[Toni]

Re: Risk of progression classification - smoldering myeloma?

by Toni on Wed Nov 05, 2014 9:36 pm

I was reading the Mayo risk stratification and I'm confused by something.

MGUS
"For MGUS patients, the following features are considered to be adverse risk factors: non-IgG isotype, M-protein concentration over 1.5 g/dL, and an abnormal serum free light chain (FLC) ratio (normal reference 0.26–1.65)."

SMM
"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."

Why is the reference range different for MGUS as opposed to SMM? Isn't the normal reference range the same regardless? SMM has a much higher upper range. That's the part I just don't understand. I would think that if the FLC ratio is outside of normal range, it would increase risk for either diagnosis?

I'd appreciate anyone's feedback on this. Thanks

[ciro]

Re: Risk of progression classification - smoldering myeloma?

by ciro on Sat Nov 08, 2014 4:30 pm

Hi Tony,

Information from the Mayo clinic article from 2008 (Dispenzieri et al, Immunoglobulin FLC ratio as an independent risk factor for progression of SMM) may help clarify this for you. The link to the article is:

http://www.bloodjournal.org/content/bloodjournal/111/2/785.full.pdf

They studied 273 SMM patients for a median of 12.4 years. Transformation to active disease occurred in 59% of these patients. They found that the breakpoint for predicting progression to multiple myeloma was a FLC ratio of 0.125 or less, or a FLC ratio of 8 or more. In their study, the group with a slightly abnormal FLC ratio of 0.25 or less,or 4 or more, had a similar rate of progression to those with a normal ratio of 0.26 to 1.65; this rate of progression was about 5% per year. For those with a ratio of 0.0312 to 0.125 or 8 to 32, the risk of progression was about 7% per year. For those with a markedly abnormal FLC ratio of less than 0.0312 or more than 32, the risk of progression was 8.1% per year. (These patients all had SMM, so they had a paraprotein level of 3 g/dl, and/or BMPC > or equal to 10, and no CRAB symptoms.)

As you are probably aware, once you are in the SMM classification (as opposed to MGUS), the risk of progression to multiple myeloma increases significantly. The degree of FLC abnormality defines the risk of progression more precisely.

The risk for MGUS progression was studied differently, and the effect of the degree of FLC abnormality was not specifically evaluated, at least in the recent classification.

I hope this helps.

[Toni]

Re: Risk of progression classification - smoldering myeloma?

by Toni on Sat Nov 08, 2014 5:02 pm

Thanks! That helps a lot. I just met with my oncologist yesterday and he also said he doesn't really worry until it gets a lot higher. It's good to know because the risk classification for FLC isn't super clear or obvious to everyone. I was trying to get a threshold.