[jhorner]

How to measure disease progression in smoldering myeloma?

by jhorner on Fri Jul 11, 2014 1:09 pm

Hello,

My oncologist had indicated that I won't likely ever have another bone marrow aspirate or biopsy because the percentage of plasma cells that qualifies asymptomatic disease is so high at 60%, that an increase in BMPc wouldn't change the diagnosis. So my question is, how is disease progression officially determined?

I read that it is determined by SPEP and increasing M protein, but there are so many patients that are non-secretory that it doesn't seem like a reliable indicator.

My M-spike has been consistent for many years at about 1.3 g/dl, but my FLC ratio is ever changing. I am IgG lambda and I am only having blood work every six months and these are the last three reads - newest to oldest.

K/L ratio - 0.30
K/L ratio- 0.51
K/L ratio- 0.85

Is this indicative of progression, or are there other criteria to consider? What are we looking for when we get our regular blood work and should I be getting blood work at shorter intervals?

Best,
J

[Dr. Adam Cohen]

Re: How to measure disease progression in smoldering myeloma

by Dr. Adam Cohen on Sat Jul 12, 2014 12:24 pm

Disease progression in smoldering myeloma can be measured in 2 ways:

1. Biochemical progression, meaning rise in the M-protein in serum or urine (or in the involved free light chain if your myeloma doesn't make an intact M-protein). True non-secretory disease is only seen in 2-3% of patients, but in this case following bone marrow biopsies to see the percentage of plasma cells would be needed.
2. Clinical progression, meaning development of one or more of the CRAB criteria (elevated calcium, kidney dysfunction, anemia, or bone lesions).

If CRAB criteria develop, then by definition it's active myeloma and treatment is needed. So you should be looking at blood counts, serum creatinine and calcium, and bone imaging periodically during your follow-up visits.

For biochemical progression, there are strict definitions published by the International Myeloma Working Group: A 25% rise in serum or urine M-spike, confirmed on at least 1 subsequent test, that must also be at least an absolute increase of 0.5 g/dL for a serum M-spike, and at least 200mg for a urine M-spike. For those without intact M-spikes, a 25% increase in the involved free light chain, that is at least an absolute increase of 10mg/dL (100 mg/L) is required.

So, for instance, since your M-spike is 1.3, it would need to increase to at least 1.8 on 2 occasions to be considered progression.

However, even if this occurs, this does not always mean that treatment must be started immediately if there are no CRAB criteria present. Many patients with early biochemical progression can still be watched closely (perhaps every 3 months instead of 6), and only if there is a persistent continued increase would we consider treatment. This is an individual decision to be made with each patient and his/her oncologist.

Hope this helps.

[jhorner]

Re: How to measure disease progression in smoldering myeloma

by jhorner on Sat Jul 12, 2014 1:56 pm

Thank you Dr. Cohen,

Your response is very helpful indeed. I do have one additional comment regarding the M-spike being used as a measurement for disease progression.

I had a bone marrow aspirate to rule out amyloidosis due to sudden onset of bilateral carpal tunnel syndrome and a swollen spleen. That test showed the disease had progressed to smoldering, 12% plasma cells, but still my M-Spike had not changed. So it seems at least possible to have disease progression without having it reflected in the M-spike?

Best,
J

[Dr. Adam Cohen]

Re: How to measure disease progression in smoldering myeloma

by Dr. Adam Cohen on Sun Jul 13, 2014 10:07 am

I would be careful about over-interpreting small changes in the plasma cell percentage. Marrow involvement with myeloma can be patchy, and the percentage can change slightly based on the quality of the specimen or even the interpreting pathologist. So a change from say 6% to 12% may not necessarily reflect progressive disease, but rather these other technical factors.

Amyloidosis is somewhat of a special case. It is not part of the typical CRAB criteria, but is a disease where organ damage can occur despite low levels of plasma cells, and without major changes in M-protein.

If amyloidosis is suspected, then serum free light chains should be checked (since it's the light chain that turns into amyloid), and a biopsy of the suspected involved organ or a surrogate site (such as abdominal fat) should be done to look for systemic amyloid deposits. This would require treatment if present, even if the M-protein levels have not increased.

Given its rarity, it may be worth getting an opinion with a myeloma/amyloidosis specialist if things remain unclear.

[jhorner]

Re: How to measure disease progression in smoldering myeloma

by jhorner on Tue Aug 19, 2014 10:46 am

I seem to have an intact M-protein measuring 1.03 - 1.3 for the last 8 years with MGUS / SMM but my lambda free light chains increased from 1.38 mg/dl to 2.51 mg/dl in one year.

Is the M-spike reliable or should the FLC be used?

[Jonah]

Re: How to measure disease progression in smoldering myeloma

by Jonah on Tue Aug 19, 2014 2:12 pm

jhorner - Are you sure about the units you used for your lambda free light chain levels? You list them as mg/dl, and you say that you are IgG lambda. But the lambda free light chain levels you gave (1.38 to 2.51), if the units you listed are correct, are way below the normal range for lambda FLC levels.

See, for example, this posting by Dr. Shain, which has some FLC normal ranges for one major lab (Quest):

https://myelomabeacon.org/forum/free-light-chains-reference-values-units-t3225.html#p18244

He lists reference ranges of:

Kappa: 74-295 mg/dL
Lambda: 32-156 mg/dL
Kappa/Lambda Ratio: 1.3-2.7

[jhorner]

Re: How to measure disease progression in smoldering myeloma

by jhorner on Tue Aug 19, 2014 4:13 pm

Thanks Jonah! I read the thread you attached but I double checked and these numbers, including the unit of measure, are coming straight from the report - copy and paste....

Free Light Chains, Serum - Final result - Thu Jul 10, 2014 1018

Component Results
Kappa Free Lt Chain 0.78 0.33 - 1.94 mg/dl Final
Lambda Free Lt Chain 2.51 0.57 - 2.63 mg/dl Final
Kappa/Lambda Ratio 0.31 0.26 - 1.65 Final

Now I really need help! Irregardless of these numbers, my primary concern is that my M-spike is unreliable and not really an intact M-spike. In the last year I have developed immunoparesis (with both uninvolved immunoglobulins) and, though my IgG is in range, I was told that few of these immunoglobulins are "normal" and I'm on IVIG infusion therapy.

It looks like (and feels like) SMM is progressing, but the M-spike is stable. If there are strict definitions for progression (surrounding M-spike alone), as indicated by Dr. Cohen, this is very concerning because I will not receive proper follow up or treatment.

[Jonah]

Re: How to measure disease progression in smoldering myeloma

by Jonah on Tue Aug 19, 2014 4:30 pm

Okay, now I'm confused. Here's a reference I found that seems to confirm the reference ranges that you listed:

http://labmed.ascpjournals.org/content/40/6/363/T1.expansion.html

Reference Intervals for Serum Free Light Chains

Free kappa 3.3 – 19.4 mg/L [or 0.33 - 1.94 mg/dL]
Free lambda 5.7 – 26.3 mg/L [or 0.57 - 2.63 mg/dL]
Kappa/lambda ratio without renal impairment 0.26–1.65
Kappa/lambda ratio with renal impairment 0.37–3.1

which is from this article:

Siegel et al, "Serum Free Light Chain Analysis for Diagnosis, Monitoring, and Prognosis of Monoclonal Gammopathies," Lab Medicine, 2009, 40, 363-366.

Perhaps the reference ranges Dr. Shain provided were for a different free light chain test?

In any case, it looks like your lambda free light chain levels are within normal range. We can discuss the other issues you brought up later in the discussion. Just wanted to get this correction up.