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The Fellow on Call: The Heme/Onc Podcast
Episode 141: Myeloma Series, Pt.2 - Intro to MGUS and Smoldering Myeloma (2025)
Ronak Mistry, Vivek Patel, Dan Hausrath
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A
Hey, friends. This episode of the Fellow on Call is not meant to be used for medical advice and is intended for educational purposes only. Patient information has been modified to ensure privacy. The views expressed in this episode do not necessarily reflect the views of our employers.
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B
Enjoy.
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A
Welcome to another episode of the Fellow on Call, the hemong podcast. We're coming at you from Rula University Medical Center. I'm Ronuk.
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B
I'm Vivek.
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C
And I'm Dan.
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A
And in today's episode, we continue our discussion on our myeloma series. This time we take a deeper dive into MGUs surveillance, defining smoldering myeloma and talking a little bit more about the diagnosis of multiple myeloma.
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B
Yeah, this is going to be a very critical episode in the field of multiple myeloma for everybody to understand. We really go through the things that I truly didn't understand, even after about two and a half years of fellowship. So this is a great episode. We spent a lot of time on it, excited for you guys to listen.
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A
So let's go ahead and roll that show.
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As you know, we have started our discussion about the spectrum of plasma cell dyscrasia and we're slowly inching our way towards that, that discussion about multiple myeloma. But I have a case that I wanted to run by you all in light of the discussion that we had last time to just kind of continue that conversation. So if you're ready, I have it for you.
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C
Yeah, go for it.
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A
So this is a patient that actually was in my clinic not too long ago, and I think that she serves as a great illustration for this discussion. So she's a 63 year old female with a past medical history of hypertension, hyperlipidemia and diabetes who developed worsening normocytic anemia with a hemoglobin of 8.9. Previously, she was kind of in the 11 and a half range and her nutritional workup and colonoscopy were unremarkable. Her primary care physician had ordered an SPEP with an immunofixation which showed an IgG Kappa M spike of 1.2. And so in light of this M spike elevation, she was referred over to see me in my hematology clinic. Listeners, you'll recall from our last episode that if you order the spep, you always want to order those free light chains with it. And remember, that's to help US stratify the MGUs and determine if we need to do additional workup like get a bone marrow biopsy or get some sort of full body imaging to rule out those lytic lesions because remember, that would change our management in approach to this patient. So I went ahead and ordered some free light chain ratios as you guys taught me to do. And it showed a kappa light chain of 2.7 milligrams per deciliter, a Lambda light chain of 1.7 milligrams per Deciliter, and that results in a ratio of 1.5:9. So in light of this information, where do we go from here?
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C
Well, let's start by going back over how the SPEP and light chains can inform our decision here. Remember that the SPEP itself is a quantitative test. You use it to identify exactly how much of this monoclonal protein is in circulation. The two biggest categories of serum proteins are going to be albumin and then the globulins. So the SPEP reads out sort of a quantification of the amount of albumin and the amount of other globulins, which divide into a series of different peaks based on their size. Alpha 1, Alpha 2 and Gamma. An M spike is an abnormal concentration or an abnormal protein that is monoclonal. That's what the M stands for. And it forms a large peak or a spike on that protein. Electrophoresis readout. It's in the immunoglobulin region, so it runs in the gamma region. And based on the area underneath that spike, you can tell exactly how much of this abnormal protein is around. You'd still need immunofixation to help you identify exactly what that M spike consists of. Is it an iga, an igg, et cetera? And it'll also tell you what type of light chain is associated with that admiral protein. Is it all kappa or all lambda? The type of monoclonal protein that is, what class of immunoglobulin it is, and the quantity of the M spike both help us risk stratify patients and prognosticate. The light chain ratio is also key in helping us risk stratify.
- [04:20]
B
Dan, that was great. And the other thing I wanted to mention, other than getting these serum free light chains along with that spep, is that you'll see oftentimes that the hematology provider will order a 24 hour upep. I want to note that this is very critical in determining how to risk stratify these MGUs patients. And as we'll talk about in a little bit, how to define a patient who might have something like a smoldering multiple myeloma. So remember, don't get a spot upep that is not clinically. Useful. Always get a 24 hour u pep and that'll also give us a 24 hour protein quantification. Those are critical in helping identify these patients that are high risk for myeloma or that have something called smoldering myeloma.
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A
Thanks for those reminders, guys, that's really helpful. And you know, the other thing that I recall from our discussion last time was also that to make a true diagnosis of multiple myeloma, so the other end of the plasma cell dyscrasia spectrum, we require a tissue biopsy, that is a bone marrow biopsy, in addition to meeting these clinical and lab features. So could we talk a little bit about how we risk stratify patients and decide when we do additional imaging or get a bone marrow biopsy? Like for instance in our patient who has an m spike of 1.2 and has a free light chain ratio of 1.59 and the fact that she has an IGG Kappa predomina. When do you consider doing any additional testing for her?
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C
That's a really good question. So already off the bat, just from seeing that she has an M spike, we know that there's something going on with her plasma cells. There's some clonal population of plasma cells, but we also know because that quantity is less than 3, there's a good chance she's going to end up having mgus or monoclonal gammopathy of undetermined significance. That's defined by an M spike of less than 3 and fewer than 10% of bone marrow plasma cells without any myeloma defining clinical events. But you asked about high risk features and that's a really good thing to remember because there are going to be a lot of mgus patients that you'll see out there, and it's important to know which ones are going to require additional testing. So those high risk features that tend to warrant more workup are anybody that has a non igg type of M protein, anyone who has an M spike greater than 1.5 or an abnormal free light chain ratio greater than 1.65 or less than 0.26. Basically because the ratio is always kappa over lambda, it can be either really high or really low. When somebody is higher risk, if any of these high risk features is present, you want to go ahead and get the bone marrow biopsy and PET CT or MRI to look for those lytic lesions and other findings that might point you more towards the direction of a smoldering myeloma or just a higher risk MGUs.
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A
That makes a lot of sense. And so just to recap, again, Dan, you said a non IgG type, an M spike of greater than 1.5 and a free light chain ratio that's abnormal. And abnormality is defined as a kappa lambda ratio greater than 1.65 or less than 0.26, correct?
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C
You got it.
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B
And going along the lines of that, I want to talk about a few things. One is what exactly are we talking about when we talk about kappa light chains and lambda light chains in terms of our interpretation in the serum? And the second thing I want to talk about is where did this idea of risk stratifying the MGUs come from? And why do we worry about MGUs? What does it mean? So I'll start with the first thing. So let's talk about light chains. The key thing to know here is that, remember, as we talked about in the previous episode, we have the Y shaped structure of an immunoglobulin and it's composed of two heavy chains which form the base of the structure and two light chains which kind of hang off the edge. If you were to look at a diagram, and we'll link that in our show notes, what your body does is it actually produces an excess amount of light chains when compared to the heavy chains. So as a result of that, in your normal body, you will have excess light chains that you need to excrete, which is done primarily through the kidney. The interesting thing about this is that your body in general produces more Kappa than lambda in a normal situation. So your body, your plasma cells, even though they choose kappa or lambda that we talked about, in general there's more kappa than lambda because this is renally cleared. What ends up happening is that lambda, unlike kappa, forms dimers and has a higher molecular weight than, which decreases its total renal clearance compared to kappa. So even though you're producing more kappa than lambda, you're not clearing lambda as quickly in a normal patient. And that's why in normal scenarios, often the kappa lambda ratio is less than 1. And that's why you have that normal range of 0.26 to 1.65, because it's often less than 1. And that's normal for the reason I just said. The important thing to know is to how to interpret this in a person who has kidney dysfunction. So if you were to send light chains and somebody who has renal dysfunction, whether that's an AKI or developing worsening renal failure, what you'll see is that this idea changes a little bit. Instead of these light chains being cleared by the Kidney, your reticulo endothelial system kicks in to clear the light chains. That system isn't dependent upon molecular weight, so those dimers that the lambda light chain forms doesn't affect the clearance mechanism. And remember, you produce more kappa than lambda. But now you don't have to worry about lambda being cleared slower than kappa. So you'll ultimately have a kappa predominant situation, particularly in patients with renal dysfunction or aki. And when we looked at this in studies, looked at patients with dialysis, what we found was that patients can have kappa light chains up to 13 milligrams per deciliter in a normal ratio. Range is elevated a little bit. It actually goes up to 3.1 being normal. So what I'm trying to say is in renal dysfunction, remember that kappa is higher than lambda and the normal ratio goes all the way up to 3.1.
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C
That is so important. I've gotten a ton of referrals and consults just about this patient with renal dysfunction and an abnormal free light chain ratio. And I mean, first thing your mind's going to jump to is, oh, geez, well, myeloma can cause kidney dysfunction. Are we in trouble here? But then, like you said, you see that fairly reassuring low level elevation of light chains, you see that ratio that reflects more closely the ratio in which kappa and lambda are produced in the body. And you can tell yourself, okay, this is probably just a consequence of renal dysfunction and not causative of it.
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B
And the second thing I wanted to talk about was this whole risk stratification and how we got to there. And the big thing is most of the studies in multiple myeloma that you'll find have been done from Mayo Clinic in America. They have a rich set of patients and data, and they've done a really good job analyzing that data. So one of the important studies was a retrospective study of 1384 patients seen at Mayo Clinic. And they looked at what is the risk of progression to multiple myeloma at 20 years for patients with MGUS? Well, what they found was that if you had all three of those risk factors present that Ronick and Dan talked to you about, at 20 years, your risk of progression to myeloma was 58%. If only one of those risk factors was present, it was 21%. And if none of those risk factors were present, so you had a very low risk MGUs, the risk of developing myeloma was only 2%. So what this means is, well, if I have a really low risk of getting Multiple myeloma, only 2% risk over 20 years doing a bone marrow evaluation and imaging studies looking for lytic lesions is not cost effective and will lead to unnecessary testing. And that's why it's critical to use those risk factors to stratify these patients.
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A
That makes a lot of sense, and it's really helpful because now I think I have a framework of how I counsel a patient. Right. It's scary for them to come to see a hematologist knowing that there's some abnormality in their blood and they hear things about multiple myeloma. And it's so reassuring because you can, you can put a number to it. Right. 2% progression is pretty low, and it gives you some backing for when you have a frank conversation with your patient. But you know, to that point though, because there is still a risk of progression, how closely do we monitor these patients and how often do we repeat these labs?
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C
Great question. After you figure out that somebody has one of these M proteins in circulation, all comers will need repeat labs at the six month time point. If all their lab markers remain in the low risk range, like our patient, there's no need to necessarily repeat serologic testing down the road. Unless new symptoms are coming up like bone pain, new hypercalcemia, unexplained anemia, weight loss, any of those big red flag signs that tell you something might be changing. If the patient has mgus but is not in that low risk category, then you want to get repeat labs annually. And that includes a cbc, a measure of their kidney function with creatinine, a calcium level, repeat spep, and a repeat free light chain.
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B
Yeah, and that's critical because remember that these patients who did not have low risk MGUs, they had a bone marrow biopsy that was done. Right? They had their bone marrow biopsy, they had their imaging studies that were already done, and they definitely had less than 10% plasma cells in their bone marrow. So that's the patient that we're talking about. And they also had a 24 hour U Pep done. And we'll talk in a second about how we define smoldering myeloma. But we're talking about these patients who don't have smoldering myeloma. They just had MGUs. And the key thing that Dan was saying is that we check it six months and then annually thereafter is a pretty reasonable Strategy. Why the 6 month check for everybody? The reason is there's been several observational studies that have shown for patients that are progressing from either MGUs or smoldering myeloma to overt Multiple myeloma, that's more likely to occur in the first year. So the first year is a critical time point. And then after that, between years two and five, the risk decreases. And then after year five, there's a significant decrease in the risk of transformation to overt multiple myeloma.
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A
I see. And so to follow up with that question, though, we talked a little bit about additional imaging and bone marrow biopsies not being necessary for patients that are deemed low risk at the time of diagnosis. But when do you consider doing any of those studies?
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C
Afterwards, whenever you have a patient on a monitoring track, this is an important thing to think about. What are you looking for? What are you trying to find that's going to trigger you to do something? So even if a patient has progressive rise in their M spike over three consecutive measurements, only about half of those will develop multiple myeloma overt multiple myeloma at 10 years. So even then it's not quite definitely. What we found is the biggest predictor for progression to overt multiple myeloma is an M spike that rises by 0.5 in absolute value of 0.5 and a decreasing hemoglobin of 0.5 over a year over the course of a year. So if you are seeing a more rapid rise in your patient's M spike in coordination with a decreasing hemoglobin, those are the patients where I would be a little bit more concerned and I'd want to talk with them about reassessing their disease with either marrow or with more imaging studies.
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B
And obviously, if these patients develop symptoms that are concerning, you're going to repeat those studies. So you're just watching these patients closely. And remember that if it's that low risk MGUs, these patients don't need testing after that six month mark. Everything else you're doing at least about annual testing and you're monitoring their symptoms and keeping a close eye on them.
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A
Okay. Okay. So I feel like I have a pretty good grasp of MGUs and. But you know, again, for the purposes of advancing this conversation, why don't I change the case just a little bit? And let's say our patient, our 63 year old female, had igg kappa M spike, but this time it was 2.2 and a kappa light chain of 70, a lambda light chain of 7. And so then the ratio is actually 10 and otherwise, though unremarkable hemoglobin, calcium and creatinine. So essentially this patient has an m spike of 2.2 that's IGG Kappa predominant and has an Elevated kappa lambda ratio to 10. How would we go about working this patient up and how is this different?
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B
So this gets to the point when we talk about why did we get that 24 hour urine study and what is the difference between MGUS and smoldering myeloma? So smoldering multiple myeloma is defined by two criteria. Criteria number one is either of the an M protein greater than 3 or 500 milligrams of monoclonal protein collected over 24 hours, hence the 24 hour UPEP, or clonal plasma cells in the bone marrow between 10 to 60%. The second criteria is that we don't have any myeloma defining events. And I'll let Dan talk about some of those myeloma defining events here in just a second.
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A
I see. So the difference being in this case, Vivek, based on what you just said, in terms of diagnostic criteria, given the higher M spike and the higher ratio, this patient, we would have done a bone marrow biopsy on, we would have got the PET CT on to look for lytic lesions. And so essentially you're trying to do all the work up to ensure that they do or do not fit any of these diagnostic criteria for smoldering myeloma.
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B
Yep, that's exactly right. And the interesting thing is you could have a patient who has a 24 hour U PEP with greater than 500 milligrams of monoclonal protein collected over 24 hours. And that's a synonym for the benzion protein that you would learn about in medical school. And that patient doesn't need an M spike greater than three, and it doesn't need necessarily a high bone marrow plasma cell percentage of 10 to 60%. And that patient could still be defined as having smoldering multiple myeloma. So you can see how that 24 hour UPAP is essential. The second thing with that 24 hour UPAP that I wanted to mention right now is that we also use that to monitor for treatment response. So that baseline disease status is key. So always remember, don't get a spot, get a 24 hour.
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A
Don't get a spot, get a 24 hour.
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B
Got it.
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A
And you used a particular term, myeloma defining events. Can we. I feel like we use that term a few times now. I think it's probably time that we define that for our listener.
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C
Yeah. So back in the ancient days, when I was a med student eight years ago, we used to go by the CRAB criteria as myeloma defining events. Now, these are clinical criteria that demonstrate end organ Damage related to the expansion of a plasma cell clone. This classic CRAB criteria was hypercalcemia, renal insufficiency, anemia, and bone disease. That's what we always learned in our heme block and heard it a thousand times on the wards. But these days, we've added on to that a little bit. There's been an update adding these slim criteria to the crab criteria. The slim criteria were found to portend a very high risk of progression to overt myeloma, about 80% at two years, which is why we're now considering it sort of morally equivalent to overt myeloma. We consider it myeloma defining if some of these slim criteria are present. The idea being that we can have an opportunity to treat these patients with myeloma treatment before they develop the end organ damage that's evident in the crab criteria. So let's go through all of these. The S in slim is for 60% or greater clonal plasma cells in the bone marrow. The S for 60. The Li in Slim is for a light chain ratio greater than 100 or less than 0.1, basically a hundredfold difference between involved and uninvolved light chains. The M is for greater than 1 focal lesion greater than 5 millimeters in size on MRI. So the M for MRI showing greater than 1 focal lesion, and then the crab hypercalcemia, defined by greater than 11 milligrams per deciliter calcium. The renal insufficiency, a creatinine clearance of less than 40, serum creatinine over 2, anemia to less than 10 or 2 grams per deciliter below normal for that patient. And bone disease on conventional radiography, one or more lytic lesions seen on ct, PET CT or plain radiograph. It is important to keep the patient's overall health as a context in mind, because if you have a patient who's anemic because they were on dialysis for years and their renal function is bad because of diabetes, completely independent of any plasma cell dyscrasia, It's a little bit difficult to say that, okay, now this person has a myeloma defining event because they have bad renal function and an M spike. You're really looking for things that you can't otherwise explain away by other features of that patient's health or things that have developed in a suspiciously close correlation in time with a progression or development of an M spike. So those are what we consider myeloma defining events, Slim crab. And again, these will be all listed in our show notes. But when we say Myeloma defining event. That's what we're talking about.
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B
Yeah, Dan, one of the things I wanted to piggyback off of that was this whole idea of the slim criteria coming up, and that's that, like you said, high risk of progression to multiple myeloma. These were the ultra high risk smoldering multiple myeloma patients. Essentially, these are the patients that would inevitably get multiple myeloma. And one interesting thing about the light chain ratio, because it's interesting, right, if you have involved minus uninvolved of 100 or greater, we consider that a myeloma defining event. Well, the group from Mayo Clinic did a study where they said, well, what if we also looked at the urine monoclonal protein over 24 hours, again reiterating the concept of why a 24 hour UPEP is important. And what they found was that a cutoff of 200, meaning that if you had this light chain difference of 100, you also had to have a urine monoclonal protein greater than 200mg over 24 hours to really be defined as a myeloma defining event. So it's critical to use both of those values. I know it's not an easy mnemonic to remember, but just note that there's a modifier with that 24 hour UPEP.
- [23:15]
A
So, as we said, our patient did not have any myeloma defining events based on the slim crap criteria that Dan just outlined, but did have smoldering myeloma, given the fact that when we did her bone marrow biopsy, she had 20% plasma cells, so that's greater than that 10% plasma cell cutoff. And she also had 600 milligrams in 24 hours of a urine monoclonal protein, which is greater than that 500 threshold that we talked about. I suspect that similar to how we risk stratified patients with MGUs. And something similar probably exists for smoldering myeloma as well, if I'm not mistaken.
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B
Yeah, Renuk, that's absolutely right. And this is another study that in the lung cancer series, we said, this is a study every fellow should know. And we're doing that again. So every fellow should know. This study, and it was done by Kyle et al in the New England Journal of medicine published in 2007. This was coming out of that Mayo group and what they did was they did, it was a retrospective study for Mayo Clinic that looked at patients who met the smoldering myeloma criteria. And they said, what is their risk of progression to overt Myeloma, what they found was at 20 years, the risk of progression to myeloma was 80%. So that's pretty high. And when you compare that historically to MGUs at 20 years, the risk of developing MGUs is about 20%, 1% per year that you heard us talk about in the episode last week. So we're talking about 80% versus 20% when you have smoldering multiple myeloma. So it's a different ballgame that has a different monitoring strategy. And that also gets to another important point that Ronick was talking about, about the risk stratification. Smoldering multiple myeloma. The definition of it, the idea of it will probably change by the time this episode is released. It's constantly changing. It's an incredibly heterogeneous entity and it's very controversial. And, and how to split these patients up. And really, this is why we shouldn't really call this whole disease entity multiple myeloma. But the multiple myelomas, you know, it's so complicated. But the idea here is that smoldering myeloma has a progression of risk that decreases over time, like mgus was. And really what you're looking at in the first five years is about a 10% per year risk of progression. But then that decreases over time. Why is that? Well, some patients with smoldering myeloma are really towards the pre malignant spectrum that maybe they didn't develop overt myeloma in those first five years and it's decreasing over time. So maybe they won't. They're always going to stay premalignant. And that can swing this spectrum, can swing all the way to the patients who develop myeloma within one year. And those patients are more towards that. Maybe they already had a malignancy spectrum. And this is actually how the slim criteria came about. It was that ultra high risk group of smoldering myeloma patients that we said, you know, this is morally equivalent, this is a myeloma defining event. And so that's really what happened. And that's really an important concept to understand that smoldering myeloma is a spectrum. There's going to be some patients who are in the more pre malignant phase and there's going to be some patients that are more towards the close to overt malignancy. And we can differentiate these patients, which helps us figure out how to monitor them and consider ideas of should we treat them. So that's the key thing. But Dan, can you tell us a little bit about how we risk stratify these patients and some scores that were developed, sure, there have been a few.
- [26:43]
C
Different scores out there created by some groups in Spain and Mayo Clinic and Big Myeloma Center. And for simplicity's sake, let's focus on the Mayo criteria from back in 2018. The numbers to remember are 22 and 20, and that's 22 and 20, not 22. The free light chain ratio of greater than 20, an M spike greater than 2, and a bone marrow plasma cell percentage greater than 20. If two or more of these criteria are present, then you're in the high risk category. These criteria can actually even be used to qualify patients for enrollment in trials, looking at whether or not it makes sense to treat them as though they have myeloma. So really important criteria, remember, that's a greater than 20 fold difference between the involved and unfall free light chain, an M spike greater than 2, or a bone marrow plasma cell percentage greater than 20.
- [27:39]
B
And the key thing to know is that these risk factors, two or more of those puts you in the high risk, smoldering myeloma camp. And for those patients, we know that their risk of progression to overt myeloma is about 50% within the first two years. So that's 25% per year. And that's why when we talk about, in the next episode, when we talk about treatment, you'll see that there's been some work to figure out should we treat these patients early.
- [28:08]
A
So the 2220 rule. And so if you meet two of those criteria considered high risk, so then by default, I guess that means if you meet only one of those criteria, you're low risk. And I actually had this discussion with one of the attendings about these patients with smoldering. And I'm going to give it a shot and see if I can remember the work up here. So it was recommended that we monitor labs every three to four months in these low risk patients for the first five years, because we know that's the highest time at which there's a risk for progression. And then once you get beyond that five year mark, you space it out to every six months thereafter. And recall that if a patient progresses to high risk based on the 20 to 20 concept, that you want to watch them even closer because you're worried about them developing an overt malignancy. And this further highlights just how heterogeneous the spectrum of disease of the myeloma, as Vivek put before, really is.
- [29:13]
This is a rapidly evolving field. There's a lot of information that's Coming out, you need to be paying close attention to those data that are coming back on our patients and reassessing every single time you meet the patient as to how their disease status is doing?
- [29:28]
C
You nailed it. Like you said, each time we measure a patient's disease, that's just a single moment in time. And so having an idea of their trajectory is critically important. And you're absolutely right. If a patient does progress to being high risk, when you're monitoring them closely, you found disease that's on the move and you need to keep an even closer eye.
- [29:48]
A
So ultimately, in this case, we, in a shared decision making approach to our patient's care, decided that we were just going to closely observe her. And as we also pointed out though, there is still a lot of gray when it comes to treatment in this field. So, Vivek, I was, I was curious though, you know, are there other risk factors that you ever consider that are not truly encompassed in the 20 to 20 rule that we should just kind of be keeping in the back of our minds when we are doing these frequent reevaluations in our patients?
- [30:22]
B
Yeah, definitely. And there's a couple of key concepts that we really want to highlight. Key concept number one, we mentioned it earlier. If there's an increase in the m spike by 0.5 and concurrently a hemoglobin decrease by 0.5 points within a 12 month period, this portends roughly a 90% risk of progression to myeloma. So that's a very high risk situation. So M spike goes up by 0.5, hemoglobin goes down by 0.5 points. That is something that we worry about. And those patients have a high risk of developing myeloma. And that was confirmed by two studies, one done in the United States and another done in the Spanish group. And we're going to link those to our show notes very clearly, especially if you guys are interested in looking at it again. I think I learned so much preparing for this episode by looking at some of these studies. Another thing that we found as a risk factor is decreasing uninvolved quantitative immunoglobulin. So I always thought, why are we getting quantitative immunoglobulin levels like IgG, IgA and IgM? If we know we have an Igg kappa M spike, for example, the reason is as the other immunoglobulin levels go down, that means that your body is really preferentially only producing that clonal immunoglobulin. So that portends the fact that maybe this patient, if those are dwindling down and the involved immunoglobulin is rising. That's a risk factor for progression. The last thing is that if a patient got a PET CT or an mri, we talked about how. Well, obviously, if you have a lytic lesion, that is a myeloma defining event. But what if you just had focal uptake on a PET scan? That's a high risk feature. Diffuse uptake on a PET scan is a high risk feature. And remember, for that slim crab, it has to be an MRI more than one focal lesion, not just one focal lesion. So if you had a focal lesion, just one, then you would say that this patient is high risk but doesn't have a myeloma defining event. And that's when you also repeat imaging. So focal PET scan uptake, diffuse PET scan uptake, one focal MRI lesion. Those are all examples of when you need to survey these patients with serial imaging, with the next imaging study being done after six months and then spread out thereafter. But that is critically important because those are other risk factors for this patient with smoldering myeloma to progress to overt multiple myeloma, which is when we really want to initiate treatment.
- [32:54]
A
And you know, Vivek, as you were just saying that, at first my head started spinning and I was like, oh, my gosh, more rules, more guidelines. But when you think about it kind of intuitively, all you're saying is if you know your slim crap criteria for someone being diagnosed with multiple myeloma, you're essentially just saying that this person almost meets those criteria, but not quite. And so in your mind, you can, can justify or at least make sense of the fact that, you know, we've already, we're already saying that smoldering myeloma patients have a high risk of progression. And so, yes, these other risk factors that we just mentioned that are not in the 20 to 20 rule are basically just things that are inching towards meeting those slim crap criteria. Is that, is that safe to say?
- [33:42]
B
Yep, that's. That's absolutely right. And then the last thing I want to say, and sorry, listeners, for this being a slightly longer episode, but this material is so important to understand, is the idea that for these patients, we've done a bone marrow biopsy. And we'll talk about this more in the next episode when we really talk about treatment for both smoldering myeloma and frontline treatment for myeloma. But I want to mention this. We get cytogenetic information from that bone marrow biopsy. Remember that FISH studies or the cytogenetic information is large chromosomal rearrangements shout out to our first episodes release the heme path series. Critically important as we think about myeloma. And there are certain high risk chromosomal translocations, high risk FISH features that make a patient, even with smoldering myeloma, higher risk for developing overt multiple myeloma. And we'll talk about what those translocations are in the next episode.
- [34:37]
A
Guys, I know that our episode was just a little bit longer than we typically have our episodes be, but I don't know about you, but I thought that was a fantastic discussion. I mean, I think we alluded to this last time, but, you know, patients with these sorts of lab findings are constantly being referred to our hematology clinic. And so being able to really understand the difference between MGUs, smoldering myeloma, mult myeloma is so important for helping us kind of care for our patients, essentially. So I want to thank you guys for helping break all this down for me and also for our listener.
- [35:18]
B
Yeah, that was a really great discussion and I really wish I knew a lot of this, honestly, even before we produced this episode. I've learned a lot and I hope you guys learned a lot and I really hope that you check out the show notes and listen to this again because this is really critical to getting to the next step of treatment of smoldering and, and treatment of multiple myeloma.
- [35:39]
C
And Vivek, I know you already said this, but yeah, be sure to go back through those heme path episodes, especially, you know, karyotyping cytogenetics episode. It's going to be super important for next week.
- [35:50]
A
Well, then, until next time, everybody. We'll see you later.
- [35:54]
B
See you later.
- [35:55]
C
Peace.