Vincent Rajkumar, Professor of Medicine at the Mayo Clinic in Rochester and Editor‑in‑Chief at Blood Cancer Journal, shared a post on X about a recent article he and colleagues authored:
One of the main goals of our review article in NEJM on MGUS was to provide clear clarifications on the concept of ‘monoclonal gammopathy of clinical significance’ (MGCS). It’s all very confusing in the literature and can cause problems for patients if we are not totally clear about the concepts.
Read on to be 100% sure of the concepts so you can take care of your patients correctly!
- First key concept: MGUS is a clinically indolent condition that usually remains quiet for an entire lifetime.
The problem with MGUS is that it can progress to symptomatic malignancy (like multiple myeloma) or cause a variety of non-malignant, serious, and clinically important diseases that are collectively referred to as ‘monoclonal gammopathy of clinical significance’ (MGCS). - Second key concept: MGCS is like the title of a chapter in a textbook. It is NOT the name of a disease. Within the term ‘MGCS’ are several distinct diseases, each of which has its own diagnostic criteria, clinical manifestations, and treatment strategies. So you simply cannot diagnose ‘MGCS’ and treat, but need to identify the specific disease. All that the term MGCS does is to alert you that MGUS can cause serious non-malignant diseases besides progression to malignancy.
- The third key concept is: Some of the MGCS conditions are multi-system disorders like light chain amyloidosis and light chain deposition disease. Some MGCS disorders, on the other hand, are restricted to one organ, leading to more confusing terms like: ‘Monoclonal gammopathy of renal significance’ (MGRS), ‘Monoclonal gammopathy of dermatologic significance’ (MGDS), Monoclonal gammopathy of neurological significance’ (MGNS), and so on. These are also like titles of book chapters, NOT the names of a disease. Within each term are specific, unique diseases.
- The fourth key concept is: To take care of the patient, you need to know the name of the exact disease. Not just add an umbrella term like ‘MGCS’ or ‘MGRS‘. So, for example, instead of diagnosing ‘MGRS,’ you need to be clear exactly which kidney disease the monoclonal protein is accused of causing! MGUS is so common, and so many people can have MGUS and a completely unrelated kidney disease. MGUS plus kidney disease doesn’t mean ‘MGRS’. Most of the time, the two have nothing to do with each other. There are specific kidney diseases that are causally related to the monoclonal protein, and if we suspect MGRS for some reason, we need to work up and make the specific diagnosis, which needs a kidney biopsy: Proliferative glomerulonephritis with immunoglobulin deposits (PGNMID), C3 glomerulonephritis, and so on. Each of these disease have their unique clinical and lab manifestations, and treatment strategies.
- The fifth key concept is: With more and more sensitive tests for MGUS and more and more testing done for MGUS, we are all going to find M proteins associated with a variety of clinical problems, 99% of which are NOT caused by the M protein. I am hugely concerned with labels like MGCS and MGRS being wrongly applied. And the last thing we want is Dara-VRd for a DVT just because there is a paper that says M proteins can cause blood clots!
This Review will be a good place to start for getting all the key concepts straight.”
Title: Monoclonal Gammopathy of Undetermined Significance
Authors: S. Vincent Rajkumar, Shaji Kumar
Read the Full Article in The New England Journal of Medicine.
More posts featuring Vincent Rajkumar on OncoDaily.