MGUS shows up on a serum protein electrophoresis (PEL) as a spike. See figure. The spike is called an M spike.
It can be typed on immunofixation (IFE) to determine if it’s IgG or IgM or IgA; kappa or lambda. See below. 2/
MGUS was a term coined by Dr. Kyle.
He called It MGUS because prior to that it was called benign monoclonal gammopathy. Since he found a 1% per year risk of progression to myeloma he felt it the word “benign” may not capture the clinical implications adequately. 2/
MGUS is defined by M protein less than 3 gm per dl, and no myeloma defining events (MDE). A bone marrow if done should have less than 10% clonal plasma cells. (Not every patient with likely MGUS needs a marrow as I explain later; in fact most don’t). @TheLancetOncol 3/
MGUS was first estimated to be present in 3% of the population age 50+.
Prevalence is higher in men. And goes up with age. @NEJM 4/
When we add light chain MGUS (detected in serum free light chain assay) and use more sensitive mass spectrometry techniques the prevalence of MGUS is higher. Approximately 5% of the population age 50+
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The prevalence of MGUS is 2-3 times higher in first degree relatives of people with MGUS or myeloma.
But note myeloma incidence is only 4/100,000 per year. So 3 fold higher 12/100,000 is still a low risk. 6/
Prevalence of MGUS is also 2-3 fold higher in Black people. The higher prevalence of MGUS in Black people is the main reason for the higher prevalence of myeloma in this population
MGUS also occurs at an earlier age in Black people. @DrOlaLandgren led a lot of these studies. 7/
With mass spec a real MGUS is easy to detect and type. See below. 8/
But if one is not careful or experienced, you can start calling every little “spike” on mass spec a monoclonal protein. Then you end up calling half of the world as having MGUS.
(If we said BP >100 systolic is hypertension, then the prevalence of hypertension skyrockets).
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As an aside, lot of us would want to define a new disease for the first time
Dr. Kyle shows us how it’s done: He first set a specific disease definition; studied for years what the implications are with that disease definition; estimated the prevalence; made recommendations
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There are 3 major types of MGUS. Each has a progression phenotype that’s different. 11/
MGUS is associated with an approximately 1% risk of progression to myeloma or related disorder. @NEJM 12/
The progression risk persists indefinitely. But we are mortal and susceptible to lots of other diseases besides myeloma. So in reality the real risk of progression of MGUS to myeloma or related disorder over a lifetime is only 10%.
MGUS can be risk stratified using 3 simple factors: M spike >1.5 gm/dl, abnormal free light chain ratio, and non IgG type of MGUS are all risk factors.
If there are no risk factors, risk of progression over a whole lifetime is only 2%. Today that’s most of MGUS we diagnose! 14/
If an MGUS is suspected, not everyone needs a marrow or bone survey. Choosing wisely. The yield of these tests in low risk patients is close to zero.
You can omit marrow & bone imaging in uncomplicated patients with low risk MGUS, small IgM MGUS, light chain MGUS with ratio <8.
All patients with new diagnosis of MGUS should have a CBC, creat, calcium, protein electrophoresis and serum free light chain assay rechecked in 6 months. And if stable further follow up can be only at time of symptoms in low risk patients.
Yearly thereafter for all others. 16/
MGUS can be associated with several other disorders even without progression to myeloma or Waldenstroms Macroglobulinemia. This is often because the secreted monoclonal protein is an actual functioning antibody that is targeting something in the body. 17/
So clinicians should be aware of these associations.
A lot of associations are coincidental not causal. Knowing how to differentiate takes time and experience. No easy way out.
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Should we screen for MGUS? No, in general.
There are however specific populations that I feel a one time screening test is warranted at age 40+: Black people with one affected first degree relative with myeloma & all others with 2 or more first degree relatives with myeloma. 19/
To my followers who wonder what MOC is, and why many doctors are tweeting about it. Thread.
1) Maintenance of Certification (MOC) is a redundant requirement thrust on US physicians by a private organization. We resent it.
2) MOC is causing frustration and burnout. Over the years, ABIM certification and MOC have become entrenched and institutions and insurers require it and will not accept any other alternative.
I am advocating on behalf of my colleagues in the US for change. To end MOC.
3) MOC requires us to pay fees imposed on us by a private organization and take multiple choice question tests irrelevant to our practice.
10 suggested action items for physician colleagues suffering under the burden of @ABIMcert MOC. #MedTwitter
1. If your institution allows it, stop participating in MOC. Personally, MOC has no value to me.
2. If your institution requires ABIM certification, advocate for @InfoNbpas as alternative option.
3. Do not participate in more than one ABIM MOC specialty, the one that’s required by your institution. Save your money. Don’t spend a penny more than you have to.
I see a lot of wrong analysis on accelerated approval and surrogate endpoints.
It’s always easy to criticize from the outside. The criticisms raised are well known to the FDA and investigators. They are considered. We go in eyes fully open. We try to do what’s best for patients
Without accelerated approval using surrogate endpoint of overall response rate in single arm trials, for 2-3 years lives would have been lost waiting for drugs like Velcade, Revlimid, pomalidomide, Daratumumab, carfilzomib and more.
1) @costplusdrugs — where you can get >2000 prescription meds at lower price than almost any other pharmacy in America. Has revolutionized the generic prescription drug market. @mcuban costplusdrugs.com
2) @PayorDieFilm — the story of lives lost due to the high price of insulin in America. Likely contributed to why all 3 big insulin manufacturers have now cut the price of insulin by >70-80%. @scottaruderman @NSmithholt12
Watch on @paramountplus @mtvdocs
3) Inflation Reduction Act provisions to cap Medicare Part D copays.
For 2024, the out of pocket max for Part D drugs that a patient pays in copays is capped to a max of ~$3250. A huge relief to many.
Two days ago I did 60 ABIM MOC questions in Heme and Onc (against my will).
Almost all were esoteric/ irrelevant questions. Rare things that doctors rarely see. #MedTwitter
What’s my opinion?
1/
I spend a lot of time in medical teaching and writing. I write for UpToDate for 20 years, and all of the major Hem Onc textbooks.
In my opinion, the MOC questions are useless for routine Hem Onc clinical practice. Useless to assess “walking/ essential knowledge”.
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What’s worse: Every 3 or 4 questions that I spent time and answered, I would get a note that it was a “test question”. No answer was given at the end, making it a complete waste of time and making me an unwilling partner to test questions for the ABIM. @DavidSteensma
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