[sirfer009]

Re: MGUS, smoldering, or active multiple myeloma?

by sirfer009 on Thu Oct 13, 2016 9:23 am

Thank you to the both of you for the responses. I'm highly optimistic after seeing these results as well as the comments that you made. I'll keep you posted as the results come in and I will keep on top of the issues. I can't tell you how grateful I am that you are helping me understand what all of this means.

[mikeb]

Re: MGUS, smoldering, or active multiple myeloma?

by mikeb on Thu Oct 13, 2016 10:19 am

Hi JPC (and Sirfer009),

I think the "Not Observed" in Sirfer009's M-spike results is simply the indication that the normal value for an M-spike is for it to not be observed. I don't think it means that the M-spike was not observed for Sirfer008.

That's my reading of those results, at least.

Mike

[JPC]

Re: MGUS, smoldering, or active multiple myeloma?

by JPC on Thu Oct 13, 2016 10:30 am

Thanks very much, Mike. Your explanation makes sense.

For sirf, one more point occurred to me after posting. It may be the case (hopefully) that you have many many years until you reach smoldering (even better, if at all), however, in your research, please look at the following. In a sense, it is much better to catch it now. Many patients learn about multiple myeloma based on a broken spine, or similar conditions. There is active research right now into treating before the multiple myeloma turns active. I am in no way suggesting go out and start treatment now. That would not at all make sense for MGUS. Results of clinical studies going on now, and new studies, will be out in the next several years. I am suspecting that for high-risk smoldering, that at some point, it will be determined that treatment with Darzalex, or some combination with Darzalex, will be able to get most smolderers to minimal residual disease (MRD) negative, and delay for many years progression to active multiple myeloma. I think you have plenty of time to do your research, but this is a research suggestion from me.

Good luck to you.

[sirfer009]

Re: MGUS, smoldering, or active multiple myeloma?

by sirfer009 on Fri Oct 14, 2016 5:40 pm

Well, I received the call no one ever wants to hear. My plasma cells are at 17%. I'm being referred to Moffitt for a stem cell transplant. The good news is that I'm only 47 and I've always loved a good fight!

Thanks to everyone that posted, and I'll let you know how things go.

[Multibilly]

Re: MGUS, smoldering, or active multiple myeloma?

by Multibilly on Fri Oct 14, 2016 7:13 pm

Hi Sirfer,

To be clear, a 17% bone marrow plasma cell percentage in itself would not normally be reason to pursue a transplant. Unless you have some sort of a myeloma defining event (meet one or more CRAB criteria, > 60% bone marrow plasma cell percentage, > 100 free-light-chain ratio, focal lesions on an MRI, etc), your diagnosis would be smoldering multiple myeloma.

If you are smoldering, you typically either watch-and-wait for the disease to potentially progress to multiple myeloma, or you may consider drug-only treatment (Revlimid, Kyprolis, Darzalex, Empliciti, PVX-410 vaccine, etc) in a clinical trial. However, it would be pretty unheard of for a smoldering patient without some sort of extenuating circumstances to get a transplant.

Please see this link for the requirements for a multiple myeloma diagnosis that would cause one to consider the option of a transplant:

Rajkumar, SV, "New Criteria For The Diagnosis Of Multiple Myeloma And Related Disorders," The Myeloma Beacon, Oct 26, 2014

[sirfer009]

Re: MGUS, smoldering, or active multiple myeloma?

by sirfer009 on Fri Oct 14, 2016 8:07 pm

Multibilly,

I totally understand what you are saying. I haven't gotten the tests back. The only thing I know is from the phone call. The doctor said he is recommending the stem cell treatment and referring me to the transplant team at Moffitt. I can't understand it either, considering how low all of my other numbers are. The one thing I do know is that I will get a second opinion from Mayo before anything is done.

As always, you have solid advice that is based on reasoning. Thank you for that!

[JPC]

Re: MGUS, smoldering, or active multiple myeloma?

by JPC on Sat Oct 15, 2016 10:01 am

Hi Surf:

Just to reiterate what was said by Multibilly, in the case of my wife, she was still considered MGUS at a 20% level, and when it went to 30%, she was considered smoldering. So as I mentioned, I am not a doctor (and Multibilly as I recall has also admitted the same). I cannot say for sure that there is not some good reason to go forward; perhaps there is. I would say a second opinion would make sense, but in terms of the "ABC's" of multiple myeloma, having an autologous stem cell transplant without CRAB symptoms and below 20% in the bone marrow, at first blush, does not seem to make sense to this person who has done some general reading on the subject.

Good luck to you.

[sirfer009]

Re: MGUS, smoldering, or active multiple myeloma?

by sirfer009 on Sat Oct 22, 2016 7:03 am

I have more news, although I'm not sure what it all means.

I had my first appointment with the myeloma doctors on Tuesday. They've given me an initial diagnosis of smoldering. I've got another bone marrow biopsy along with a PET scan on Tuesday. I don't think I'll have another diagnosis until then.

The test results from Tuesday (October 18, 2016) have posted. Several of my numbers are up. Here are the results:

Hemogram Results

Preliminary ANC > 1.5 K/uL
Mean Cell Volume 96.1 FL 80.3-94.0 FL

Differential % Results

Neutro Auto % 58.7 %
Eos Auto % 2.2 %
Basophil Auto % 1.1 %
Mono Auto % 8.6 %
Lymph Auto % 28.8 %

Routine Chemistry Results

Creatinine 1.0 mg/dL 0.7-1.3 mg/dL
Calcium 9.7 mg/dL 8.6-10.2 mg/dL
Total Protein 8.7 gm/dL 6.6-8.7 gm/dL
Albumin 4.1 gm/dL 3.5-5.2 gm/dL
Total Bilirubin 0.60 mg/dL 0.00-1.20 mg/dL
Alk. Phosphatase 26 U/L 40-130 U/L
Iron 56 ug/dL 59-158 ug/dL
TIBC 255 ug/dL 250-450 ug/dL
T3, Free (Triiodothyronine) 3.0 pg/mL 2.4-4.2 pg/mL
Folic Acid, Level 3.4 ng/mL 4.8-24.2 ng/mL

Electropheresis/Immunofix Results

Serum E/P Albumin 4.7 g/dL 3.5-5.2 g/dL
Serum E/P Alpha 1 0.2 gm/dL 0.2-0.4 gm/dL
Serum E/P Alpha 2 0.7 gm/dL 0.5-1.0 gm/dL
Serum E/P Beta 0.6 gm/dL 0.5-1.1 gm/dL
Serum E/P Gamma 2.5 gm/dL 0.7-1.5 gm/dL
Serum E/P M Spike 2.2 g/dL 0.0-0.0 g/dL

Immunoglobulins Results

IgG 2977 mg/dL 700-1600 mg/dL
IgA 52 mg/dL 70-400 mg/dL
IgM 54 mg/dL 40-230 mg/dL
Kappa Quant Free Light Chains 77.43 mg/L 3.30-19.40 mg/L
Lambda Quant Free Light Chains 7.90 mg/L 5.71-26.30 mg/L
Kappa/Lambda Quan FLC Ratio 9.80 0.26-1.62

Immunology / Serology Results

Beta 2 Microglobulin 1.5 mg/L 0.8-2.2 mg/L
C Reactive Protein 0.21 mg/dL 0.00-0.49 mg/dL

My free light chain level is up over 2.5 points in 2 weeks, and my IgG is up as well. I have a feeling that the new biopsy is going to show that my plasma cells are also on the rise.

My myeloma doctor disagrees with my original oncologist. He wants to have a wait and see approach and wait for something to show up that meets the CRAB criteria before starting any kind of treatment. That to me seems rather dumb. Why wait until the cancer does damage? The odds of going from smoldering to active seem rather high to me because my numbers have jumped so much in just two weeks.

Anybody have any opinion on this?

[Multibilly]

Re: MGUS, smoldering, or active multiple myeloma?

by Multibilly on Sat Oct 22, 2016 8:17 am

A few things.

1. These are not big jumps in your IgG and kappa free light chain levels. Also, two data points don't make a trend.

2. Keep in mind that bone marrow plasma cell percentage measurements are very hit-and-miss affairs due to how unevenly the disease can be distributed throughout one's skeleton. Your actual disease burden could be completely unchanged, yet you can come up with very different bone marrow plasma cell percentage readings from one biopsy to the next.

3. You could easily attribute the changes to normal fluctuations in one's numbers and/or the differences in values between labs (my M-spike consistently measures about 30% higher in one lab versus another lab, - my IgG value also varies about 700 mg/dL between the two different labs). See my marker histories in this forum post to get an idea of how much an M-spike and IgG can naturally vary over time. These kinds of fluctuations seem to be more common and pronounced in MGUS and smoldering myeloma patients, according to my onc.

In my opinion, you really need a few more data points from the same lab to see if your numbers are truly trending upwards.

4. To be treated early in a high-risk smoldering multiple myeloma clinical trial is certainly an option (you are just barely in the high-risk category based on the markers you've posted thus far; see this article for how one determines high-risk smoldering myeloma these days). But I wouldn't personally say that not being treated early is "dumb". When I was first diagnosed with what is now known as "high-risk" smoldering myeloma, two specialists told me that I would be symptomatic in a year and that I would be back to see them for a transplant at that time. It's been 5 years since my diagnosis and I'm doing just fine ... and I never went back to those doctors. This is a good article that touches on some, but not all of the issues surrounding early treatment of smoldering multiple myeloma.

Manasanch, E., et al, "Smoldering Multiple Myeloma: Special Considerations Surrounding Treatment On Versus Off Clinical Trials," Haematologica, Dec 2014 (full text of article)

[JPC]

Re: MGUS, smoldering, or active multiple myeloma?

by JPC on Sat Oct 22, 2016 5:52 pm

Hi Sirf:

I have an understanding of a case of progression from MGUS to smoldering to active, based on my wife's history (a single case, but I have tried to read a lot generally, as well). In your case, I did pick up on the pretty darn low plasma cell percentage, which indicated to me more towards the MGUS, and I was even surprised you were called smoldering, but of course, I am not a doctor. Myeloma is tricky, and what you have over and above what my wife had was light chain involvement, at this time.

On a very high level, in M-spike dominated multiple myeloma, the light chains go out of whack, but only because they are driven out of whack by the overpopulation of the heavy chain clone. If the multiple myeloma also is directly causing a light chain imbalance, which does impact a minority of patients at the early stage, then it's a more complicated situation that I am less willing to comment on, because I do not understand it, other than the fact that it is more compli­cated.

I agree with everything that Multibilly has stated. The state of the art right now is that they do not treat smoldering off of clinical trial, so I think the word "dumb" is probably not the exact right word. I do hear you, however, and appreciate the sentiment. Multiple myeloma is the only cancer with a "watch and wait" protocol. For every other cancer, catching it as early as possible, and intervening, is key. This goes back to the uniqueness and "trickiness" of multiple myeloma.

Doctors who are considering treating multiple myeloma earlier note that one issue is that, as it grows, there is an increased tumor burden, that it reaches a "critical mass" of cancer, that the body cannot deal with. So if the issue was only that, watch and wait probably makes sense. It has also been pointed out, however, that multiple myeloma turns to active multiple myeloma, that it "morphs" into something worse. Before it morphs, it is more benign, and possibly more easily dealt with by available treatments, to push it down to a lower level, when its in the state where its easier to deal with.

This is an issue under active study. I do not think you have to "pull the trigger" on an approach in the next month or two (hopefully, a lot longer). You should track your status very closely. If it does start to trend up, you should be knowledgeable regarding the best available option to you.

For smoldering, I think Revlimid maintenance only was pretty marginal. I believe that there was results this year that for high-risk smoldering, Revlimid-dexamethasone was a good deal better. There are more trials out right now, for instance involving Darzalex. The somewhat stronger approaches may drive down the level of smoldering (or MGUS) so much that the onset of active multiple myeloma may be delayed by many, many years.

So good luck to you. I am glad its still less than active multiple myeloma, and hope it stays that way for a long time.