[0:09]What myeloma blood tests are useful if you suspect a myeloma diagnosis? Are urine tests ordered too? So when somebody presents with multiple myeloma, usually they present with some symptoms, whether that's kidney failure, high calcium levels, or bone lesions or fractures, you know, those are kind of the more common presentations. So we want to make sure that we are doing all the tests that's going to give us a sense of that organ function. So we definitely want patients to have a complete blood count panel, so a CBC. We want patients to have a comprehensive metabolic panel, which is going to look at their kidneys, the calcium levels, the electrolytes, etcetera. We want to check to see what kind of protein is present in the blood and the amount, and that test is called the serum protein electrophoresis, which is done on a blood sample that gives us the M protein concentration using that test. And then there's a test attached to that called an immunofixation, which then tells us the type. So it tells us the amount of abnormal protein in the blood, and then the type of abnormal protein in the blood. And now we're routinely sending what's a test called a free light chain, um, serum free light chain analysis, and what that is is basically looking at the light chains in the blood, kappa and lambda light chains. Uh, some patients just produce the light chain, so that's the way we detect about approximately 20% of myeloma patients that will actually have a negative serum protein electrophoresis, but very high serum free light chain. So that test is now used as an adjunct for us to diagnose most patients with multiple myeloma. And then in some cases, patients may have an M protein, but far greater light chains, for example. So you can have abnormalities in both those tests. So at the very least, you know, those are the tests that we want. Uh, we still do urine tests to detect, to see how much protein is being excreted into the urine, and then we can get a measurement of how many of these abnormal proteins are actually accumulating in the urine. That test is still done, uh, but I will say the light chain, uh, serum free light chain test has in a way replaced that now, because we are able to get most of the information now just using the blood. But we definitely, when we suspect myeloma, want to still get an initial urine test to get a sense of how much burden is present in the urine. What is the quantitative immunoglobulin test? So that at least in our lab comes as part of the SPEP test, but basically what that is is giving us the full measure of their immunoglobulin. So IgG, IgA, IgM, these are all proteins that we all have that are part of our immune system and our antibodies. Uh, so for example, if somebody that has an IgG kappa multiple myeloma, which is the most common uh, subtype, they may have very high level of IgG in the blood because, you know, they have their normal IgG and then the abnormal IgG which is accumulated. And then that quantification is what we do with the serum protein electrophoresis test, which tells us the breakdown of how much of that protein is actually abnormal. So they all are used to kind of give us essentially the same information but different ways of measuring it. In terms of the blood work that's helpful, so in terms of just first path looking for a multiple myeloma, the most common test is an SPEP, serum protein electrophoresis. What that is is to basically take all the proteins that someone has in their blood, and you basically run them across an electrical wire that allows you to see they all separate by how big they are and their electrical charge, positive or negative. And within the range of all the antibodies, you should see all the antibodies kind of very level. If you see one antibody that's way out of proportion, way too much of one particular antibody, that has made different names. It's called an M spike, an M protein, a paraprotein, a monoclonal protein, an abnormal protein. I was not there when they came up with these and I wish they chose a one name when they had, all the same thing, that can be a sign of multiple myeloma. Other blood tests that are helpful, so it's one of the criteria that separate true multiple myeloma with a cancer versus smoldering myeloma, the precancer, would be the presence of kidney issues or blood counts anemia.
[3:55]So I think, you know, checking kidney numbers, what's called a metabolic panel is important. I think checking your complete blood count or CBC is quite important. If uh, other tests that are helpful, um, even if someone doesn't otherwise would have smoldering myeloma, if their antibody ratio of kappa to lambda is way out of range, that can be considered myeloma defining. So to go back a step, uh, the test that I'm referring to now is called serum free light chains or free light chains, the name of the essay. The idea is that all antibodies, all immune, you know, infection fighting proteins come into flavors, kappa and lambda. The ratio should be about one to one, maybe two to one, maybe one to two. But if they check that test and the ratio is 80 to one or in this case if it's over 100 to one or less than one to 100, if the lambda is way bigger than the kappa or vice versa, that is considered myeloma defining. And I think that's important to know, not every patient with myeloma has an M spike, has a, has an abnormal M spike. So to recap, I would say myeloma wise, definitely the SPEP and the serum protein electrophoresis and the free light chains. I would say that looking for evidence of any symptoms or issues that would prompt treatment, looking at the blood counts, complete blood count CBC for the hemoglobin anemia, and looking at the comprehensive metabolic panel or basic metabolic panel, looking at the kidney numbers are important. And then there are other tests once they, if someone does have myeloma, we do some other blood work to kind of confirm the staging of it, and some other parameters, but I'm just suspecting it, I would focus on those. And again, depending on your doctor's suspicion, they definitely should do some form of head to toe imaging, and again, I think the one big takeaway where often our patients are the ones who are educating some of our community docs is that we don't do X-rays are not sufficient to to rule out multiple myeloma. If you are worried that you have multiple myeloma, your doctor should be getting some for a head to toe scan, either a cat scan, pet scan or an MRI. Is a 24 hour urine sample needed? actually one of my big research areas is what is the value of a 24-hour urine collection? So what I would say is two things. One, if your doctor is going down the testing of urine pathway, you should do either a 24-hour urine or no urine. A spot urine is obviously more convenient for patients but it doesn't, it's kind of the worst of both worlds. It doesn't give us all the information that we need and it might actually falsely reassure us. So just to recap what a 24-hour urine collection is. A 24-hour urine collection is basically really, most patients tell me it's more annoying than a bone marrow biopsy, right? That you take a jug of urine, often a brightly colored jug of urine, and for 24 hours we ask you to urinate in that jug, keep it in the fridge alongside your milk and your orange juice and bring it back. I'm saying that not to be cavalier, I'm saying that to say that it is a real issue for our patients, both logistically, and a lot of our patients have neuropathy or issues, difficult to actually physically collect a urine specimen. For patients who are driving a long dis or taking the subway into clinic is really weird to be carrying urine like that in a public space. So it's something that my research is actively trying to eliminate. It is part of our international myeloma working group criteria that were last updated a decade ago. My hope is that thanks to the work that myself and my colleagues are doing in the next iteration, 24-hour urines won't be part of that for most patients. If your doctor is doing it, I think it is helpful to look for the amount of myeloma protein that are in the urine there, something called Bence Jones proteins, which is another form of this M spike, the other where the abnormal protein. The one most important exception to everything I just said is that there are other types of plasma cell disorders that aren't necessarily multiple myeloma. One of them is called AL amyloidosis. When I talk about myeloma, I talk about it when I tell patients, it's kind of a myeloma is a quantitative issue, where just too many cells, too many proteins, causing anemia, causing kidney issues, causing so forth. Amyloid is amyloidosis is a qualitative issue, where even at low levels, the proteins, this light chains are forming clumps and they're actually depositing in the nerves, in the kidneys, in the hearts. If your doctor is at all suspecting amyloidosis in anywhere or form, or any form of kidney issues that are possibly related to a myeloma, pre-myeloma condition, a 24-hour urine is essential.
[8:13]And in that particular case, I do think it's very helpful for patients with amyloidosis, because in that particular scenario, there is a lot more protein in the urine than one would expect, and it's often albumin. It's often not the myeloma proteins, it's something else entirely. And the reason why for my patients with amyloid, I tell them that, hey, you may know that I research how to get rid of 24-hour urines, but not for you. Because for you, in amyloid, a 24-hour urine is often the first indicator that the amyloid is clearing out, meaning that for patients with amyloidosis, the 24-hour urine is very essential to chat them over time, because that starts to get better before the kidneys get better. Why are 24-hour urine tests becoming irrelevant? What are the better tools? So why why are 24-hour urine tests becoming irrelevant? So serum free light chains are available not just in the USA, but across the globe now. I think most countries have access to them and yes, so even for patients who have light chain only disease, for example, the serum free light chains are typically abnormal enough to catch it. Probably there's only one to 2% of patients where both the blood is negative and the serum free light chains are normal, but the urine is positive. I've seen it before, it is very rare. The idea is that for whatever reason that particular paraprotein, that a particular myeloma protein is only being expressed in the urine, is being cleared out of the blood through the kidneys into the urine, that is exceedingly rare. Um, for the vast majority of patients, serum free light chains are just a better indicator of what's going on. They are a better marker of remission than 24-hour urines and obviously much more convenient for the patient. So my hope is that as our, and there are future tests on the horizon. So even for patients who have quote unquote non-secretory disease where the blood is negative and the urine is negative, there are newer biomarkers, for example, soluble BCMA, soluble B cell maturation antigen that might actually be a better way to actually track the disease activity in those patients. So I hope, you know, five years from now is that we're not doing 24-hour urines anymore. My hope 20 years from now is that we're not even doing the SPEP or the light chains anymore, because we'll have a much better indicator of the myeloma cells themselves, and less some, so the protein that they're producing.
