[Mark46]

Smoldering or active (symptomatic) multiple myeloma?

by Mark46 on Sat Feb 10, 2018 2:55 pm

My Mom has already been diagnosed with smoldering myeloma. She has IgG lambda with the FGFR3 / MMSET translocation - t(4;14) and monosomy 13. I just recently had her records sent to me and quite frankly, the numbers have me upset. Her oncologist is using the W.H.O. criteria and will not initiate therapy until all the criteria have been met because he feels that there is no cure.

She has been getting tested every 3 months and I will present the information in the following order for all tests presented here. Oldest is # 6 and most recent is #1 ( 6 - 1). I.e. - all # 3’s have the same test date.

Bone Marrow Biopsy, Clot and Aspirate (#6) -
Finding - mildly hyper cellular marrow with interstitial infiltrates of plasma cells constituting approximately 15% of the marrow. Flow cytometry reveals 3% IgG lambda monoclonal plasma cells. F.I.S.H. shows unfavorable prognostic indicators. Iron stains are 2+.

Bone Density Reports (#5 & #1)
#5 - Based on reading at the femoral neck, spine and left hip - all T- scores are in the normal range.
#1 - Low bone mass based on the left third radius T-score ( neck, spine, & hip are normal).

Fine Needle Aspiration - Abdominal Fat Pad ( #3 & #1)
#3 - Negative for amyloid. Both Congo Red and Diff Quik are negative.
#1 - Negative for amyloid. Both Congo Red and Diff Quik are negative.

Immunofixation, Urine (#2 & #1)
#2 - 2 monoclonal lambda light chains detected
#1 - 2 monoclonal lambda light chains detected

Gamma Globulins ( #4 , #3, & #2)
#4 - (IGG=1927-H) (IGA=103) (IGM=42)
#3 - (IGG=2033-H) (IGA=57-L) (IGM=<25-L)
#2 - (IGG=5158-H) (IGA=<40-L) (IGM=<25-L)

Protein Electrophoresis Serum (#4, #3, #2 & #1) In the past she was biclonal but spike 2 has disappeared.
#4 - ( spike 1=1.33)
#3 - ( spike1=1.43)
#2 - ( spike1=3.36) (Gamma globulins=3.50) (Protein/SPEP=9.30) (A/G ratio=0.72)
#1 - ( spike1=3.78) (Gamma globulins=3.90) (Protein/SPEP=9.80) (A/G ratio=0.68)

Kappa / lambda Free Light Chain ( #4, #3, & #2)
#4 - (lambda=291) (kappa=9.6) (k/l ratio=0.03)
#3 - (lambda=284.1) (kappa=7.7) (k/l ratio=<0.01)
#2 - (lambda=999.2) (kappa=5.6) (k/l ration=<0.01)

Select Blood Tests (#4, #3, #2 & #1)
#4 - (WBC=6.8) (HGB=13.1) (HCT=39.4) (PLT=235)
#3 - (WBC=5.6) (HGB=12.8) (HCT=38.6) (PLT=265)
#2 - (WBC=4.4) (HGB=11.2) (HCT=33.4) (PLT=221)
#1 - (WBC=5.2) (HGB=12.3) (HCT=36.5) (PLT=213)

Summary
#6 = Bone marrow aspirate
#5 = Bone density report
#4= Gamma Globulins, Protein Electro. Serum, Kappa/ Lambda, & Select blood tests
#3=fine needle aspiration, Gamma Glob., Prot. Electro., kappa/lambda, Select blood tests
#2=immunofixation urine, Gamma Glob., Prot. Electro, kappa/lambda, Select blood tests
#1=bone density, fine needle aspiration, immunofix.urine, Prot.electro., Select blood tests

Thanks.

[Multibilly]

Re: Smoldering or active (symptomatic) multiple myeloma?

by Multibilly on Sat Feb 10, 2018 10:04 pm

Hi Mark,

Welcome to the forum.

In general, you don't treat smoldering myeloma (which is what your mother appears to have based on what you've presented here). I'm smoldering and my specialist wouldn't likely start treatment based on what you've presented here so far. The exception to this rule is that some high-risk smoldering patients have elected to participate in clinical trials that are experimenting with the early treatment of smoldering myeloma patients. But be aware that the evidence that these early treatment approaches have any long term benefit is not at all clear yet. Also, keep in mind that these early treatments involve drugs which can have negative side effects, so doctors don't take the initiation of treatment lightly.

However, doctors almost always start treatment when a patient meets one or more of the "CRAB" criteria (increased calcium level, kidney (renal) failure, anemia, and.or destructive bone lesions). Some doctors "may" also consider starting treatment if you meet one of the new Myeloma Defining Events (MDEs). See the following article for a more complete explanation of these terms:

https://myelomabeacon.org/news/2014/10/26/new-multiple-myeloma-diagnostic-criteria/

So, given that your mother doesn't have an exceptionally high free light chain ratio or bone marrow plasma cell percentage, her hemoglobin isn't in the anemic range, and her t(4;14) and monosomy 13 mutations are not generally considered to be high risk (see article link below), this leaves you with needing to look at her serum calcium level (to check for increased calcium level), serum creatinine level (to check kidney function), and imaging studies (to check for destructive bone lesions) to see if she meets any of the remaining CRAB criteria or the MDE criteria of more than one focal lesion on an MRI that is at least 5mm or greater in size to see if treatment may be warranted.

https://www.msmart.org/mm-treatment-guidelines.html

Hope this helps you to better understand where her doctor might be coming from.

[Mark46]

Re: Smoldering or active (symptomatic) multiple myeloma?

by Mark46 on Sat Feb 17, 2018 3:18 pm

Thanks for your reply, Multibilly.

According to this summary of multiple myeloma diagnostic criteria, two criteria have been met: plasma cells in the bone marrow (above 10 percent) and free light chain ratio of less than 0.01.

Some more facts about Mom:

1. She had monoclonal gammopathy of undetermined significance for 20+ years before progressing to smoldering myeloma. Right before progression to smoldering myeloma, her second M-spike disappeared and her gamma globulins became abnormal.

2. She has a complicated health history which includes ovarian cancer, breast cancer, stroke, hypertension, asthma, rheumatoid arthritis among others.

3. She has seen many specialists regarding her frequent upper respiratory infections, low back pain, constant headaches, and joint and bone pain. All tests and treatments have failed to diagnosis or help these symptoms. Plus, her oncologist has been made aware of these.

4. It's my understanding that t(4:14) with monosomy 13 may carry an intermediate risk while others suggest that this is high risk.

All I know is that since her myeloma tests have become abnormal her health has declined. And as they continue to show increasing numbers, she has more complaints. However, her blood test indicators (hemoglobin, etc) have remained within the normal range.

Thanks,
Mark

[Dimamar]

Re: Smoldering or active (symptomatic) multiple myeloma?

by Dimamar on Sun Feb 18, 2018 1:17 am

Mark,

So good of you to pay such a close attention and take care of your mom!

Looks like she does not have "CRA" criteria, but as far as "B," was there at least an x-ray, if not MRI, PET/CT, or PET/MRI done to check for bone lesions?

She, however, does have one MDE, as her ratio of lambda/kappa is 999/5.6 = 178 (reversing ratio for convenience to not deal with decimals)

However, #2 was not, 284/7.7 = 36, although it says <0.01.

Certainly, trend in M-spike and kappa-lambda ratio is not good.

As far as treatment, while a kappa-lambda ratio of 178 denotes active multiple myeloma according to the IMWG criteria, if your mother's oncologist does believe treating is warranted yet, I would agree and wait some more to see if the result repeats.

Best of luck!

[Multibilly]

Re: Smoldering or active (symptomatic) multiple myeloma?

by Multibilly on Sun Feb 18, 2018 9:59 am

Hi Dimamar,

Good catch on the numbers. I missed that #2 entry for the free light chain ratio.

I think it will be key to know what the free light chain ratio is from the most recent #1 tests in order to see if that high number is holding steady or was a fluke. In addition to both us recommending looking at some recent imaging results, I would also re-emphasize the need to look at her kidney function (e.g. creatinine, etc) to see if the high lambda free light chain level from test #2 is starting to affect her kidneys.

[Mark46]

Re: Smoldering or active (symptomatic) multiple myeloma?

by Mark46 on Wed Feb 21, 2018 8:11 am

Thanks for your replies.

All her myeloma diagnostic tests (SPEP, FLC, etc) are in the abnormal range (for the past few tests now) and increasing while her routine blood tests remain in the normal range but toward the high end. She has only been sent for bone density tests and the most recent was abnormal. it showed signs of bone loss not due to osteoporosis or osteopenia.

She has been getting frequent upper respiratory infections (1x/month, sometimes more) and com­plaining about low back pain, pain in her joints and muscles, headaches, lethargy, abdominal pain, nosebleeds, ear and eye issues. Yet her routine blood tests still are in the normal range but trending higher.

Thanks, Mark.