Chapters Transcript Video Don’t Forget Multiple Myeloma right. Hello. My name is Dr Ian Sylvia's I'm the Chief off myeloma at Russell Park Comprehensive Cancer Center in Buffalo, New York Today, I would like to talk about the topic called Don't forget multiple myeloma. We want to talk about things that might give us a hint that the patient might have multiple myeloma, since it's rather rare. But oftentimes the symptoms that patients show with multiple myeloma are very common. So I try to differentiate and help you toe find out which patient really needs a work up for multiple myeloma on which patient might not need that. The learning objectives off this activity is to get you some insight into the characteristics that place patients in a high risk to have multiple myeloma or symptoms that should lead toe work up. For multiple myeloma, you should be able toe, identify possible treatment paths for multiple myeloma patients and also identify differences between the common symptoms that can be myeloma or are not multiple myeloma. As you know, multiple myeloma is a malignant disease. The median age at diagnosis is 69 years of age, so around 70 patients have the highest have kind of the peak off multiple myeloma incidents. It's more common in male than in female. 3 to 2 is three ratio there. The disease is called a cost by proliferation and infiltration off monoclonal plasma cells in the bone marrow. They are very dependent on the bone marrow, so we oftentimes also need bone marrow for workups of bone marrow. Biopsy is important for work up because those cells are very dependent on their micro environment in the bone marrow. At the moment, multiple myeloma is considered to be incurable in the vast majority of patients, which is something that we have to keep in mind because also, we think that if we finally get a cure for myeloma, it will most likely be in patients in early stages. So early detection is very important in multiple myeloma. Median survival or five year old world survival is about 50 to 75% also depending on risk stratification on treatment that the patient can get and of course, age, place relevant factor, but much more the biological age than the chronological age. We have about 30,000 new patients per year in the U. S. And is about 1.8% of cancers in the United States, and also it is about the second most common hematology cancer are. In general, the path of physiology is very helpful to know there are four major symptoms that are also always talking. My patients about the plasma cells, as I mentioned, are infiltrating the bone marrow and are replacing the immature poetic bone marrow. So this is something that we seaside opinions from. And this is one off the major path official logic path that are going on another thing. And that's also very important because it's one off the major symptoms is bone destruction. As you know it can cause hostility. Galicians can weaken the bones, which eventually causes fractures off the bones and also pain. And, in the worst case, neurological issues. Hyper Cal Sr is connected to that. We have in my mind, Loman over activation. Off the bone eating sells the Austro class, which lead to the bone destruction but also can solve basically calcium out off the bone on bring it into the bloodstream, which then results in hyper Kazimiyah. Another reason for diagnosis can be a renal insufficiency. Those multiple myeloma cells produce proteins that go through the kidneys and can cause kidney damage together with the hype academia, which, of course, can also cause kidney damage with a case report. Here is the patient I saw in August 2018. The first symptoms occurred about four months earlier, which is again a sign. As I mentioned, it's very important to diagnose early. So I took this patient about four months to get a diagnosis. He felt well until then he was a marathon runner, actually was training a lot. He was very active and all of a sudden or kind of, gradually, even Mawr. He developed this fatigue. He was tired. He could not do his work out, as he asi usually did. And then he started to get bone pain. It was mostly in the spine and the threat. Six. Spine In the lower back, an X ray showed not really much abnormalities on. That's something I want to go into to the sensitivity off. The diagnostic techniques that we use is very important, especially in multiple myeloma, and we'll go into more detail later on during this talk. So X ray was negative. He had an infection off the upper respiratory tract, which, okay, had not too much impact on him, but it was something that he usually didn't get because it was in really great shape before someone outside started his work up. And it showed that because the reason for the work up or for kind of increasing the worker because the symptoms until then we're kind of not very impressive. But then his pain got worse and someone did the C t on him a city chest, abdomen, pelvis. And this revealed small hostility lesions in his skeleton. And he actually already had compression fractures off several vertebral bodies and also rib fracture. So the pain was explained at that point. Further work up, then reboot multiple myeloma. But as I mentioned, multiple myeloma is rather rare, as I said. But on the other hand, back pain is rather common, so you know that about 15 to 20% of adults have new back pain. You on set back pain in a single year, which is obviously rather common compared to the very rare multiple myeloma, 50 to 80% off us off. Everyone has about one episode off back pain during the lifetime, so back pain is very common as you can see. And, as you obviously know, 60% off those patients recover within a few weeks, and even 90% recover within a little bit longer period of time. So back pain that recovers is something that is very, very common. And even if you go longer, if you have three months than almost all the back pain is gone. Some a chronic, as you know. But that's a rather low percentage. Serious causes of back pain are rather rare. All kinds of cancer, for example, are rather rare as a cause of back pain, but it is. It's around 1% but it iss there, and we have to be aware that back pain that is prolonged that goes beyond those 12 weeks, for example, should really lead Toa mawr sensitive. Work up the kind off symptoms or the characteristics off the symptoms. Off back pain in multiple myeloma is often times that it's rather sudden. Oftentimes, those patients have some fatigue and have other symptoms, but oftentimes they because they're in their sixties and seventies, mostly they blame that on well and getting older. And then now I'm getting back pain. Of course I'm getting older so Just having back pain when we get older is nothing that would people mostly not what people bring people to the doctor. But the back pain in myeloma is persistent. It's oftentimes getting worse over time, so it's not disappearing after a few weeks or after some physical therapy. Additional symptoms, as I mentioned, can be fatigue. It can beam or infections. The patients have a lower immune function. They can get kidney issues, which are oftentimes, as you know, also not very obvious to the patient. If there's no work up for it and also neurological issues, once it can be from the hyperglycemia, it's oftentimes systemic, then. Or it can be peripheral neuropathy, which can be related to the multiple myeloma. Or, of course, when there's a fracture. It can be acute onset neurological issues. Some patients have weight loss. It's not very common in my Loma, same as be symptoms in multiple myeloma. Oftentimes, those patients don't have those symptoms. It's very important to know that their racial differences, the highest incidents on off multiple myeloma is in patients off African American group, so they have actually three times higher risk. For example, as Asian Americans and the Caucasians are somewhere in the middle. As I mentioned, the median age at diagnosis is 69 years of age. It's more common in elderly patients, but of course, we also have very young patients. So it's becoming even more difficult in a young patient to diagnose myeloma because, as I mentioned, it's even rarer in elderly patients. It should definitely be on the list off differential diagnosis. It's not. I mean, it can help us. But African Americans haven't earlier onset off myeloma. They have a better prognosis overall statistically, but they haven't earlier onset. So we have to keep in mind that some patients can have the diagnosis earlier and then, while Caucasians have it, uh, rather a little bit later. So I I think that's just interesting to know. It's not really changing how we work up those patients, but to keep in mind that African Americans with back pain and all the mention symptoms might have a multiple myeloma, even if they're younger than the median age of diagnosis of myeloma in general. Interesting also an observation that patients have different symptoms at their first diagnosis, so anemia it's more common in African Americans, bone disease more common in Caucasians, so that's also something to keep in mind. Myeloma is not a hereditary disease, but there are some families with the higher frequency on. There's currently a study going on out off the Dana Farber Cancer Institute in Boston, where they're screening first degree relatives off multiple myeloma patients and actually all African Americans in a certain age range. So that's It's a so called promise study. And earlier studies have already or analysis have already shown that patients with first degree relative with multiple myeloma have a higher risk to develop myeloma or an Angus and early stage as well. So what should we do when we have the suspicion of multiple myeloma? We should definitely do family history. As I mentioned first degree relatives. Sometimes patients report that the patient or the relative had, for example, the cancer had. Oftentimes, it's called bone cancer, which is not true in myeloma because it's a bone marrow cancer. But oftentimes that's what patients remember. We should definitely do a blood count to look for anemia, obviously, and also other side Pena's renal function. It's important it's still recommended to do a 24 hour urine because we see how the excretion off the protein over a whole over the whole course of the day is in. Those patients on electro freezes and immune fixation are that the very specific test for multiple myeloma? So this is very important to keep in mind. We should look for the involved and the non involved. Immunoglobulin is because that is related to the immune function off those patients and kind oftentimes explain their higher risk of infections. And then there's the Serum Free Light Chains essay, which is rather specific for myeloma but has to be used carefully because mythological issues even independent off my turban myeloma have an influence on it and also infection racist the same free light chains. So it's very important to look at the ratio off the Kappa Tau, the Lambda Light chain, off the lander to the capital. I chain to see if this is off. If the ratio is normal, the elevated light chains can just be related to something else as I mentioned myeloma, and it's precursor diseases are kind of characterized by the infiltration off the bone marrow, so we need a bone marrow biopsy to see that the bone marrow with monoclonal plasma cells. If it's less than 10% it's Aunt has no symptoms and the molecule protein in serum and urine. It's less than 30 g per leader or 3 g per daisy leader. It's called monoclonal democracy for undetermined Significance, or MGA's Smarter in multiple myeloma is somewhere in between. It has more than 10% plasma cells in the bone marrow and or more than 30 g per leader or 3 g per daisy leader off monoclonal protein. But by definition, smoldering myeloma patients have no symptoms, and multiple myeloma is as soon as there are symptoms, and it's more than 10% last myself in the bone marrow. The goal in research right now is to kind of get rid off the smoldering myeloma. Because Angus, we just monitor. Those patients don't need treatment. Multiple myeloma definitely needs treatment, and it smoldering myeloma. There are a lot of attempts to differentiate between smoldering myeloma patients who benefit from a treatment because their arm or like multiple myeloma and patients that have smoldering myeloma but are behaving or that disease is more behaving like MGA's. So this is at the moment in the process we still have this definition of smoldering myeloma, but we should keep in mind that those patients might progress sooner than, for example, a patient with monoclonal Ganapathy for undetermined significance. Mga's itself. It's rather common, actually. If you look here in men after a certain age, it's pretty common. This is percent, so up to 10% in elderly male patients and also going up in elderly women. As you know, everyone is getting older nowadays, or almost so. There's a high risk to have an Angus, which should not develop into myeloma but should be monitored. But it's more common in elderly patients, so it's something also to keep in mind. But as you can see here, it's a much higher frequency than my Lomas. A lot off. Those patients really never develop myeloma. The risk is actually for Angus, about 1% per year to develop a malignancy. Could be myeloma could be one storms, micro global anemia and in smoldering myeloma, and you can see these changes over time. In smoldering myeloma. The risk of progression is about 10% per year, but if you look here, there are patients who have ah progression risk off kind off like Angus with this 1% per year. But there are also patients with a very steep with a very high risk to develop the disease within the first few years after their diagnosis. So this is something to keep in mind. Smoldering myeloma. We really have to differentiate between someone who is more behaving like an Angus patient versus someone who already has myeloma that has not really cost any symptoms yet. And there's a lot of research and a lot off studies going on for this. What's also important if a patient is diagnosed with Angus? This is kind of a way to show how the deceased develops over time, and we see that a lot in our patients, often times those patients stay in a very stable, kind off disease stage over a long period of time, and then all of a sudden there's an increase in their markers, and this is the point where we have to be very careful with Angus patients because then they might develop the myeloma. Pretty soon there's some component off genomic revolution, and we see that the disease kind of picks up the dynamic, and that is the point where the patient should really get more work up on the biopsy again, emerging again on the 24 hour urine to look for the kidney function. As I mentioned, myeloma, bone disease is very important at first diagnosis. The radiographic findings. This is rather old study, but it's still true. Political Asians are found in about 70% of patients. Ah, lot of patients, actually almost a quarter already has fractures in their bones so that it's important. Compression fractures off the spine, as you can see on the right side, are very relevant. And some patients also can have osteoporosis or osteoporosis of sister roses is rather rare, so we should think about more common cancers like prostate cancer, for example. But it also can occur in multiple myeloma. I talked about the sensitivity to detect the disease as I mentioned this patient that we had in our case report had X ray, which was negative and later on it, see t the lesions were found and I'm propagating really to u C T instead of X ray even for screening, because, as you can see here on the left, this was a patient of mine who had pain in her hip. We knew already she had multiple myeloma with the X ray she brought from outside, and we saw basically nothing nor syphilitic lesion. And then on the right side you can see where the arrows point to. There was even a soft tissue tumor growing out of the pelvis, and there was a lot off bone destroyed, and this was really within a few days. Those two images and you can see the C T picked up the soft tissue part with the bone destruction, while X ray was still negative. So it's very important to keep in mind that we have to be very careful. Based on all these path of physiological factors, there was a classification 2000 and three, where the diagnosis, as I mentioned, MGA's is less than 3 g per daisy leader and less than 10% monoclonal plasma cells in the bone marrow and no r o. T. I. So no related organ or tissue impairment. That's what R. O. T. I stands for. Smoldering myeloma has a higher level, but no related organ or tissue impairment and then symptom. Multiple myeloma is basically characterized by the presence off this r o t ice and you can see here. As I mentioned, we they were summarized as the so called crap criteria See for hyper Casimir are for renal insufficiency A for anemia and B for bone disease. So these other factors that differentiate the symptomatic multiple myeloma from a non symptomatic multiple myeloma. So this is the old definition and the new definition added to this crap criteria the slim, which is 60% of plasma cells in the bone marrow. Because this was identified in smoldering myeloma patients without real symptoms without crap criteria to be a high, a strong risk factor to develop multiple myeloma. Another symptom is the light chain ratio. As I mentioned, more than 100 is considered high risk off development off multiple myeloma and more than 100 mg per leader in as an absolute count is supposed to be a marker off progression and also focal lesions in memory, which is defined as findings in the Marie before they have been austerity. Galatians Because, as you know, austerity Galatians would already qualify for bone disease. So this new slim crap criteria with the four crap criteria and the three slim criteria is considered a patient who needs multiple multiple myeloma treatment, even though they might, by definition of 2000 and three still have a smoldering myeloma. I have no criteria, so these criteria toe initiate a treatment in a patient. As I mentioned, it's very important to look for the plasma cells in the bone marrow for the percentage back in the old days when we didn't have more sophisticated techniques. Oftentimes, colleagues also look for the morphology off those cells. That's not that important anymore. We have set a genetic changes that we can assess, but it is still important to see how is the percentage of glass facades in the bone marrow. The treatment has changed over the last decades, actually already. And as you can see here on both evaluations, there was not a lot going on about 20 years ago. And then all of a sudden there were new treatments that have been developed, and we have them now in the overall survival of patients. Together with the development off, new off new treatments has really significantly improved, and here's kind of timeline when those three treatments came on the market or were used in myeloma. And as you can see, it's getting very dense around 2010 and 2020. So we have a lot off new approvals for multiple myeloma, Actually, not that new anymore, but still ongoing new research with new approvals even this year. So it's very helpful that we have so many options and we treat myeloma as I mentioned, it's still not curable, but we treated as a chronic disease where when 11 treatment doesn't work anymore, we give the next treatment in the next treatment. So it's very important to diagnose myeloma because we have so many options and patients can live really a long life with most of the time good quality of life, which is very important and very encouraging, of course, and it's not ending here. There are new treatments that are in development. There's still a lot off ongoing clinical trials. I think one of the most promising ones are car T cells, where T cells from the patient, our genomic Lee, modified and then given back to the patients that they attack the myeloma cells. So very, very promising developments. Even in the near future, when we see myeloma, patient for the first time and think about treatment. It's important to differentiate its this patient stem cell transplant candidate or not. So high dose chemotherapy with autologous stem cell transplant is still the standard of care. Ineligible patients so it leads ability for a long time, was based on age. Nowadays, we know that age. The chronological age is not as important as the biological age, so we recommend toe. Look out for patients who have a good performance status much more than just a younger age. Of course, younger age patients are also eligible. Stem cells should be able to be collected, but that usually happens in most off the patients. Organ involvement and also other kind of co mobility's might play into the decision. But a lot of patients really are qualifying for an autologous stem cell transplantation if the patient qualifies. What we usually recommend is about four cycles off autism people in a little bit extra method zone. That's still the standard of care until the best response. Sometimes we give more cycles if we see patients still benefits and we can achieve a deeper response before transplant before collection, actually, because then we kind of have this in V evil perching where we have a cleaner stem cell transplant. We freeze this, give the high dose chemotherapy and then do the autologous stem cell transplant. And after that recommendation is to give it an a little maintenance therapy. In some patients, if they have a high risk situation, we sometimes give a bit more than just learn a little might. Or we if a patient cannot tolerate the Lenin who do, might, we can switch to protest, um, able to other treatments. But this is basically the standard of care that we do, but you can see on the bottom. This is from the NCC and guidelines that a lot of other options in certain circumstances, this might be relevant for the patient. First line treatment in patients that are not eligible for transplant is again the induction with RBD, maybe in a slightly different schedule, and then the Lenin leader might maintenance treatment or what has been approved recently. It's a combination of their automobile, any leader might and dexamethasone until progression. So both options are very good and usually very well tolerated, even in patients that are more frail and are not eligible for stem cell transplant. It's very important to achieve a deeper emission. So that's why we still kind of keep up this idea off the high dose chemotherapy. As you can see here, we can assess nowadays with modern techniques the so called minimal residual disease, which has a sensitivity about 10 to the minus 5 to 10 to the minus six myeloma cells in bone marrow. So Emily Negative has been shown toe go along with a very good prognosis. Oftentimes, even risk factors like such a genetic changes are overcome by this by deeper emission. So if the patient response very well, they have a much better outcome than obviously patients who don't respond very well. And here are new developments, new combinations. It seems like Mauritz better in myeloma, so we for a long time we had this R V D as a triplet. Now some studies show that trouble it is more effective and brings more patients, as you can see on the right to columns into an energy negativity. And this goes along with a better prognosis. And these are combination off Dara to Mom up. As I mentioned in transplant non eligible patients together with coalfields. Me blended leader might indexing methods. Owner Together with autism, Leonard Leader might dexamethasone. Those combinations is cultural. Bloods are not approved, but they are tested in clinical trials, and the show very promising results. Of course, it's more toxic if we need. If we need more more drugs off, use more drugs. Mostly it's him. A geologic toxicities, which hematologist usually can deal with. Some patients show rash on little might. Some patients very rarely show Kartik toxicities off the Kafeel Smith. Unfortunately, still very common side effect is a neuropathy in patients with autism treatment. But those are rather manageable. So I strongly recommend, especially in younger patients, especially in patients with high risk disease, to use a very strong treatment to bring those patients in the deeper mission to improve their prognosis. Since we, as experts in myeloma do Onley myeloma on, are very focused on this, I think it's important that a patient at least once in their career before they start their treatment or when they just started their treatment, see myeloma expert because, as you see, it's very complex to diagnose and also to treat myeloma. So it has been shown that seeing an academic center at least once in the career of a myeloma patient make sense. So we're very open to see those patients and also to manage them together with the colleagues in the community. So it seems to be relevant that the patient is seen in the center for their prognosis and also what eyes even I mentioned basically that my Lomas oftentimes miss because it's it has common symptoms, but it's rather rare. And this is more rare, even the nasty sibling off myeloma, the L, the light chain amyloidosis, which is even more difficult to differentiate because the symptoms are all over the place. So we look for Emily doses in our myeloma patients and also in our gas patients, if they have a weird consolation. Off symptoms are like neuropathy like swelling off the tongue like cardiac insufficiency, together with an Angus on a lot of other symptoms, like bleeding can kind of guide us in the idea, at least to look for Emily doses than we do certain biopsies. And this is something that which should also be treated in the center, or at least diagnosed and then given out toe with a clear recommendation. Based on the knowledge that we have required here with this, I would like to thank you for attention. And I'm hopeful that we get some patients together. If you look a t this and that, we can do the best for our patients in the future. Thank you. Created by
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