What is Monoclonal Gammopathy of Clinical Significance (MGCS)?

What is monoclonal gammopathy of clinical significance?

Monoclonal gammopathy of clinical significance is another new umbrella term that we're using when patients have an abnormal protein and abnormal plasma cells in the bone marrow that don't meet criteria for multiple myeloma, like an m-spike greater than three or greater than 10% plasma cells in the bone marrow. However, the problem seems to be causing problems. And so we're starting to see that protein could cause neuropathy, or additional infections. And this is an area that's getting a little bit harder to determine.

In my own practice, a lot of times a patient comes to me with a symptom and they have a monoclonal gammopathy. What we try and do first is make sure that that problem that they're having, such as neuropathy, isn't caused by something else like a history of diabetes, thyroid disease, low B12 or vitamin D levels. And then once we determine that, we think that it's causing them a problem and that that's worth treating, then we go ahead and treat and see if their symptoms improve.

Is monoclonal gammopathy of clinical significance managed differently than MGUS?

So patients with monoclonal gammopathy of undetermined significance are monitored. And what we're trying to learn is who are those patients that we need to monitor more carefully and more frequently, because we think that their risk of developing a myeloma-related problem or enough myeloma to treat could be coming soon.

That was a big focus at our meeting, in Vienna, this past few days, in terms of what are some of the DNA changes in MGUS that make us more concerned about a patient and want to follow them closely. At the same time, there are patients with MGUS who are not going to progress. And we think that if they're stable and they have low risk factors, that that's something that will never cause them a problem in their lifetime.

It is when you have an m-protein that can cause organ damage, toxicity, even though it's not really myeloma. And there are different kinds of entities in this. This is the whole spectrum of diseases. And not all of them are treated at our department or at Department of Hematology. I like to think of it as we have an activation of the immune system. And when it's, it's, it's large enough, then you also present with an m-protein.

But diseases that we take care of are, for example, AL amyloidosis. And of course, also POEMS and neuropathy. It could be secondary to antibodies. But you also have cast nephropathy. You have a lot of glomerulonephritis. One thing that I learned from Melanie, who always said, dangerous small clones. And that's exactly what it is. You have a clone that produces an antibody that makes a mess, and they are extremely difficult to treat. And it's like being a detective when you want to catch them.

Because there's a lot of different kinds of diseases where you have and where the m-protein is associated with a certain disease.

What testing should be done if MGCS is suspected and what treatments should be done?

It is like this that it depends on what you suspect. Sometimes the patients I have referred to our department, if you suspect a plasmacytoma that can cause neuropathy, for example, I think you will be, you need to do a PET/CT. And you also need to do the normal workup with bone marrow and blood samples. You need the biopsy from a plasmacytoma if that's the case. If you go to another entity like amyloidosis, it requires a collaboration with colleagues from all over the hospital.

Because this MRI can be depositing in every organ, and you need the standard workup for myeloma, but you may also need to make a biopsy from the heart and from the kidneys. From nerves, maybe. And you need to take certain kinds of blood tests, like vascular endothelial growth factors and, when you have a disease that is related to cytokines like this, then there are diseases that affect bones and you have to go to all organs in the body to make an assessment of these patients.

Careful, careful, careful examination. And then the treatment when you are dealing with these small clones, you still need to have an effective treatment, like, if you have amyloidosis and you are, well off in that sense that you don't have any comorbidities according to the Mayo criteria, you can go directly to harvest of stem cells and then a transplant. I mean, in these days, you can even use the antibodies against CD38 for treatment.

Then there are entities like where you find an antibody produced by a precursor of myeloma cells and you can treat it. I think it's called rituxan in the US. And so there are things that you can do, but some of it is really, really difficult to treat. I think if you have amyloidosis and you can go to a transplant, then you are actually well treated.