.com/akqd4r). I haven’t read the full study yet (I will read it tomorrow…it requires more attention and care than I can give it at the moment: ). Both can be found in the February 2009 Mayo Clinic Proceedings. At any rate, I am basing my post on the editorial (shorter and easier to read than the full study…).

 

47 patients, all at the inactive or smouldering myeloma stage (=my stage) but at high risk of progression, participated in the Mayo study, which was carried out between 2002 and 2007. The idea was to answer the fundamental question: WHAT THE HECK makes folks progress from inactive to active myeloma?

 

Apparently what happens is that IL-1beta, another of those beastly pro-inflammatory and pro-angiogenic cytokines, induces marrow stromal cells to produce large amounts of interleukin 6 (IL-6), thereby promoting the survival and expansion of the myeloma cells

 

The researchers confirmed their theory that reducing the activity of IL-1beta does, in fact, significantly increase progression-free survival (PFS) in these high-risk patients. This is extraordinary!

 

And now read this: blocking IL-1beta reduces IL-6 as well as the proangiogenic chemokine IL-8, therefore the use of IL-1beta-blocking strategies may result in new standards of therapy for high-risk patients with SMM/IMM. WOWIE!!!

 

In the study, all the smouldering myeloma patients were given anakinra, an IL-1beta inhibitor that is used for the treatment of rheumatoid arthritis and autoinflammatory diseases. I should add that 25 patients were also given a low dose of dexamethasone. Two of the them remained stable for about four years, and in fact, at the time of this writing, progression to active disease has not yet occurred […]. Since, as I mentioned, I haven’t yet read the actual study, I don’t know what happened in the other 23 cases…

 

Another significant excerpt from the editorial: In the study, patients with a decrease in CRP levels were more likely to have stable disease, confirming that effectively blocking IL-1beta (using CRP levels as the marker for IL-1beta activity) can halt progression to active myeloma.

 

Halt progression to active myeloma…aaaaah, how sweet those five little words sound…

 

Hmmm, but WHY am I so excited that I could skip and dance all around my study (probably will, as soon as I post this)?

 

Because, drum roll!, CURCUMIN INHIBITS IL-1BETA!!! (See, e.g.: http://tinyurl.com/b7yr3j and http://tinyurl.com/bgqud4) There are heaps of studies on this topic, in fact, probably much much better than the above two that I found after a lightning search…but right now I am too elated and, well, in a bit of a hurry–it’s almost dinnertime–to see if I can find the perfect one…I just want to go ahead and post this bit of good news!

 

More good news: curcumin is not the only one. Here is a list of the other natural IL-1beta inhibitors that I have found thus far (ah, but my quest has only just begun, so there will probably be more…):

 

1.     quercetin (strongly) http://tinyurl.com/dfy39r and http://tinyurl.com/c6v3np

2.     omega-3 http://tinyurl.com/c2ksmg

3.     genistein http://tinyurl.com/cbtpsr

4.     EGCG http://tinyurl.com/andmdj

5.     resveratrol http://tinyurl.com/cmnayw

6.     ellagic acid (on my to-be-tested list) http://tinyurl.com/bgvutf

 

I will stop here because I want to go give my husband a big bear hug…and do another little jig of joy around the room on the way! Yippity yippity doodle! Evvaiiiii, grandeeeee!!! 🙂