[Maro]

Questions from France about smoldering myeloma

by Maro on Tue Apr 22, 2014 10:42 am

Hello everyone,

I have been reading through the forums for several days yet never daring to write because of my lack of knowledge (Especially after seeing how well informed some of you are! a wink to Multibilly )

My mother was recently diagnosed with smoldering myeloma in France. She underwent the classic tests: Blood tests, partial MRI of lower back and spine, complete body Xray.

In France they do not really function like in the USA. Over here, if there are any CRAB symptoms, they immediately go for induction therapy followed by a stem cell transplant (SCT), then maintenance therapy. I'm not entirely sure of the medicines they use, but i think it's VAD.

Revlimid is only used in case of relapse.

They are hesistant on whether or not to treat her immediately using the SCT because she is nearly 64 and the age limit in France is 65 for a transplant.

I really don't want to make a bad decision, so I am seeking your expertise.

Here is what we know so far:
- Bone marrow biopsy came back at 50%
- No CRAB symptoms yet (but a new MRI is to be done this week of the whole spine).
- Blood levels showed IgA lambda M Spike at about 10g/L, but another lab revealed a higher amount (is this possible?). There is also a small beta spike which was revealed.
- We are still waiting on the cytogenetics results.
- Her sedimentation rate is 135.

I believe she has had this condition for at least 2 years because I remember her making a blood test in December 2012 and her sed rate was the same, but we didn't look any further into exams at the time.

The main hope and question that arises is: Can she smolder forever considering the above results?

All your point of views would be so welcome ... I am so worried for my mom.

Thanks in advance.

[Multibilly]

Re: Questions from France about smoldering myeloma

by Multibilly on Tue Apr 22, 2014 11:25 am

Hey Maro,

Glad you reached out. I was clueless about this disease 18 months ago and all the great folks on this forum have taught me a great deal.

So, I am smoldering as well, and wonder about these issues all the time.

From a risk of progression standpoint, the easiest model to use without additional special tests is the Mayo model.

See this thread:

https://myelomabeacon.org/forum/formal-risk-of-progression-classification-for-smoldering-myeloma-t1542.html

The Mayo Clinic system has three criteria. The article described them as follows: "For SMM patients, the following features are considered to be adverse risk factors: ≥3 g/dL M-protein, an FLC ratio outside the reference range of 0.125 to 8, and ≥10% bone marrow plasma cells. At 5 years of follow-up, SMM patients with all three risk factors have, on average, a cumulative risk of multiple myeloma progression of 76% (median time-to-progression [TTP] was 1.9 years); for patients with two or one risk factors, the corresponding risk was 51% (median TTP, 5.1 years) and 25% (median TTP, 10 years), respectively."

So, you need to also be looking at your FLC ratio (which you probably have) to use this model.

A higher plasma cell percentage (your Mom's is admittedly fairly high) is also an added risk for progression https://myelomabeacon.org/news/2012/10/03/smoldering-multiple-myeloma-patients-with-high-percentage-of-plasma-cells-in-the-blood-are-at-increased-risk-of-early-progression/

Did you really mean to say 10g/L or did you mean 10g/dL for the M-Spike (10g/L = 1 g/dL, which is a very low M-Spike)? There's a big difference between these two numbers. Basically, you get the M-Spike from the Serum Protein Electrophoresis (SPEP) lab result, so I'm not sure how there can be two different M-Spike results from the same set of tests done on the same day?

Relating genetic mutations to risk of progression with SMM is still not a very clear science, but it will be good to know these results.

But you have to remember that there are lies, damned lies and then statistics You need to remember that everyone is an individual and may not follow the suggested trend of statistics. So, your Mom could smolder the rest of her life, even if she comes out being classified as having a high risk for progression.

Lastly, let me get this straight. Are you saying that if you have symptomatic multiple myeloma in France and are under age 65, that your only option is an SCT? They won't offer you drug-only treatment if you are symptomatic and under age 65??? Sacre bleu!

[Nancy Shamanna]

Re: Questions from France about smoldering myeloma

by Nancy Shamanna on Tue Apr 22, 2014 11:59 am

HI, I think that what Maro said was 'induction therapy' followed by a stem cell transplant. The therapy of VAD ... what does that stand for? I know that the 'D' would most likely be dexamethasone, but is the 'V' vincristine or Velcade? Velcade is often abbreviated as 'B' , i.e. bortezomib. It's all confusing, most of the time! But it's good that you wrote in Maro ...

I don't know anything about when to start treatment with smoldering myeloma from a personal point of view, but I wouldn't hesitate to use induction therapy if it is recommended. Then, you could take it from there about the SCT.

I don't think that there is an upper limit on SCT's in some other countries though. When I was having mine (at age 58), I did encounter another patient who was 70 doing one. His wife said that he was really very physically fit and thus was still a candidate even at his age. Hope that helps ... maybe you could get back here about the induction chemo regimen.

[Maro]

Re: Questions from France about smoldering myeloma

by Maro on Tue Apr 22, 2014 5:18 pm

Firstly, many thanks to the both of you for replying so promptly. It feels great to actually be able to speak to someone about all of this.

Multibilly: I will answer a few of the questions you've asked. I've uploaded this photo to help explain:

19-march-2014v2.jpg (84.53 KiB) Viewed 1304 times

Click the image to view with full vertical size.
Image is also available at http://un4.free.fr/test/19-march-2014

It is a picture of the M Protein spike results. As you can see the results are in g/L and not g/dL. There are two monoclonal spikes detected: One is in the beta at 9.5 g/L and the other in the gamma at 3.1g/L (total gamma 7.9g/L). Sorry, they are in French though

No info about FLC unfortunately.

In your example you mention a risk at 3g/dL which is 30g/L. So the spikes I'm refering to seem to be OK in comparison to the 30g limit?

Also: If she's had this for 2 years or more than we're on the right track considering TTP estimates?

What is odd though is that 1 month earlier she had this exam done in another lab and the results were slightly higher:

24-feb-2014.jpg (93.42 KiB) Viewed 1304 times

Click the image to view it full with full vertical size.
Image is also available here: http://un4.free.fr/test/24-feb-2014

With 14g/L in beta and 4.3g/L in gamma (the IgA one I guess).

She has been sent from one hospital to another and therefore the exams were repeated at approx 20-25 days interval.

She even did a 3rd exam last week (for which I don't have the results yet) in another lab belonging to the final place where she is being followed, which are specialized in cancers. The secretary told me the spike was higher but also said that the methods of estimation are different from one lab to another. Is this possible?

One final question: Does the sedimentation rate at 135 mean anything bad?

Regarding the stem cell transplant: Here in France they believe it is the best alternative. And considering her age they may want to do a SCT before age 65 to maximize chances of remission. For some reason, 65 is the limit in France because SCT is apparently a tough one to bare. SACRE BLEU indeed!

The thing is my mom is still so energetic, eats well, has no fatigue, still loves to cook for me She seems so 100% normal that it is so hard to succumb to the idea that she may be ill.

And that thought makes me feel so terrible.

Many thanks again for your feedback.

[Nancy Shamanna]

Re: Questions from France about smoldering myeloma

by Nancy Shamanna on Tue Apr 22, 2014 5:32 pm

Bonjour Maro, je vois que les résultes sont en français, mais les values 'normales' sont a la droite a la page. (The values are in French, but the normal ranges are given on the the right side of the page). Thus someone who is familiar with smoldering myeloma might be able to interpret the results!

I just asked the question about what the induction chemo was since in my opinion it could make a difference as to how well the myeloma is beaten back down! I had Velcade, so of course I am partial to that since it worked really well for me, but that of course is not always the case.

When I was diagnosed five years ago, the serum free light chain test SFLC was not yet in use here, so my diagnosis was made in a similar fashion to your mother's. Bonne chance!

[Maro]

Re: Questions from France about smoldering myeloma

by Maro on Tue Apr 22, 2014 5:39 pm

Hi Nancy, your French is pretty good !

The word "monoclonal" appears in the interpretation which indicates the M Spike degree.

Not fully sure about VAD, but i think its Velcade and dexamethasone. I was a bit under shock when the doctor told us all this, so lost my full concentration. I'm reading on some French sites that today they use Velcade - dex - thalidomide.

I'll get back to you on this one as soon as I see the doctor again with my mom. I will be more prepared this time to grasp the info.

But then again, if the MRI comes back clean, perhaps we will just undergo close observation (praying for that really with the hope of smoldering forever ... ).

[Beacon Staff]

Re: Questions from France about smoldering myeloma

by Beacon Staff on Tue Apr 22, 2014 5:50 pm

Thanks for sharing the additional information about your mother's situation, Maro. It will be helpful to all of us here as we try to help you interpret the results and offer you advice.

If you wish, we can revise your posting so that the images appear directly within it. We don't want to do that without your permission, but are happy to do so if it's okay with you.

On a couple of points that have been discussed ...

First, VAD generally refers to the combination of vincristine, doxorubicin (Adriamycin), and dexamethasone when it comes to myeloma treatment regimens. However, this regimen is unlikely to be used regularly in France any longer. It was a common regimen prior to the introduction of the novel agents Velcade and Revlimid, but now is not regularly used as induction therapy.

As Maro has pointed mentioned, combinations involving Velcade and dexamethasone, either doublets (Vd) or triplets (such as VTD, or perhaps Velcade-melphalan-dexamethasone) are more likely to be used for induction in France these days.

Second,what Maro has mentioned about age restrictions related to stem cell transplantation in France is actually not that surprising. One always has to be careful, of course, about making blanket statements. However, the general view that we hear among myeloma specialists is that stem cell transplants outside the U.S. are not common among patients older than 65.

In the U.S., on the other hand, transplantation is generally considered up to the age of 70, and even that is a very soft barrier -- it usually depends on a patient's general health.

[Maro]

Re: Questions from France about smoldering myeloma

by Maro on Tue Apr 22, 2014 6:03 pm

Hello Beacon Staff,

Many thanks for your offer to make the images appear directly within the post. Please feel free to do so.

Yes you are right about VAD being outdated. I'm reading on some french websites which speak more about VTD and compare it with CyBorD in the USA.
The website also says that Melphalan is used afterwards.
1) they use VTD or CyBorD (to be confirmed by the oncologist who I will ask next time)
2) They withdraw the stem cells from body
3) They go for Melphalan and you enter hospital in sterile room to avoid infections
4) They re inject your stem cells.

All french websites confirm 65 as maximum age.

The question they may ask themselves is wether or not to enforce treatment even if at SMM stage.

Their reasoning is as follows: Since SCT maximizes good response and, considering that in 1 year this won't be possible anymore, they prefer to do the SCT rather than take the risk of the multiple myeloma going active after 65 thus eliminating possibility of SCT and better response. Is this reasoning silly? All this is yet to be totally confirmed but it was suggested this way to me in a brief conversation...

[Multibilly]

Re: Questions from France about smoldering myeloma

by Multibilly on Tue Apr 22, 2014 6:16 pm

Maro,

First off, I'm not a doctor, and this is getting into some areas that I'm not that educated on. So, please double check all this with a multiple myeloma specialist and others on this forum.

All the numbers bounce around quite a bit, especially with MGUS and SMM. So this is normal. I'm therefore not surprised that any of the lab reports were higher the last time around.

Also, different labs will report different levels of many of the items you are discussing here. Different labs will also have different acceptable/normal ranges of numbers and can also use different units of measure. This is simply due to the labs having different test equipment from one another. This makes it really hard to track items over time, but that's just the nature of medicine.

If you have TWO distinct spikes, this might mean that this is a "bi-clonal gammopathy" of some sort. You really need a hematologist to accurately interpret these kinds of things....and I'm only guessing when looking at your SPEP results.

It also strikes me as a bit odd that your Mom has a 50% plasma cell burden in her bone marrow, but she has such a relatively low serum M-Spike. Maybe she is "oligosecrectory" (this is when one only secretes a small amount of the monoclonal immunoglobulins into one's blood). Does anybody else on the forum agree the M-spike seems low in comparison to the plasma cell percentage?

I would really be encouraging her to also get a Serum Freelite assay to measure the free light chains. If she is oligosecretory, you really need the Freelite assay to track the disease. Regardless, it's important to track the free light chain levels with any kind of multiple myeloma.

Did they measure her individual IgG and IgA levels? This might give you some further clues.

I really can't help you on your sedimentation rate question and tell you if this is a really high number, but it does increase when one has multiple myeloma.

So, I am admittedly throwing out some corner-case ideas here with biclonal gammopathy and oligosecretory multiple myeloma. I can very easily be completely wrong on all this, so please verify all this with a doctor and don't worry about what I am saying here. Just take these as ideas to investigate.

[Cheryl G]

Re: Questions from France about smoldering myeloma

by Cheryl G on Wed Apr 23, 2014 1:57 am

From what I'm seeing in the lab results, Maro, it looks like your mother's M-spike is in the beta region of the electrophoresis results, rather than the more common gamma region. Since the gamma results are within the normal range, I don't think this is a case of biclonal gammopathy.

Instead, your mother has an M-spike in the 1.6 - 2.1 g/dL range, depending on whether the spike in this sort of situation is measured based on the highest of the two beta components, or the total of the two components (I don't know).

There's some useful information about M-spikes in the beta region in this forum thread:
https://myelomabeacon.org/forum/m-spike-in-the-beta-2-region-t2360.html

I agree that it probably would be good to do both immunofixation and free light chain testing to get a better handle on exactly what the status of the disease is, particularly given the point Multibilly made about the bone marrow plasma cell percentage being relatively high.