MGUS and Multiple Myeloma Diagnostic Criteria

Ola Landgren, MD, PhD: The diagnostic criteria for a monoclonal gammopathy of undetermined significance, or MGUS—whatever we like to call it—are as follows: you could have presence of a monoclonal protein that should be less than 3 g/dL. It should also be confirmed by a bone marrow biopsy showing less than 10% plasma cells by immunohistochemistry.

Simon Murray, MD: Is that necessary, the bone marrow biopsy?

Ola Landgren, MD, PhD: It’s not mandatory to say that the patient has to have monoclonal gammopathy, but you run the risk if you have the monoclonal protein and you didn’t check that the patient could have, say, 30% plasma cells. That would disqualify from the monoclonal gammopathy. That would roll into what the textbook refers to as a smoldering myeloma diagnosis, for whatever that’s worth. The monoclonal gammopathy says no more than 10%, or less than 10% of specifically plasma cells in the bone marrow and less than 3 g/dL of the monoclonal protein in the blood. Also, the light chains are part of it. If the serum-free light chain ratio is more than 100, that would also disqualify from monoclonal gammopathy because that’s part of the myeloma criteria. If you want to rule it out, you need to check the serum protein electrophoresis, immunofixation, and serum-free light chain, and do a bone marrow biopsy. You also need to run additional testing in the blood. You need to do CBC [complete blood count] and you need to do a comprehensive panel, because if the patient has anemia, that could make it multiple myeloma. And specifically, the hemoglobin if it’s 10 g/dL, or less or if it’s 2 units are lower than the lower level of normal at the lab, that by the book would make it myeloma, unless there’s another attribution to the anemia if you’re bleeding. Renal failure, you mentioned. If the creatinine is over the threshold or if the estimated glomerular filtration rate goes under 40 mL/min that would also be multiple myeloma. And then there is the comprehensive panel if you see evidence of hypercalcemia. Those are the blood-based tests and the imaging done to rule out the lytic lesions. And we used to have these so-called CRAB criteria.

Simon Murray, MD: CRAB criteria, yeah.

Ola Landgren, MD, PhD: Hypercalcemia for C, R for renal failure, A for anemia, and B for bone lesions

Simon Murray, MD: Yeah, I never liked the acronym.

Ola Landgren, MD, PhD: That is a little bit old school. No X-ray, but you should do a PET [positron emission tomography], a CT [computed tomography], or an MRI [magnetic resonance imaging] without contrast to rule out the bone lesions. And then the additional new criteria or variables in the new criteria from 2014 and onward is the light-chain ratio over 100 would make it myeloma, using the Binding Site assay, with that stipulated reference. Also, if you did an MRI on the whole body, if you were to pick up 2 or more focal aggregates in the marrow or in the bone, that’s going to also change it to myeloma. You can actually see in a small portion of patients who have what you think is monoclonal gammopathy that there are focal islands of cells, that have already started to aggregate. If you follow these patients, the majority of them will have myeloma within a year. Therefore, that is part of the criteria, if you have 2 or more of those. Lastly, if your plasma cell work-up from the bone marrow shows 60% or more by immunohistochemistry, that would also make it in myeloma. There are 7 variables, and some of these are quite clinical. I honestly do think in the coming future that there will probably be more genomic-based tests that will replace a lot of these old-school CRAB and all that. But we are not yet there. We are working on it.

Simon Murray, MD: Well, that’s been very helpful. That’s very helpful. Understanding things like the free-light assay has been helpful too. I will have to keep these things in mind.

Transcript edited for clarity.