Vincent Rajkumar, Professor of Medicine at the Mayo Clinic in Rochester, shared on X:
”I am worried about the exploding number of ‘monoclonal gammopathy of clinical significance’ entities. MGNS, MGRS, MGDS, MGTS etc.
It’s time to become strict with diagnosis of these disorders. MGUS is now more common because everyone is using very sensitive tests. Add to this some researchers saying you don’t even need a clone or M protein to diagnosis this. I disagree.
Even for the most well documented MGCS entity, PGNMID if there is no M protein, whatever you see on the renal biopsy is most likely driven by some oligoclonal process not monoclonal. So, no M protein, no MGCS/MGRS should be the default.
Over diagnosis and trying to eradicate the M protein is far more dangerous than under diagnosis. So you need a level of proof or compelling evidence that it’s the M protein that’s causing the problem. If that’s difficult to establish then it’s on us to get the testing right. Otherwise except for like established syndromes like POEMS, we need this rigor. Some entities like AL amyloidosis, cryo, PGNMID etc routine available testing gives the proof we need. Some others especially neuropathy and clots, are so common and so many causes, we simply need a very high bar for diagnosis. See our paper here.
For physicians who deal with lots of referrals on ‘abnormal free light chain ratio’ incidental finding.
Our recommendation is unless the FLC ratio is <0.125 or >8 or unless you are worried about myeloma clinically, or dealing with biopsy proven AL amyloid or MIDD or PGNMID, ask referring physicians to repeat in 6 months and if stable consider it as possible LC-MGUS with subsequent testing only if symptoms concerning for myeloma, amyloid etc develop. Defer bone marrow biopsy or bone survey.
Note labs report K/L ratio. Not involved /uninvolved. For ease of use you can calculate involved (high value) / uninvolved (low value). And use 8 as cut off as shown in figure. Otherwise you have to follow one cutoff for lambda and one for kappa.”
Title: Monoclonal Gammopathy of Thrombotic Significance
Authors: Matthew Ho, Saurabh Zanwar, Shaji Kumar, S. Vincent Rajkumar
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