How would you approach therapy for a patient with smoldering multiple myeloma whose light chain ratio has increased to greater than 100 over several years in the absence of any other myeloma-defining events?

I struggle with this as well, but the serum free light chain ratio (SFLC-R) at 100 is not magical for a patient that you've been following. An SFLC-R>100 is predictive of an increased risk to develop CRAB criteria of 60-90% w/in 2 years. This prediction is refined by measuring 24hr UPEP using a bar of 200 mg/24hrs as the big predictor based on Mayo Clinic data.

But the focus in this question is regarding evolving monoclonal proteins. The Mayo Clinic also reviewed this retrospectively in smoldering myeloma in 2016. They defined an 'evolving monoclonal protein' as a >10% increase in SPEP within 6 months of diagnosis or >25% increase in SPEP within the first 12 months of diagnosis. They didn't focus on light chains at all and I can't find any ...

Context for those answering the questions - the 2014 IMWG diagnostic criteria clearly list a K/L or an L/K ratio over 100 as a myeloma-defining event due to the high risk of progression to a CRAB event within 1-3 years without therapy. But, most of the data underpinning this criterion comes from a severely deranged K/L ratio at SMM diagnosis.

For patients where their SMM is a known entity and has been observed for at least 3 years without progression to CRAB, is a K/L ratio creeping up 40 —> 120 the same as someone with a ratio of 120 from the get-go?