What testing should be done at relapse? What is restaging?

What testing should be done at relapse? What is restaging staging?

Myeloma is a complicated disease. Many other cancers’ restaging evaluation consists of a scan, and that's it, and that's done every four months.

Myeloma is unique in that we do restaging testing when somebody is on treatment every month and when somebody is off treatment about every three months. At relapse, a full restaging includes blood testing. That blood test is a CBC, a chemistry, an SPEP which includes your M spike, a serum immunofixation, your free serum light chains (that's your kappa and lambda), and quantitative immunoglobulins.

Then, a 24-hour urine test is done, which is a collection of urine over a 24-hour period. That looks for how much protein is being excreted through the kidneys, and not only how much protein, but what type of protein — is it myeloma protein or nonspecific protein? The reason it's important to do that urine test is because we want to know, A) if the myeloma is affecting the kidney, and B) if our treatment is causing harm to your kidney. In particular, Zometa, which is given very often, can cause harm to the kidney and increase protein secretion through the kidneys.

Other restaging tests include bone imaging, PET-CT, or MRI. Sometimes we do an MRI of the bone marrow. It's a very good test because it's very sensitive; it shows almost all lesions even before they break through the bone. The problem is, if you've never had it in the beginning, it's hard to tell with that test what's old and what's new. That's why a PET-CT is very useful because it will show us any active lesions or a lesion that's new. The last thing I do for a full restaging is a bone marrow test.

I think it's important to restage completely from really head to toe with each relapse because the disease can really change in terms of what end organ symptoms are affected, and also in terms of the biology or the genetic testing of the disease. The first thing you want to think about with each relapse is how did the symptoms start in the first place? What were the initial presentation symptoms? So, if somebody had a fracture when they were first diagnosed, you need to do a bone image, a PET-CT, or an MRI.

If somebody had anemia when they were first diagnosed, you may want to do a full anemia workup. If somebody had frequent infections and they're now showing more frequent infections or fatigue consistent with their symptoms that they initially had, it's worth considering that this is a relapse, even if the numbers don't show it. In addition, even if somebody didn't have bone disease in the very beginning, it is a good idea to do some kind of bone imaging at a relapse because you want to know if new bone lesions developed. About 10% of the time, even higher in some instances, you can have a bone event — lytic lesion, a fracture, or a soft tissue tumor of the bone at a relapse.

A good idea is to do a PET-CT or an MRI at relapse. I also like to do a bone marrow evaluation because you want to know how much myeloma is involved. We now have much more sophisticated testing than we did a few years ago, and every year we improve our ability to test the genes of the cancer. We are detecting some genes that may even have treatment options. So it's important to do a FISH test on the bone marrow and a next-generation sequencing test. Those are the two genetic tests that can give us new information about the myeloma: How is it changing, and are there any treatment options that are personalized for your type of myeloma?

When a patient has a relapse, we hopefully pick that up with blood work alone, as opposed to them getting ill. That's why we watch people carefully who have multiple myeloma. We want to see the myeloma proteins rising well before a person doesn't feel well. When a person does have a recurrence, there's a discussion between doctor and patient and their family about what adjustments should be made in the medicines to get the disease back under control, depending on the nature of the recurrence.

How fast did the person start to feel ill? For example, do they have new bone pain? Certain testing may need to be repeated. Body imaging — PET scan, CAT scan, MRIs — might be done if there are certain symptoms attributable to potential bone disease. Sometimes we do a new bone marrow biopsy looking for evolving genetic changes in the bone marrow. However, this is not always required before starting on a new therapy. These decisions are really individualized based on the nature of the patient, their disease, and where they are within the course of illness.

Yeah, so I think, you know, that's a great question. Again, we're very lucky with multiple myeloma because we have a natural biomarker of disease. That natural biomarker is the M spike or, in some cases, a serum free light chain ratio. What I mean by that is it gives us a way to monitor this disease without actually looking at the disease or looking at those cancerous myeloma cells, based on just a blood test, which is great. In a lot of diseases, unfortunately, you don't have that, but it's very similar to how patients may be monitored with PSA in prostate cancer.

However, it's important to know that at the end of the day, you're looking at a surrogate marker almost — you're not looking at the actual cancer cells when you look at an M protein or serum free light chains. I think that in many cases it is important, if it seems like the patient is relapsing based on the blood markers, to confirm relapse. There are a lot of reasons to do restaging.

Some reasons could be to see the extent to which the myeloma has come back, to see if it has changed at all, to see if the FISH results are the same or not, because that could even impact treatment down the road. Also, I definitely like restaging with PET-CT for sure, because, number one, it's not as invasive. So, if a patient is not too keen about getting another bone marrow biopsy, I at least try to get the PET-CT because they also say the extent of disease you're dealing with. And I think that's really important as you start a new therapy because, if they relapse, presumably you're going to start what's called a second line of therapy.

And you really need to know where you started from so that down the road, you know where you got, especially if there's any questions.