Transcript: Simon Murray, MD: Do you think monitoring the free light chains [FLCs] is a valuable way to monitor people?
Ola Landgren, MD, PhD: Absolutely.
Simon Murray, MD: In hospitals or laboratories, do they have the capability of doing these assays? Or is there an assay that’s special, that’s different from others?
Ola Landgren, MD, PhD: The serum free light chain assays have been around for 15, 20 years. And these are the serum-based assays.
Simon Murray, MD: They were not urine based; they’re serum based.
Ola Landgren, MD, PhD: The serum free light chain assays have been around for 15 to 20 years. They are very easy to use. You take a regular serum tube, and you send it to lab. They can run kappa; they run lambda. There are multiple publications. We have published in something called the International Myeloma Working Group, many guidelines on how to interpret. It’s also in the NCCN [National Comprehensive Cancer Network] Guidelines. There are other assays out there, and you can use the urine tests also, but the urine tests are much harder to interpret, and the patient needs to bring 24-hour urine. Because the spot urine is not accurate for quantification. So the serum free light chain test is really what we use.
Simon Murray, MD: Are there any conditions that interfere with the accuracy of the FLC test, the assay? False positives and false negatives?
Ola Landgren, MD, PhD: There are a lot of factors to take into account. A person who has renal failure—for example, if the light chains go from the bone marrow, from the plasma cells into the blood, the blood goes through the kidney. If you have kidney failure, you end up having higher concentration. If you make light chains because of myeloma or monoclonal gammopathy and then you have a person who has a fluctuating kidney function, it will go up and down. It will to some degree artificially trick you as a physician, if you don’t know all these things, or what’s going on. You may think that it has worsened, but it is really a reflection of the renal failure. Also, another very important aspect is that these light chains are markers for immune activation. That’s something we looked into extensively many years back. In the most extreme cases, we look into HIV patients, but we also look for other types of conditions. And you can have very high levels of light chains in the setting of either an infection or inflammation or an immune condition. The person who has monoclonal gammopathy, who has a sore throat, these markers go up and the sore goes away; they go down again. These are practical considerations.
Simon Murray, MD: Yeah, HIV patients do have monoclonal gammopathies, I believe.
Ola Landgren, MD, PhD: They have the high levels of IgG, and they can also have M-spikes [monoclonal proteins]. If you treat HIV, the M-spikes can even go away.
Simon Murray, MD: How often are you seeing your patients in your clinic come back to follow up if they have MGUS [monoclonal gammopathy of unknown significance]? You’re watching them closely—how often do you have them come back?
Ola Landgren, MD, PhD: In these guidelines I was referring to before the International Myeloma Working Group, and the NCCN Guidelines, we have said that a person who has, as you mentioned, a high total protein, you should run protein electrophoresis immunofixation and serum free light chains. Also, I would recommend doing either a spot urine or a 24-hour urine for screening purposes. If you see that there are abnormalities, the skewing of the light chains, if it’s outside of ratio, and/or if there is an abnormal monoclonal protein, we would typically in these guidelines say repeat these labs within 6 months or so. If you see that they are still there, you should recommend a patient to be seen once a year. We have also said that if several of these factors that are abnormal—say, the protein is 2 g/dL, there is a skewed light chain ratio, the ratio is 20; maybe those suppression of the uninvolved immunoglobulins—then you should think about doing a bone marrow biopsy. You should also think about doing imaging, and I think there is another important aspect, so x-rays are totally out.
Simon Murray, MD: No more x-rays. We’re doing these CT [computed tomography] scans, PET [positron emission tomography] scans, etc.
Ola Landgren, MD, PhD: I’m on the NCCN Guidelines committee for myeloma. We took it out in 2019, and we said x-rays should be done only if you really have a good reason. And I cannot think of any really.
Simon Murray, MD: The bone scan. The bone survey.
Ola Landgren, MD, PhD: The bone surveys out are too old. It doesn’t work. It is very insensitive. Instead, if you do a PET or CT, which is 30 times more sensitive than an x-ray, you can rule out bone lesions. But also you can consider doing a whole-body MRI [magnetic resonance imaging] without contrast. Then you can actually capture changes in the bone marrow that the PET CT would not see and the x-ray would absolutely never see. So either do a PET CT, or you have only a low-dose CT or whole-body MRI without contrast.
Transcript Edited for Clarity