Suzanne: When we talk about early diagnosis in myeloma, it’s less about stage of disease and more about disease burden for the patient.

Rebecca: Hello and welcome back to season two of GP’s Talk Cancer. I’m Dr. Rebecca Leon and joining me again through this podcast is Dr. Sarah Taylor. We are both practicing GPs and GP leads for Gateway C. We’re both passionate about diagnosing cancer early and in this podcast we want to share our clinical experiences with you so you can make better, faster, and more confident cancer diagnoses in primary care.

So there’s some official stuff to make you aware of. We know this podcast might be of interest to anybody, but it’s really aimed at primary care health professionals. And although all patient cases are based on real stories from clinical practice, they are fully anonymised with no identifiable patient data.

Gateway C is the free early cancer diagnosis resource funded by the NHS and is based at The Christie NHS Foundation Trust. GatewayC is a national programme across the whole of England, Scotland, and Wales. Register online to gain access to free interactive courses, documentary-style videos, referral maps and more.

So today we’re gonna sit down for a coffee and talk about myeloma. With me and Sarah is Dr. Suzanne Roberts, a consultant haematologist. Welcome!

Suzanne: Thank you!

Rebecca: Lovely to have you here. And we’re gonna be talking about an area that we’ve both read up a bit on, and it’s, it’s one particularly in my practice I have a lot of elderly patients and myeloma is quite at the forefront of my, my mind as a potential diagnosis so I’m excited to learn more.

Sarah: I always like talking to Suzanne about myeloma and… but because she makes everything so simple.

Rebecca: Oh, I love that.

Sarah: And it’s, and so you always think, actually, I know exactly what I need to do at the end of this, which I think is always a real plus.

Rebecca: Fantastic. Okay. So first of all, drink okay? We always need to make sure that everybody… It’s a bit, it’s a bit cold in here, but we’re alright cause it’s a lovely sunny day.

Sarah: It is.

Rebecca: We were just saying, just off, off camera that we all got the train here.

Sarah: Yeah.

Rebecca: Which is quite exciting really.

Suzanne: Yeah, absolutely. No train strikes today!

Rebecca: Yeah. I love that. Yeah. So, just some statistics to start with. I think it’s important for us to be aware. So myeloma is the 19^th most common cancer. Interestingly, it’s most commonly diagnosed in those between the ages of 85 to 89 and I know it’s a cancer that one of the risk factors is getting older. It’s more common in men than women. So it’s the 16^th most common in men and 18^th most common for women. And a third, 31%, so just slightly under a third of diagnoses are made in the emergency settings. So it’s our job to…

Sarah: … Try and do something about that.

Rebecca: Absolutely. So can we just talk about the first case, Sarah.

Sarah: Yeah, so I… This this case, it, it’s sort of… It’s not a patient I saw, but it’s modelled on the one that we’ve got in the GatewayC module on myeloma again. So it’s, it’s a woman who, who, who… It is based on a patient who we, I see fairly frequently but didn’t have myeloma. So she comes in very frequently with lots of aches and pains and every, most weeks, every couple of weeks she’s coming in, but suddenly something changed and she was describing the pain slightly differently. And I’m always aware that whilst, you know, there’s always this thing about infrequent attenders and people who you don’t see very often, you should be concerned about them. I sort of feel we should probably be just as concerned about people who we see all the time who have things that change. So what sort of things should we be looking out for in people in that sort of age group and with new symptoms?

Suzanne: So back pain’s obviously a very, very common presentation in primary care. And the majority of patients you see aren’t going to have myeloma as a cause the back pain. Absolutely. Musculoskeletal, degenerative back pains are going to be the most common. For our patients with myeloma, it’s usually a sudden onset pain, so it’s that vertebral fracture, the collapse the vertebrate that’s causing the pain. You can also get more of a diffuse bony pain before that happens as well. So it is, it’s somebody who maybe hasn’t gotten a mechanism of injury to cause the pain but has got a new sudden pain and it usually has those red flag symptoms with it. You know that pain that doesn’t let them sleep at night. That’s continuous. It’s not related to position. It doesn’t get better when they rest. It’s not particularly made worse by moving. So that different pain that really clearly is new for them. They say, ‘okay, well I’ve had this long-standing back ache for a long time now, but this is new and different for me’. That’s something that we should really be flagging up as, as a change in their, their clinical situation. And then the other very common pain that we should be thinking a lot more about is rib pain. So rib pain isn’t something people normally complain about. So if somebody’s coming in with a, a rib pain, that feels like a bony pain. So it’ll be different from that costochondritis in the centre, usually more over to the sides in the ribs. That sort of a pain is an unusual pain, and that’s very commonly associated with myeloma. So for a patient who comes in either with a new back pain, something that might be flagging up as more red flag type symptoms, or with a rib pain who you know it isn’t saying, ‘oh well I’ve been coughing every single day for a month and that’s why I got a rib pain’, or hasn’t fallen over and banged themselves in the ribs. These are two bony pains that we should really be strongly thinking about myeloma.

Sarah: How often will they have tenderness?

Suzanne: So I guess it depends really the cause of the pain. So yes, obviously if you’ve got a new vertebral fracture, that probably will be tender if you start to press on it. The rib pains quite often are soft tissue lesions growing out of the ribs. So again, they might not actually be tender to press on always. Fractures, if somebody’s broken a rib or if they’ve got a break in the vertebra, then yes, I assume that will be tender to press on.

Sarah: Mm-Hmm. So what other things would we be looking out for in this woman?

Suzanne: So in somebody who comes with a new back pain like that, you have to be thinking about you know, the general wellbeing of the patient What else might be going on. So are they complaining of fatigue, you know, we’re thinking now about symptoms of anaemia that they might be coming in with. So what’s, you know, what this patient’s other past medical history? Are they normally known to be anaemic? If not, are they starting to complain of feeling more tired, more out of breath and reduced exercise tolerance. So yes, if they’ve got pain, it’s gonna be harder to do things, but actually, are they starting to be limited by getting more short of breath? So normally they could walk up a flight of stairs okay, and now they’re halfway up and having to pause and breathe deeply before they continue. These might be symptoms of anaemia. And then is there anything else, any other new symptoms? Are they… Anything we could link into having a high calcium level? So that’s abdominal pain, maybe feeling dehydrated. Are they passing urine as normal? Starting to think about the kidney system as well.

Rebecca: Do you remember that phrase – bones, stones, groans and abdominal… No… Say it, you can say it properly… Bones…

Sarah / Rebecca: Stones, groans and…

Suzanne: Abdominal moans…?

Rebecca: Is it abdominal moans? Yeah…

Suzanne: It’s bones, stones, groans and moans!

Rebecca: Yeah. It’s bones, stones, groans and moans. And those are all… Have you heard that before?

Suzanne / Rebecca: For hypercalcemia, yes.

Sarah: Yeah.

Rebecca: So it’s… It’s all the things you talked about, like the dehydration can cause the stones, the pain… Yeah.

Sarah: Yeah.

Rebecca: Is it psychic moans?

Suzanne: Yes, I think so because it’s confusion, a confusional state with the very high calcium levels.

Sarah: There you go.

Rebecca: There you go.

Sarah: Well, I quite like the CRAB.

Rebecca: Yes. Talk to us about the CRAB acronym.

Suzanne: The CRAB criteria. So this is for symptomatic myeloma. So these are the common presenting symptoms or end organ damage we can see with myeloma. So the C in crab stands for calcium, so we’re looking for hypercalcemia. The R is renal, renal impairment. A is for anaemia. And B is for bony pain. So for a patient who has even one of those, you don’t need all of them. We should be starting to think about myeloma.

Sarah: And is that in patients of any age or…?

Suzanne: So myeloma is definitely a disease at which we see with increasing incidence in the ageing population. So for anybody over the age of 60 who has these, we should certainly be thinking about it. But we do see myeloma in younger patients in their forties and fifties. It’s not a disease we see in paediatrics or in the teenage and young adult population. So I’d say over the age of around about 40, if we start to have concerns about these symptoms, we should be testing for it. You won’t see many 40- or 50-year-olds with myeloma, but they do exist and it’s important we don’t miss them.

Sarah: So that brings us onto the other case that we were talking about, doesn’t it, Rebecca?

Rebecca: Yeah. And then what I would like to know is exactly what primary care investigations you, you suggest that we do. But let’s talk about that second case. So it, again, was a case that we discussed. A 50-year-old woman. She was mother of teenage children, a fairly infrequent attender. She had hypertension, which was picked up a few years before and so she was coming for her annual review and annual bloods. She did discuss with the, the healthcare assistant when she was at, at the appointment that she was feeling a little bit more tired, but it was pretty vague and said she’d been quite busy. And actually, so an FBC was added onto her blood tests. And on the review of the bloods, it showed her HP was 109. And when it was compared to last year’s, it was a… It was 116. So there’d been a slight drop. And interestingly, the eGFR was 82 last year and it’d been picked up at 58. Just talk to me about that patient because to us, it’s a bit like, ‘eh, yeah’… But we’re talking about myeloma.

Suzanne: No, I understand. So these are the vague, sort of early signs of myeloma developing. So we know that anaemia it’s something which develops before symptomatic myeloma for a lot of patients. So in the three years leading up to diagnosis of myeloma, if we go back and look at blood results from primary care, we do tend to see a very early developing anaemia. And the same is actually true for raised ESR. So for patients who have no other reason to have a raised ESR that usually becomes elevated about two years before the diagnosis of myeloma. So there has been a lot of work done seeing if we can detect people at a very early stage. Who we should be screening? Can we even start reflex testing people? So you’ve gone to see your GP for one thing, we notice using artificial intelligence and that sort of technology that your blood test results have some of these features. Should we then be adding on these myeloma blood tests for patients to try and help pick people up at an earlier stage? So patients who have a new anaemia without a really obvious cause for it. So people who aren’t iron deficient, don’t have B12 and folate deficiency, myeloma should be up there. We should be thinking, actually, this is a new anaemia. This patient has no other reason for it. They don’t have lots of chronic health conditions to give them an anaemia of chronic disease normally, so why are they becoming anaemic? We’ve excluded our basic things like haematinic deficiencies. Next on the list really should be a myeloma screen, and the same with the worsening renal function. Again, it’s very minor at this stage, but if we do it again in six months’ time, we might be seeing a deteriorating pattern at that stage. So trying to pick people up early while we’re doing all the normal things we’d be doing, you know, protein creatinine ratios and that sort of thing for the renal impairment, we should maybe also be thinking, well let’s just do a myeloma screen at the same time because again, this is somebody who doesn’t have a lot of reasons for their renal impairment. Yes, they might have a bit of high blood pressure and that is obviously one, gonna be one of the really common causes of renal impairment. We shouldn’t forget other rarer causes as well, which we can intervene early to protect the kidneys.

Sarah: When you’re talking about a raised ESR, what level are you talking about? Because you know, they, they flag at anything above seven, I think, don’t they? And…

Suzanne: Yeah, so when patients present with symptomatic myeloma, we often have a very, very high ESR. You know, seeing it over a hundred, isn’t that uncommon. But in the earlier stage you know, ESRs of over 30, you know, can be seen. It’s very much, again, like you’ll see a lot of patients through primary care with rheumatology conditions, you know, who will have raised ESRs and anaemia, because of that underlying polymyalgia or rheumatoid arthritis…

Rebecca: Polymyalgia’s the one that we would probably, they would go down that… They would go down a PMR route, wouldn’t they?

Suzanne: Absolutely. Raised ESR, anaemia, aches and pains.

Rebecca: Yeah, yeah.

Suzanne: You will be thinking polymyalgia, not myeloma because it’s very common. Yes. So it’s just flagging up that, although that is the most likely explanation, absolutely. Maybe it’s not for every patient. And keeping that in the back of our mind just so we can get those myeloma blood tests done early. Because when we test for it, we can diagnose it and it’s just having that thought in the back of our mind. Let’s just make sure we don’t miss something that’s easy to pick up on a blood test.

Sarah: So with either of these patients, the 70-year-old with the back pain, or the 50-year-old with the new onset anaemia with no cause, what would you… What should we be doing next?

Suzanne: So for our myeloma tests, we always need that haemoglobin. So looking for anaemia, so full blood count, the renal function, so U&E, a bone profile, looking for the calcium. And then the test that we think of as the myeloma screen. So that’s just serum immunoglobulins with electrophoresis. And then also the other part of the myeloma screen, which is your light chain testing, which will vary from location to location within the country. But it’s either that urine test for the Bence-Jones protein. Or on the blood test, the serum free light chains. And there’s a little bit of local variations still in the country as to which laboratories offer which test.

Sarah: And I think we’ve talked about this before, but actually just doing the immunoglobulins and electrophoresis misses quite a lot, doesn’t it?

Suzanne: Yes. It will miss patients who have a light chain only myeloma or a light chain only MGUS, which whilst it’s not the majority of patients with myeloma, is still very significant because these are the patients that usually present as an emergency with renal failure and may even need dialysis from it. And sometimes when we look back, patients have had that, that test for myeloma, but only the immunoglobulins and electrophoresis. Sometimes those tests are abnormal in the sense that they are all, the immunoglobulins are all low. Now, that’s not been reported as normal, but there’s not been a paraprotein present. And so for somebody who isn’t maybe an expert in myeloma, hasn’t seen this before, there’s no paraprotein present. Therefore, that equals not myeloma in their mind. and they’ve not really realised that seeing all the immunoglobulins, the IgG, IgA and IgM all being very low, actually is in keeping with a light chain myeloma.

Rebecca: That’s interesting.

Suzanne: So unless you’ve done the other part of the myeloma screen, you will miss about 15% of patients.

Sarah: Do you know whether you can get serum free light chains?

Rebecca: Yes, we can.

Sarah: Yeah, we can too. Which is, I think you’ve said is better because the return rate is poor for urine.

Suzanne: Yes, so the problem with the urine is that it needs to be a fairly concentrated sample, so an early morning sample. So that patient who’s coming after lunch, who’s just drunk, you know, a pint of water is gonna give you a very dilute sample. Or you’re gonna send ’em home with a pot and say, ‘can you return this tomorrow?’ When we order the rates of return of those urine samples, it’s actually very low. It can be you can miss as many as a third of patients who just don’t bring the sample back. And I’ve seen that in my own clinical practice, we had a patient with light chain myeloma that had been to see their GP had had their immunoglobulins checked. They were all low. They didn’t flag that up as potentially myeloma. The patient never brought the urine sample back, and then they came in as a secondary care emergency admission about a couple of weeks later, due to the back pain and the vertebral fractures.

Rebecca: Interesting. We actually have, I think on our screen it says, actually says ‘myeloma screen’. So you press it and it, and it brings up both which is quite helpful.

Sarah: Yes, definitely.

Rebecca: Because you’re absolutely right. People would just do immunoglobulins and they wouldn’t, that’s something, it’s a real learning point for us. I just wanted to just mention something about the 50-year-old, which we, which we talked about when there’s no cause for the anaemia, because I think that’s really important because at this age a lot of 50 year olds will not be menstruating anymore, and so that won’t be the cause of an iron deficiency anaemia. So we’ve just got to be aware of that because if it’s a woman who was 42. It’s likely that they probably still, still are, and they might still be having, particularly if they’re perimenopausal, their periods might be heavier and there might be a reason for an HP of 109. So we’ve got to put, I do say we’re like detectives, aren’t we? We’ve gotta put all these different, she’s 50, she’s probably gonna be menopausal. Plus she’s, you know, plus she’s got a low HB and we’ve gotta put all these in. So that’s important.

Sarah: And then you’ve gotta get rid of the things that are distracting. So she’s tired – is she tired because she’s menopausal?

Rebecca: Yes!

Sarah: And, and, and you’re sort of trying to work out the significance. I think that the bit that it’s interesting isn’t it, the thing we we’ve talked about it lots of times, is the ‘three strikes and you’re in’, so actually if you’ve got somebody with two or three new symptoms or the same symptom two or three times, and you haven’t got a good explanation. And actually, if she hasn’t got heavy periods and it’s new and the iron’s normal and she’s not… All of these things start to, you haven’t really necessarily got a good explanation for why the haemoglobin’s dropping. And as you said, I suppose the, the beauty of this is that actually it’s really easy… For Rebecca, all she needs to do is tick one box and send the patient off a blood test and then we’ve got an answer! Presumably if we’ve got a negative myeloma screen that includes electrophoresis and serum free light chains, then we can be reassured that this isn’t what’s going on.

Suzanne: Yes, so we do have that very, very, very rare condition. The non-secretory myelomas, there’s always an exception to the rule.

Rebecca: Always.

Suzanne: Always! Yes.

Rebecca: Nothing’s a hundred percent.

Suzanne: No. But from a primary care perspective, yes – if you’ve got a myeloma screen that has no paraprotein visible and your serum free light chain ratio is normal, or your Bence-Jones protein in the urine is negative. Then yes, you can be, very, very reassured this is not going to be myeloma.

Sarah: I wonder whether I might pick up more myelomas than I have do coeliacs. Because I do lots of coeliac screens and don’t diagnose very many at all. I do lots of thyroid function tests and don’t diagnose a huge amount.

Rebecca: So you are thinking about the more vague…

Sarah: Well, just the tests that you do when you’ve got a patient who’s tired…

Rebecca: You mean, the obvious one is the 70-year-old man with the back pain, but you are thinking that there might be this age of…

Sarah: Yeah, I mean I’m not suggesting that we tick them on every patient but actually…

Rebecca: Have a higher…

Sarah: … A higher, just bump it a little bit higher up the list of things that we do. I mean, you know, we do quite a lot of CA125, so we do FIT now in anybody who moves pretty much! But I still think that probably, and I don’t know whether the research backs it up that actually probably myeloma is still quite low on the GP diagnostic list.

Suzanne: It is. Which is why we get that third of patients presenting as an emergency. And that’s really where we need to be working on. Trying, when we talk about early diagnosis in myeloma, it’s less about stage of disease and more about disease burden for the patient. And we know that when we diagnose people in primary care, our one year and five year survivals are higher than if they come in as an emergency.

Rebecca: So can I just ask, so as you said, we see a lot of patients and we see a lot of people with back pain. We see lots of people with tiredness, and I see a lot of women in the late forties, early fifties who are tired and money’s on it, that they’re probably perimenopausal. What’s the next stage do we do with this woman who’s got an HP of 109? Do we, do we say, right, come back in a month and we’ll recheck your bloods, and then they add the myeloma screen? Do we need to do anything within the week? What, what do you suggest that we do?

Suzanne: No. So at this stage, it’s clearly not an emergency. You know, their renal function is good. If not completely normal. The haemoglobin is good, if not completely normal. They’re not complaining of any severe bone pains. You haven’t got an emergency on your hands at this point in time. We have got time to, you know, see what happens with these patients. We will be bringing them back and a month is a reasonable interval there. You can check the haematinics, make sure they’re not iron deficient. This isn’t somebody who’s suffered for years with menorrhagia, who’s still recovering from that. We know that she had a normal haemoglobin previously, so something’s going on. But yes, it could be something very simple. She’s had a really nasty bout of the flu and she’s just recovering from it.

Rebecca: Yeah.

Suzanne: So giving it a month to see what happens in somebody where we’ve just got some very slight abnormalities is not at all the wrong thing to do, but they do have to then be safety netted to come back. That’s very important. And not just left for another 12 months. Because it’s, it’s these patients who will slowly but surely progress. So if this is a very early sign, we might be a year or two years away from a symptomatic myeloma with end organ damage. We want to get them before that happens.

Sarah: Is a month about that because I know, my husband’s a radiologist and he often says that a month or two months on scans is, is too short. So because, so differences can be so small that you actually can’t really see them so you need to leave at least three months to… Is a month about, right? Would you, if it was, if you’d got a myeloma would you expect that 109 to have come down to 107/108? Or would you just be looking to see whether it had gone back up?

Suzanne: I think you’re looking to see, has it gone back up? Has something else happened that she’s recovering from? And to make sure there’s not a worse drop happening.

Sarah: Yeah.

Suzanne: You know, is this your patient who’s going to turn out to have acute leukaemia or something?

Sarah: Yeah.

Suzanne: You know, there’s lots of other things that can cause drops in the haemoglobin. So we’re look, we’re really at that stage safety netting to say, well, actually, has it got much worse in a month? In which case, it might not be myeloma, it might be something else. Or has it just gone back to normal because she was post-viral or something like that?

Rebecca: So a, a patient who you are pretty concerned has got myeloma, either the screening comes back as, as showing it, um, and you want to refer them into secondary care. So we’ve got the kind of, the bit in the middle when we know that we’re gonna, as in the patient that we’re gonna recheck in primary care and, and review them and see them, what’s changed. And then we’ve got the patient who, who either has got, is symptomatic, as in has got the bone pain or has got very abnormal bloods. And the ESR is another one that I’ve really learn from today. What do we do then? Because which of those patients do we almost refer in as an emergency? And which the ones are you happy for us to refer in under a suspected cancer?

Suzanne: So we’ve got the very emergency patients. These are the ones where we might be suspecting metastatic spinal cord compression. So the people with the very severe back pains who are starting to develop neurology symptoms. They are straight into hospital. The people with very high calciums. So if you’ve got a calcium of, you know, three or something like that, they’re going to need to come in as an emergency for rehydration and management of that. The very low anaemias or pancytopenia patients are going to need blood transfusions and inpatient management as well. So those are the ones that we’re thinking actually need to be admitted to hospital.

Rebecca: Yeah.

Suzanne: In terms of other patients where you’ve really got the ones that need a suspected cancer referral, and then we’ve got that whole group of patients who have MGUS, where you’ve suspected myeloma for any reason. So a bit of a change in back ache. You’ve done the myeloma screen, it is abnormal, but is this potentially myeloma or is this the benign precursor condition, MGUS. Which is actually a routine referral to haematology.

Rebecca: Tell us about MGUS. Something that we don’t really know much about.

Suzanne: So MGUS is the benign precursor to myeloma.

Rebecca: Yeah.

Suzanne: So all patients who have myeloma will have had this precursor state, but actually the majority of patients who were diagnosed with myeloma aren’t known to have a preceding MGUS. They’ve never been tested for it before. We don’t currently screen for MGUS, and that’s because these are well, healthy individuals. A patient who has an MGUS, has a roundabout a 1% chance each year of progressing to myeloma. So it’s not high. So we’re not out there actively looking for them. But when we do find them, we offer monitoring for it to see if we can get them early before they change to myeloma, if they’re going to do so. So it’s not uncommon in an older patient for you to look for myeloma due to a back ache and actually find a coincidental MGUS.

Rebecca: Okay.

Suzanne: And it’s trying to pick out these patients who can come to haematology routinely. Versus the ones who are likely to have myeloma who need a suspected cancer referral. We used to say the incidence of MGUS was about 1% in the over sixties, 3% in the over seventies and 5% in the over eighties. Actually, the data from Iceland where they’re doing a really large population study shows it’s actually much higher than that, might be 10% of the over eighties…

Sarah: So you don’t want all of those on suspected cancer referrals…

Suzanne: We can’t have them all. We’d collapse our service. If you went out there and tested all your over eighties for myeloma. 10% of them have MGUS. We can’t accept that on a two-week-wait referral. We haven’t got capacity. Absolutely. Also, diagnosing MGUS for a patient is not very helpful. You’re telling them there’s something wrong, but it’s nothing to worry about, but we’re going to monitor for you and it may become cancer but it probably won’t, but we don’t know, so we’re going to watch it anyway. There’s a lot of work being done around that and whether psychologically that’s… That’s beneficial for the patients ’cause it can cause psychological harm. It’s over medicalising. It’s also putting extra burden on our health system that’s already quite stretched financially. So it’s a very difficult one from, from a haematologist point of view, the definition between MGUS and myeloma is usually straightforward, but I understand it’s not from a primary care point of view because it’s not something you do regularly. We’d always rather see them on a cancer pathway than have them out in primary care and them coming later as a routine. Everybody should be triaging their referrals. So anything you send through on a routine referral should be looked at and somebody should be looking at that and saying, ‘well, actually I think this could be myeloma rather than an MGUS’, and picking them up and pulling them through sooner. So there shouldn’t be a lot of concerns about that but really trying to get the MGUS through routinely and the myeloma’s through as a two-week-wait.

Sarah: Presumably, I mean, I’m a great fan of advice and guidance and I would sort of…

Suzanne:  It’s brilliant, isn’t it!

Sarah: And and particularly for haematology, it works really well, doesn’t it? ’cause you’ve actually got most of the information you need in front.

Suzanne: Yes, Absolutely. And then you’ll have a haematologist which will review all the blood test results and the history you give them. So given the full history is really, really important, we can only go off the the information we’ve got, but yes, absolutely we’ll be able to say then we think this is likely to be an MGUS. Send them routinely. Or you know, depending on how long the wait is, we might say, well, can you do a blood test in a month’s time? And just make sure things aren’t getting much worse, in which case we will need to see them urgently.

Sarah: Yeah. And then, and what about the reports? So you’re saying that it’s, you know, I, I suspect there’s a whole heap of primary care professionals who aren’t confident in looking at immunoglobulins and, and and diagnosing MGUS versus myeloma, will there be something on the report to tell us?

Suzanne: So obviously the reports do vary trust to trust. They will always say the amount of paraprotein present. So you’re looking for the paraprotein, not the total IgG, or IgA or IgM. You are also… They will say on the light chains say we’re looking for the ratio, not the individual light chains. So the electrophoresis result that comes back tends to just say, there is an IgG kappa paraprotein present, something along those lines. And it will give you a number. Same for the light chain. You’ll get a number for the kappa or a number for the lambda, and then a ratio. Now there’s a really, really helpful guide that’s been produced by Myeloma UK. We’re also working very much individual cancer alliances around advice for GPs on how to interpret these tests. Because yes, if you sent every paraprotein up, well those would be a lot of MGUSs in there, which we didn’t need to see urgently. And the same if you sent every patient who’s got a slightly elevated kappa light chain up. Well, most of these will actually be normal or inflammatory results and not in keeping with MGUS or myeloma. So the Myeloma UK guide is very, very helpful and it basically says which levels to think about referring up as myeloma.

Sarah: It’s one of those things, isn’t it? That you, you, you sort of, you think you’ve got it straight in your mind and then by the time you actually see somebody who, where it’s relevant because it doesn’t happen every day, you’ve forgotten and you think, ‘oh, I can’t remember what to do’. So actually we can attach that to the show notes as well, can’t we?…

Rebecca: Oh, absolutely.

Sarah: … The guide. And I think that it’s useful just to have a guide that we know everybody in the country can access.

Rebecca: I, I think also what I’ve taken away from this is that we had a, a very good haematologist at my local hospital who’s since retired, who I was able to just, speak to and just talk to and, and, and I’m thinking now that we don’t have that, but I would like to pick that up and maybe speak to the trust and find who that person is because I think that will help my primary care colleagues, because you say…

Sarah: I think advice and guidance works really well.

Rebecca: … I think it, it works so well, but particularly in haematology. I have a patient with a smouldering myeloma. Okay. And I’ve seen it on clinic notes and I kind of…

Sarah: Sounds weird.

Rebecca: It does. It’s a great word. Smouldering or indolent myeloma. These are, I presume, asymptomatic, are they, they’re not the same as MGUS?

Suzanne: They’re not the same as MGUS. So it is a bit of a spectrum from MGUS to asymptomatic or smouldering myelomas through to symptomatic myelomas.

Rebecca: I think it’d be a good name for a band – a smouldering myeloma. Is that inappropriate?

Sarah: Possibly!

Rebecca: Yeah. Carry on. Sorry. Apologies. This is when we had the end of the day when we’ve had a, we’ve had a lot of things. So you’re talking about your spectrum.

Suzanne: So your symptomatic myelomas, these are the ones we absolutely must have under haematology. They have active cancer condition, they need treatment. Otherwise, they’re going to run into problems with end organ damage. They’re, they’re on treatment those patients. The MGUS patients have the benign precursor condition. They are not going to have any treatment. They are being monitored, and there’ll be local variation, in how these patients are monitored. Some will stay under secondary care, some under primary care. There’s a, there’s a bit of local and regional variation with that, but they will have regular monitoring. Patients with smouldering or asymptomatic myeloma sort of fall in the middle. They’re the patients with the higher paraprotein levels. So by the time you’ve got an IgG paraprotein of more than 30, you are falling into the smouldering myeloma group. And if you’ve got a, when we do the bone marrow test, if we’re worried about a patient, we’ve gone as far as doing a bone marrow test, we define myeloma as having a bone marrow percentage of more than 10% plasma cells. So again, they fall into the smouldering myeloma group. These are patients who we’ve got enough to diagnose myeloma, but they haven’t got the end organ damage that goes with it yet. So they’re in the asymptomatic category. They have a higher risk of, of, progressing towards symptomatic myeloma than the MGUS’ do. But again, not every patient will progress to symptomatic myeloma. So they’re, they have closer monitoring and observation than the patients with MGUS. But again, we’re not treating those patients at present. There’s not the evidence base to do that. It has been looked at, but at the moment they’re not actively treated, just monitored closely.

Rebecca: Okay.

Sarah: And well, we, we talked a little bit just before we started the podcast about treatment. You were saying that once you start treating a patient with myeloma they’re on treatment for life, is that right?

Suzanne: Essentially. So myeloma is not considered curable. So we have treatments nowadays, although we have treatments such as autologous bone marrow transplants we’re still using. We have lots of different chemotherapy options as well. We have many different lines of treatment. It’s not considered a curable condition. A lot of our patients, even when we treat them very intensity to begin with, we’ll then put them on maintenance treatments so that continuous suppression of the myeloma is very important. So yes, they’ll, once they’re diagnosed, they’ll always be under the haematology department.

Sarah: Right. And you, and just, just to go back to that, you’re saying that early diagnosis is important not because it’s a stage of diagnosis, but more because of the impact of the disease on other organs. Is that right?

Suzanne: Yeah, So staging myeloma is very different to staging other cancers. It’s not the same as solid tumours. Most of our haematology cancers aren’t staged in the same way at all. So when we stage myeloma, there are lots of different biomarkers we look at, and we’re looking at cytogenetics, the DNA changes inside the bone marrow. We’re not actually looking at how it’s affecting the person or where it is in the person, what damage it’s causing. So for a patient, the stage and how they are might actually not feel the same at all. So we can diagnose patients at stage three myeloma who actually are asymptomatic and don’t need any treatment. It’s equally possible to diagnose somebody with stage one myeloma who presents with a vertebral fracture and needs treatment straight away. Stage does link into long-term prognosis but that’s with the biology of the disease rather than where it is in the person. In terms of early diagnosis, it is actually much more important to prevent that end organ damage. That’s the symptoms, the morbidity to the patient themselves, how they feel, the impact on their quality of life, and that’s where we’re working on at the moment is can we prevent these emergency admissions, which we know also really impacts on long-term survival and quality of life.

Sarah: Is there a bigger percentage of emergency admissions in younger patients or is, is…? Because you were just saying they’re more difficult to diagnose.

Suzanne: It certainly feels like there is, yes. We know about a third of our patients present as an emergency, and yes, the younger patients, the ones who, who don’t have that regular visit to their primary care team, having those routine once yearly or twice yearly, blood tests and nurse check-ups and that sort of thing who are busy with children and jobs. They’re the people who put it off and put it off and ‘I’ll get better. I might think about it next week’. And they do end up coming in as emergencies. Absolutely.

Rebecca: Wow.

Sarah: I know!

Rebecca: As you said, so amazingly explained. Thank you very much. And what a, a lot of take homes…

Sarah: So what’s your key learning?

Rebecca: CRAB.

Sarah: Yeah.

Rebecca: I think CRAB is a great acronym. We love an acronym on this program. The calcium, the renal dysfunction or failure, the anaemia and the bone disease. That’s really important for primary care. You’ve also talked about the primary care investigations. The dual test. Really important. And also I’m gonna go away and do a piece of work of getting some haematology advice that we can on my speed dial.

Sarah: I think that the ESR is something worth thinking about.

Rebecca: Yeah, absolutely.

Sarah: And the undiagnosed, new anaemias and just having that just… I think it is just bumping that myeloma screen up my investigation list.

Rebecca: Up your differentials.

Sarah: Yeah, because it’s, it’s quite easy to do really. And it does give you an answer.

Rebecca: Okay. So, can I do some key takeaways? We’ve talked about ours. But as you say, think myeloma have it, have it up there, particularly with the older patients, but don’t completely dismiss it with the younger patients. And it can be in that big mix up with the menopause, which honestly gives us such headaches, doesn’t it? But yeah, so think myeloma, particularly in the patients with new back pain, and I think you described almost that kind of bony pain really well, rib pain, different from costochondritis and a new anaemia, and almost just keep an eye on whether it’s dropping. Remember the acronym…

Sarah: CRAB.

Rebecca: CRAB. ESR, the dual myeloma screen. And also I think it’s interesting what you’ve talked about, the staging of myeloma is different. That actually a stage three versus stage one is just, it doesn’t mean, what it sounds with other solid tumours.

Sarah: Yeah.

Rebecca: Thank you very much.

Sarah: I told you, I told you she’d make it sound easy!

Rebecca: You did. You did. So, and, and, and thank you again. And it was lovely to meet you.

So that’s it for today. Thank you to Sarah and Suzanne, and we’ll definitely be having you back on.

Thanks for listening to this podcast from GatewayC, we hope you’re enjoying this series. Please do support this podcast by leaving us a review or rating, wherever you get your podcasts. And if you’ve got any topic suggestions for future episodes, we’d love to hear them. Please do include these in your review. If you’ve found this or other episodes interesting, or helpful to your practice please do share it with a friend or colleague. It really does help to spread the word. We’ve got a free myeloma course available on the GatewayC website. All reference studies and guidelines are in our show notes. Thank you again for listening and thank you to our producers, Jo Newsholme from Rethink Audio and Louise Harbord from GatewayC. See you again soon.