(Guest Lecture): Myeloma Imaging | MCRT Webcast: Myeloma Imaging

[Music] it's really pleasure to be here again with the myeloma crowd even in these weird times as jenny said um i'm very uh fortunate to have connected with the myeloma crowd uh quite some time ago and i'm very happy to be part of this because this is really always for me a great experience because it teaches me what the real questions of my patients are obviously my patients ask me in my clinic but you know there's often times not really a lot of time for such questions and i'm um i always like these interactions during those meetings the q and a's and i learn what's really interesting for people and i think my patients benefit from that as well and since you pitched the idea with talking about our exercise study coming from the imaging and you will see what i will mention later i was really intrigued in what can we do to help the bones to regrow and using the neuroimaging techniques taught us that bones of myeloma patients can regrow it's not a guarantee and we still don't know what we can really do we know of course that bisphosphonates and our treatments are working well for that but we think that even exercise work out for our patients in a safe environment is is good and so we do that at the moment at roswell park in a limited capacity because of covet unfortunately but we are working on together with myeloma crowd and health tree to get this out in the field and um if you can enroll in the health tree that is very helpful then we will give you information about this and we want to do an exercise study with the health tree coming to milo imaging and it's difficult to stop talking about imaging for me because i have done that for over 20 years now and it's i think it's very intriguing what we what we can learn from imaging um i know it's expensive but i think it gives us so much more uh information than a lot of other things that we do so it's it's a very important very informative tool the uh topics that um jenny and greg gave me where uh here you as you can see why imaging techniques are changing treatment i try to answer that to a certain degree uh what are the new guidelines for imaging and um what in mri why is mri still relevant uh we can see myeloma and we can identify targets so these are the topics i want to kind of give the introduction to but then i think the most important part is the interaction the q a later on where i can answer or dr langer and i myself can answer questions that you might have about imaging um what the first very important thing i want to mention is that imaging does not only show changes in the bones you know that the bone marrow and i guess all of you have a painful experience with bone marrow biopsy and i'm always bragging that i had four bone marrow biopsies on myself for research um so i know how bone marrow biopsy feels but that's actually where we where we really know that the bone marrow is very important that the bone marrow is inside the bone because we have to put a needle in through the bone to get into the bone marrow and that's also important for imaging because um we can have techniques that show more the bone or better the bone and others show better the bone marrow as you know myeloma takes place in the bone marrow but the effects and the symptoms one of the major symptoms are those australia deletions destruction of the bone oftentimes leading to fractures and i fear that most of you have experience with that so the bone is the the area where the symptoms take place so the disease is in the bone marrow while the symptoms are more in the bone um oftentimes when i give and other colleagues give talks about treatments you know those timelines that we have really a huge uh development of new treatments within recent years which is really amazing but you can also see in the inner line here that a lot of new imaging techniques have been developed and i just see there's one double have to change that the dc mri but um a lot of techniques have been introduced beyond just x-ray in multiple myeloma to use and to identify changes in the bone marrow and in the bone so why are imaging techniques changing the treatment i think a very important part is that we can detect the disease earlier as jenny already mentioned here on the left side is a minimal infiltration this is actually looks like normal bone marrow of a healthy adult the lumbar spine it's so-called t1-weighted imaging of mri magnetic resonance imaging and you can see the intervertebral discs and i'm not sure i hope i can use my my pointer here are the intervertebral discs are darker or hyper intense compared to the bone marrow because the older we get the more fatty bone marrow we have if fatty bone marrow is replaced by a malignant disease like for example multiple myeloma you can see this diffuse infiltration you see here the vertebral bodies have almost the same grayscale as the intervertebral disc so this is a diffuse infiltration and we see this in about 60 percent of myeloma patients but sometimes myeloma patients also can have so-called focal lesions and that's something that we talk a lot about nowadays you can see those dark spots and those we actually did a study and i will talk about that later a little bit more um we we found that those are actually small tumors of myeloma cells growing in the bone marrow and we call them focal lesions and they have to become more and more important in recent years so you see here on the background uh the focal lesion on the background and almost normal looking bone marrow but some patients also have the background of the diffuse infiltration with a focal lesion on top of which which is of course not very easy easily seen because the background is darker but these are the patterns that we see when we do mri in multiple myeloma patients so it's about thirty percent chest diffuse thirty percent just focal and third percent mix that's why i said sixty percent have focal lesion sixty percent f diffuse so there's an overlap with this mixed pattern and about ten percent have this normal looking bone marrow why is it relevant i mentioned that the disease actually takes place in the bone marrow as you can see here this is the mri again and again you see a different patient you see small spots of bone marrow infiltration but if you see on the right side the ct the computer tomography you see those bones look intact there's no lytic lesion in the bones you see here this grayscale is very homogeneous so you see changes this is the same patient at the same time one time with mri one time with ct and you can see here the changes are visible in the mri but not yet in the ct meaning there are already myeloma lesions like small tumors but no change in the bone so no osteolytic lesion yet this is very important to differentiate bone marrow from bone um but of course we don't want to wait until there are austerity lesions and that's the reason why those focal lesions in the mri especially in patients with smoldering multiple myeloma have become more and more important and we looked into a significant number of myeloma patients with smoldering myeloma back in the day with his old definition of smoldering myeloma and we found that if a patient has more than one of those focal lesions their progression into symptomatic myeloma meaning every step down is a patient progressing into symptomatic myeloma they have a much higher risk to progress into symptomatic myeloma if they have those focal lesions in mri so we can kind of to a certain degree predict when the patient will progress based on those focal lesions interestingly enough it's not only the focal lesions themselves it's also very important if those focal lesions are growing or if they are staying the same we did uh in a similar patient group we did uh um several mris over the course of the disease of a smoldering myeloma patient and at that time the patients were not treated just because of the focal lesion so what is very important if those focal lesions are there and they don't change over time then there is no high risk of progression here it's kind of the opposite than the the other graph that you saw you see every step up is a patient progressing and here in these patients who have changes sometimes but no um no dynamic no growth of these lesions or not more lesions over time they don't have a high risk to progress so one lesion or two lesions that are not growing are not very important or not very dangerous but when those lesions are growing when they so show kind of a cancerous characteristic then they those patients had a very high risk to progress actually a 16-fold higher risk than these other patients so focal lesions that are there and that are growing at or if new uh new focal lesions appear that is an important uh prognostic factor and then we should definitely treat the ph patient and we found that this was actually correlated with the protein level but not it was still an independent marker and how did those patients progress that's from the same analysis that we did and it might be very small sorry very small for you to see but those small red bees that are in here where all patients progressing with a bone disease so those patients we we did the crab criteria and the b the bone disease was the major reason of those patients who are progressing with focal lesions they develop bone disease later on that's why we think that the mri focal lesions predict the uh progression of of bone lesions why is it important to predict it early several groups and especially dr landgren's group niha cordy from his group published last year that patients that are treated with um smoldering multiple myeloma get treatment high-risk patients who have high-risk features they benefit very much from their treatment and a lot of those patients um became mrd negative uh by next generation sequencing and had a really excellent outcome and what also was uh important is um the mrd as you know is as you might know uh is done from a bone marrow biopsy and the bone marrow biopsy is just a small area in the bone we usually do it on the pelvis or very rarely in the sternum um and so we only get information from this single location and as you might expect if a focal lesion is there we will detect something if it's not there then we might miss it and we might have and have actually patients that are emerging negative in the bone marrow and the pelvis but if you do a ct guided and imaging guided biopsy of an australia deletion there is still some active disease so this is very important that we combine the imaging with the mrd assessment that also led all those those experiences led to new guidelines of the international myeloma working group i mentioned that a higher sensitivity is important and i really really advocate for uh using ct instead of x-ray and the colleagues who were involved in these guidelines um also agree here is a patient who had pelvic pain and outside they did an x-ray and they said no that looks fine as you can see here it looks like on the other side so it looks like it's a healthy pelvis but then we did a ct and it's unbelievable but here this darker gray blob here is unfortunately a plasma cell tumor we did a biopsy and it was confirmed that it is multiple myeloma destroying the bone here and growing out of the bone this is really a patient a few days apart x-ray and ct so you can see ct is much more sensitive this led to the uh we did a comparative study in about 25 were negative in x-ray and positive in ct so we have a much higher sensitivity to detect osteolytic lesions and this in the new guidelines is the recommendation for example for amgas patients we do the ct instead of the x-ray uh initially we don't do it in low-risk mgas and in intermediate risk and gas but in high-risk angus occur according to certain markers um will lead to a low dose city or should lead to lodo city if that is inconclusive then the mri is more sensitive but you might know mri is more expensive takes longer so the screening and this is an international guideline so we have to also of course take care of of countries outside of the u.s who might not have access to all of those techniques so we decided to first do the whole uh whole body lotto city if your uh provider has access to an mri or whole body mri then is that's of course important if this is positive then we would do a pet because in the pad we see if those lesions are real if they are active so the pet city would lead to treatment indication if possible if positive sorry is positive if everything is negative then it's just an ambus in smoldering myeloma very similar screening with whole body lodo ct if inconclusive whole body mri if that's negative we recommend a yearly mri in smoldering because of those focal lesions that can appear over time and that then can develop into osteolytic lesions if the mri is positive um and it's less than two so meaning one focal lesion then we would do it every six to every uh every six months and also do cts to make sure that there are no no destructions of the bone if there are more than two focal lesions that would lead again according to the new guidelines to a multiple myeloma treatment if the patient already has a symptomatic myeloma or a suspected symptomatic myeloma we recommend low-dose ct or if available pet ct if that is negative and mri because of this high sensitivity if that is also negative we call it smoldering myeloma because if there are no other reasons of course there could be anemia hypoglycemia that would also qualify a patient to be symptomatic but if that if the mri is positive again two more two or more focal lesions would lead to treatment a positive fdg or ct um would also lead to a treatment because bone destruction is a reason to treat why is mri still relevant because we want to also identify targets of the treatment and here's something that really i always think when colleagues tell me oh i'd rather do x-ray because i um it's cheaper it's faster but why would we do something that is inferior so like the mole optometrist who says this is enough if we can see this i think we have to be more sensitive and more aware and um as as i mentioned we have these focal lesions what happens to them after treatment we saw that if a patient gets treatment a lot of those focal lesions disappear and we did that in mri so mri is still good and we see that we have a lot of oftentimes unfortunately a lot of focal lesions left the downside of the mri is that it doesn't differentiate between active disease and and disease that has basically healed but is still there you can see if you if you look closely here on the right on the left side here that's the right because we look from the front uh on the right you see this gray scale here and after treatment you see how it shrank the problem is um here in this t2 weighted imaging it's white and white or hyperintense means that it is cystic so it's a fluid accumulation not active myeloma anymore so mri can help with treatment monitoring but pet ct is actually the the treatment of the diagnostic of choice a newer technique and you might hear of that from other colleagues and we have also started using this the so-called diffusion-weighted mri which helps us to identify those lesions you can see here which which with much more contrast here this is the patient after treatment and you can see it's much less of those lesions and much less um and much smaller lesions so we see with a very sensitive technique to follow those focal lesions over time and we also want to learn more and that's kind of the targeting effect this is a myeloma patient where we did a biopsy of such an osteolytic lesion and it sounds a little bit barbaric i agree and we started that in germany and you know we are very rough uh people there no but um this is under local uh anesthesia and conscious sedation not not intubated but something to to be sleepy and it works very well and i really we have done over 90 patients now and no patient really complained about it our radiologists are so good in what they're doing they do that for solid tumors all the time so the patients really say this sedation helps them they don't really recognize or get anything uh from it and we had no complications whatsoever so now we are doing further workup and you can see here this is even a very small oscillating lesion and i checked we got plasma cells out of it you can see here the needle goes in and it exactly exactly hits the focal lesion that has been here and at the moment we are doing research on those cells that we get out of there and we found first uh differences actually from a regular bone marrow biopsy which would be actually in this area because as you can see here there's not much between the outside and the the bones that's why we do those bone marrow biopsies here but compared to those osteolytic lesions we see some changes in those cells so they are not always the same cells and with this i would like to end um it was just kind of a very short overview about those topics and i'm more than happy to discuss further later on in our q a i thank my amazing team at roswell and the people from the university university of heidelberg german cancer research center in heidelberg and dr landgren who really taught me a lot about myeloma and i'm really looking forward to hearing him talk now thank you very much [Music]