MGUS Management Guidelines for Practicing Internists

Transcript: Simon Murray, MD: That is really interesting. As a practicing internist, if I stumble across a patient who has what I believe is MGUS [monoclonal gammopathy of unknown significance], do you believe I should refer that patient to an oncologist right away? Or do you think we’re competent to follow those patients along? And if so, how should we follow those patients? Is there, according to guidelines, a schedule for how we should follow them?

Ola Landgren, MD, PhD: Let’s start with the latter part of your questions. I think it’s important to say there are guidelines, as there are from most other things on the management. The guidelines come from experts such as myself and others and we meet on a regular basis and agreed to what would be reasonable to recommend to others. We see high volumes of patients. At Memorial Sloan Kettering Cancer Center, we had 10,000 visits last year. We have high volumes of patients with multiple myeloma. We have a lot of patients with monoclonal gammopathy. We do recommend the protein electrophoresis immunofixation and free light chains. And we also recommend to check the urine for baseline. If there is any indication of multiple things being wrong, it’s not a bad thing to refer that patient to a hematologist-oncologist or a specialized center, because there are some patients who actually could have what is referred to as the smoldering myeloma or even multiple myeloma category, that could be hidden in there. Even if the protein levels are not that high, sometimes you can actually see many more plasma cells. It’s relatively rare, but it could happen. There is nothing wrong having a second opinion. For a physician who is used to managing these patients, maybe he or she can just do all that work-up and follow the patient himself or herself. But I’m sure you and I have the same way of managing: we reach out and ask colleagues sometimes for advice. That’s important to keep in mind.

Simon Murray, MD: I myself probably would refer. I probably would feel that in the course of my world I would overlook things—you know, I might forget to check things. Because is it not true that once these things start to develop into multiple myeloma, you’d better catch them quickly or you’re going to get bigger problems?

Ola Landgren, MD, PhD: You’re absolutely right that there are some patients that can catch on and they can develop a lot of symptoms. We talked about the PLCO [Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial] from 2009, when we showed all myelomas were preceded by the monoclonal gammopathy. We did publish a follow-up study in 2019, where we went back to the same resource, with almost 100,000 people. And now we did a very careful characterization of the annual assessment for a range of serum protein markers in more than 200 patients who had developed myeloma. And we then had screened for 6000 individuals to identify the monoclonal gammopathy. There were around 400 cases with MGUS monoclonal gammopathy. And then we look year by year, what do these markers actually look like? We previously didn’t know which of these markers precede changes and how this really works. You can see that there are drops in the so-called uninvolved immunoglobulins. You have increases in the serum free light chains. And you could also have increases in the monoclonal proteins that could go on for up to 5 years before. In my clinical experience, there are patients who for no real reason end up in the emergency department because they have not been closely monitored and they end up with kidney failure.

Simon Murray, MD: Yeah, that’s very tragic.

Ola Landgren, MD, PhD: That’s very tragic. I see it every month where I work. We have patients coming from the tristate area, every month they are in the emergency department, they have kidney failure, and they end up having myeloma. They could have been caught earlier.

Transcript Edited for Clarity