What imaging should be done at diagnosis to detect myeloma bone disease?

Great question. And I love that you asked me that. We just have submitted a new guideline paper from the International Myeloma Working Group, and we recommend a low dose CT whole body low dose CT as a screening method because it shows the osteolytic lesions with the highest sensitivity, much better than the skeletal survey. If no CT is available, the skeletal survey is still the standard of care. But we recommend strongly to use a low dose CT because you have about 25% higher sensitivity to osteolytic lesions. So that's the screening. And if that's negative, then we can go further to magnetic resonance imaging, which also shows the changes in the bone marrow before there are osteolytic lesions. So we can kind of predict the osteolytic lesions and hopefully prevent them.

And also PET CT is very helpful because it gives, especially after treatment, information on residual disease. If we do a bone marrow biopsy of the pelvis, what we usually do because it's easy for us, at least for the patients, sometimes not that much. But it's easy to access the bone marrow. If we might miss something that is somewhere else, we see it lining up somewhere else in the body. So basically all of the above, but as a screening method at first diagnosis in basically every setting other than low dose MGUS, because I think those patients should be left alone. But every other patient should have a low dose CT whole body.

It's been known for many, many years that myeloma cells seem to stimulate normal bone cells, called osteoclasts, to break down bone. In a healthy individual, your bone is constantly being renewed by cells that destroy it and rebuild it to keep your bones healthy and strong; osteoclasts break down the bone and are followed by bone forming cells called osteoblasts. However, in myeloma, osteoclasts are stimulated to break down more than they should. Now, we don't really understand why this happens, but we know that this is again a very common feature.

And therefore years ago, the concept of doing what's called a bone survey. And that means basically taking X-rays of the skull, ribs, arm bones, leg bones, usually not the hands or feet would help in a search looking for bone loss or literally holes in the bone that can be seen with multiple myeloma. So many years ago, a bone survey, as it's called or skeletal survey, was incorporated as a part of a way to see if somebody had myeloma or not. So we still do that test and part of the reason, and I think sometimes this is very scary for patients, part of the reason we are interested in looking at the skull is because there is a very large expanse of bone that you can look at. And so if you are looking for holes, they're relatively easier to see in that situation. It doesn't mean that there is anything in the brain or anything like that. I think that's very scary for people sometimes to think about, but it's just a good place to look for those bone changes.

But most people believe that those bone surveys can be insensitive, that they can miss actual bone disease caused by myeloma. And more and more, we're doing what's called advanced imaging, and that means a test other than a bone survey or in addition to a bone survey to look for bone problems. Some of the most common ones that are used can be, for example, a magnetic resonance image or MRI of the pelvis and spine. And those are chosen because those contain actually a lot of marrow in the body. Between those two sites, you're talking about almost 80% of bone marrow in an adult. And so you do those tests looking for lytic lesions. That is the holes in the bone that can happen with myeloma. But you're also looking for changes in the bone marrow that might signal that a person meets the definition of myeloma I mentioned.

Nowadays we use that greater than 100 kappa lambda ratio to define myeloma. Also, that 60% plasma cells. And so along with that, if on an MRI, a person has more than one deposit that looks like myeloma on an MRI scan, we also would say that that person has myeloma with some of those other lab test findings. The other tests that can be done, there is a test called low dose whole body CAT scan or CT scan. This gives you a nice picture of the skeleton with a fairly low amount of radiation that is available in some centers, although not all centers. And then you can also consider doing a positive emission tomography scan that is called a PET scan. And what a PET scan measures are a couple of different things. One is metabolic activity in various places in the body, and typically in myeloma, you're looking for areas that have increased metabolic activity over normal, primarily in bones.

You're looking for asymmetry because that can certainly signal somebody has myeloma. That means that there aren't symmetrical changes in the bones one side to another. There is a CAT scan that's included in this. So you can look for actual lytic lesions as well. And then one feature that people like about PET scans is that if a person has what's called extramedullary myeloma, that is a deposit of myeloma outside of the bone, that kind of scan can pick it up. And there have been some studies looking at the utility of MRI and PET scans in people who are recently diagnosed with myeloma. And they are not perfectly accurate. They pick up abnormalities somewhere around 95% of the time. And these studies are offered more and more to patients to establish a diagnosis of myeloma. A PET scan also can be done after a certain treatment is delivered. And sometimes that's done to check up on how well that treatment is doing. And there are some studies that suggest improvement in a PET scan or normalization of a PET scan can be associated with better myeloma control.