(Guest Lecture): September 2023 - Setting Up Your Expectations For Having Myeloma

Today, we're going to be talking about setting up your expectations for having myeloma. This is the newly diagnosed group. Some of you might be newly diagnosed, others might be further along in your journey, but know of others who are newly diagnosed. There's patients here, there's caregivers here. Whoever you are, you've decided to come to this meeting because you want a little bit more exposure in terms of setting up expectations for having myeloma. Now, Dr. Chen is going to talk to us today about how he educates his newly diagnosed patients. He's going to share with us different things that can help those who have been diagnosed last week or maybe two years ago. There's so much to learn in myeloma that whoever you are, no matter where you are in your journey, we're happy to have you here today. Not only is the disease incredibly complex itself, but the treatments that come with it and the side effects that come with it and just the heavy mental burden of having a disease such as myeloma can be really heavy. And so we are again grateful that you've chosen to be here today or to listen to the recording if you're listening to the recording. And with that being said, I'll introduce Dr. Chen to you and we can get started. Jason Chen is a hematology staff physician at the Ann Arbor VA Medical Center and a clinical assistant professor at the University of Michigan with a focus on hematologic malignancies such as multiple myeloma. His ongoing efforts include expanding the hematology research portfolio at the Ann Arbor VA and improving cancer care across the VA system. Dr. Chen received his MD degree from the University of Rochester, completed his internal medicine residency at Thomas Jefferson University Hospital and hematology oncology fellowship at Michigan Medicine in 2021. Dr. Chen, thank you for being here today and we're excited to hear from you. The time is now yours. Thanks Audrey and I'd like to thank Health Tree for the kind invitation to speak with you guys today. Give me, just give me a moment. I will pull up my PowerPoint slides. Audrey, just confirming that this is showing up okay on your end. Yeah, it looks great. Thank you. Awesome, great. Well, thanks again for the very kind introduction and really excited to be here today speaking, talking to you guys about newly diagnosed myeloma and setting up expectations. And once again, I'm Dr. Chen, Jason Chen and one of the hematologists here at the Ann Arbor VA and the University of Michigan and I am focused on myeloma. So very happy to talk about my experiences, my patients and also hoping to learn from you as well. I think a lot of what I do on a daily basis and in my research life is directly because of the patients that I've talked to and worked with over the years. So just to start off, I have no relevant disclosures. I do have to mention the views and opinions expressed here solely my own and do not reflect the opinions of the Department of Veterans Affairs or the University of Michigan where I work. So for today's agenda, I'll start off by just presenting an example patient case to set the stage for our other discussions. I'll talk a little bit about staging and survival rates in myeloma, then move on to talking about the symptoms of myeloma which many of you are probably unfortunately familiar with, as well as the side effects of the different kinds of myeloma treatment. And once again, we'll be focusing about newly diagnosed myeloma treatments, not necessarily some of the newer treatments that have been approved for relapse or refractory myeloma. And then finally, we'll summarize three key points before opening up the seminar to questions. So start off with the patient case. This is the one that is very similar to the patients that I see here at the Ann Arbor VA. Ms. Lang is a 72-year-old woman who is being seen by her primary doctor for unexplained left arm pain. Dr. Smith notices severe pain when touching Ms. Lang's arm and so he orders an x-ray to look for a fracture as well as some blood tests. Dr. Smith gets the results back of the x-ray and it shows that Ms. Lang has a left humeral fracture or fractured the left arm. And then her blood tests also show anemia, which is low red blood cell counts, as well as kidney injury, which is indicated by a high serum creatinine. And these are new and unexpected for someone like Ms. Lang who is otherwise healthy. Dr. Smith is concerned about blood cancer like multiple myeloma and refers Ms. Lang to a hematologist. Ms. Lang sees a hematologist, Dr. Lee, in the clinic and Dr. Lee orders a bone marrow biopsy. The report comes back and mentions 30% plasma cells consistent with a plasma cell neoplasm. And Dr. Lee also orders a PET scan, which the report mentions multiple FDG-Avid lytic lesions with a left humeral fracture. Dr. Lee meets with Ms. Lang and her family to talk about the results at a clinic visit and he says that unfortunately the tests do show that you have a blood cancer called multiple myeloma and Dr. Lee recommends treatment with a chemotherapy regimen called RVD. He talks about RVD as well as alternatives, the side effects of these different drugs, overall prognosis for her diagnosis of newly diagnosed myeloma and also mentions a stem cell transplant referral as well. As you can probably imagine, this is a very exhausting day for Ms. Lang and her family, but she agrees to the plan and schedules follow with Dr. Lee in clinic. Some questions that I hope to answer during this talk, what should Ms. Lang expect now? And just thinking about your own journey, does Ms. Lang's journey sound familiar to you? So just a brief overview of myeloma. So multiple myeloma is the second most common blood cancer after lymphoma and of interest to my patients here at the VA, it is associated with agent orange exposure and so that is considered a service-connected condition and I would encourage anyone on this talk if you're a veteran and this could be a concern to bring it up with your primary doctor as soon as you can so you can get the benefits that you deserve. Myeloma is caused by a normal white blood cells in the bone marrow called plasma cells and when they become mutated and abnormal, they're called myeloma cells and we can detect these, we can detect the consequences of these cells because they secrete a type of protein called a monoclonal protein or M protein and this can be found on blood tests or sometimes in urine tests as well. And myeloma, while generally not considered curable, the treatments that we have for newly diagnosed and relapsed myeloma are very effective and can lead to longer survival rates and I'd like to mention, one of many times during this talk, is that the landscape of myeloma treatment is not standing still and there's always ongoing research so what I mentioned today may be different than what we do in the future in the sense that what we do in the future is much safer and much more effective than what we have today. In terms of staging for myeloma, myeloma is thought of staged in different ways than other solid tumors like for instance, colon cancer or lung cancer and breast cancer. We don't really use the traditional stage one, two, three, four or necessarily use the terms metastatic or localized cancer. Instead, we use a staging system called the Revised International Staging System where our cancer is not necessarily and this is a score that takes into account some different blood tests like albumin, beta-2 microglobulin and LDH as well as genetic mutations that we see on a patient's bone marrow biopsy and it gives us a score of one, two or three. And this is helpful mainly for assessing risk. So does a patient have higher risk disease or higher risk of myeloma? Does a patient have higher risk disease or higher risk myeloma which may not respond as well to treatments or may become resistant to treatments relatively quickly compared to those that do not have higher risk disease? So an RISS score of three, so that's the highest score, is considered high risk. Another thing that the RISS score looks at but also myeloma experts look at are genetic mutations. The term that we use is cytogenetics and we're looking for certain translocations or certain mutations, deletions, additions, rearrangements that may predict a more aggressive lymphoma. There is something called gene expression profile and it is mentioned a lot. We don't necessarily use that here at the ANA-BREV-A but it is something that other centers do use to, again, assess the risk of progression or how high of a risk a patient has. And then finally, we look at clinical markers of aggressive disease. So PCL stands for plasma cell leukemia. That's when these myeloma cells aren't just in the bone marrow in the bones but they're actually out in the blood and we can see that similar to if someone had leukemia. And then EMD stands for extra medullary disease. So those are basically myeloma tumors outside of the bone. So different than what we considered a standard myeloma. And these are all ways to assess if someone has higher risk disease or lower risk disease. And I will also mention that the research is ongoing on how we can better define higher and lower risk. So again, what I say today may be different than what we're talking about in five or 10 years. In terms of survival, I think there's a lot of ways to look at it and it depends a lot on the risk category. So if someone's higher risk versus lower risk, the types of drugs that a patient goes on, the study that you look at when you review the literature, a patient's age, other medical issues like if they have heart disease or diabetes, as well as transplant eligibility. So if someone is considered a transplant or a candidate for stem cell transplant. And I generally quote from my patients, those that do not have high risk disease, what I would call standard risk, I would say at least five years and in some studies, 10 or more years. So in general, the prognosis is relatively good compared to some other cancers. For patients with high risk disease, this also depends a lot on the individual patient characteristics and the study that you're looking at when you look for these numbers. But I say generally less than five years, maybe closer to two to three years. And just for some reference, in the past when high risk myeloma was defined, the overall survival was less than two years and we made a lot of significant progress since then. So in terms of the side effects of myeloma, us as clinicians think about mnemonic, which is CRAB, C-R-A-B, and that helps us remember the different types of things that myeloma can cause. So the C stands for calcium levels that are too high. The R stands for renal injury or kidney injury. The A stands for anemia or low blood counts. And the B stands for bone lesions, which are usually lytic lesions. So those are basically holes in the bones and I've listed the different side effects that these can cause over on the right-hand side. So some common combinations that we use for newly diagnosed myeloma. We usually think about three drugs at least and there are some four drug combinations as well. So we think about RVD, which is one of the most studied combinations, which consists of three drugs, Fortezumib, Lenalidomide, and dexamethasone. I put the brand name next to those as well. We use these three drugs, I put the brand name next to those as well. We also think about DRD or DERRD, which contains DERRTumab, Lenalidomide, and dexamethasone. There's another combination that's often used when patients are in the hospital called CyberD or BCD. And that contains cyclophosphamide, Fortezumib, and dexamethasone. And then there is emerging evidence about use of four drugs rather than three. And the combination that we use here in the United States primarily is something called DERRRVD or DRVD. And that contains DERRTumab, Fortezumib, Lenalidomide, and dexamethasone. Now, these are the ones that are most commonly used. Sometimes patients are started on just two drugs, a doublet regimen, but I think the standard of care for most patients should be at least three or four drugs. So in terms of the side effects for treatment, I'll go over the side effects of interest for each specific drug, and then I'll go over some highlights from each combination just to put things into perspective. So Lenalidomide or Revlimid is a pill that's usually taken something like two weeks on, one week off, or three weeks on, one week off. The main side effects of this that I see, the biggest one is a rash. It can be itchy, it can be very diffuse all over the body. People can sometimes have diarrhea as well related to Revlimid. Low blood counts as well. Revlimid can cause low red blood cell count, platelets, and neutrophils. And then this drug can also increase your risk of clots. So anyone that's on this drug, Revlimid, needs to be on either an aspirin or even a low dose blood thinner to prevent those clots. The next drug is Fortezumib, and the brand name is Velcade. And this one, the main side effects are mostly related to the gut, so things like nausea and diarrhea, which can usually be controlled with medications. It can cause a rash as well. The other big side effect is neuropathy. So tingling numbness in the fingers or toes. Sometimes when patients describe it as walking on cobblestones, so an odd sensation for sure, or even unfortunately sometimes falls or gait imbalance. And that's really important when we think about our patients because they're often older and may have issues like diabetes, which can predispose them to having neuropathy already. Fortezumib can also cause low blood counts. It can also increase the risk of infections, particularly shingles. So if you know some of the shingles, you know that's very uncomfortable, it's very painful, and the pain can sometimes last longer than when the rash disappears from the shingles. And so we always start patients on something like acyclovir or valacyclovir to prevent shingles infections if they're on a medication like this. Dexamethasone is a steroid. And so if you know friends or family on steroids, you know they can have significant side effects. So swelling, especially in the legs, it can raise blood pressures or blood sugars. So that again, is something to consider in our patients that have diabetes or are high blood pressure issues or heart disease. A lot of my patients report that they get very revved up. They get a little boost of energy from the dexamethasone, which can be a good thing for some, but it also can be a little bit too much for others. And they can have issues with anxiety and insomnia. So I usually recommend that patients take it first thing in the morning. And also to be honest with their hematologist about reducing the dose or spacing out the doses if needed. And over time, this dexamethasone can also thin the skin. So a lot of my patients do report that it's easier for their skin to get cut and also bruising as well. Last two drugs I'll talk about is daratumumab or Darzelex is the brand name. This is usually given either intravenously in the vein or sub-Q like an under the skin injection. Here at the anaerobic VA, we use the sub-Q or the under the skin injection version. This one is generally doesn't have as many side effects. I think the biggest one is something called an infusion reaction. This is similar to like an allergic reaction where you might get fevers, unexplained chills, some shortness of breath. Those are generally mild. And usually patients that receive this, if there's no major issues after the first two doses, I don't expect any issues for the remainder of the doses for the remainder of their treatment plan. Something that comes up that patients may not necessarily feel, but definitely comes up when they're trying to get care with other providers is issues with blood typing. This is an antibody drug and it actually affects the way that the blood bank checks a patient's blood to find a blood unit for transfusion. So if for some reason, someone that was getting this drug needed a blood transfusion, they would get their blood sent down for something called typing, where they try to find a blood unit that matches with the patient's blood type. And this antibody can affect that. And so I always tell patients, before they set start on this drug, I always have them get their blood typed in screen just to make sure that they need blood. We know what the data is ahead of time before adding this drug on. And if they need a transfusion at some point during their treatment with this deritumab that they let their provider know that they're getting this drug so that the Red Cross or the blood bank can appropriately deal with this kind of lab error, essentially. And then finally, cyclophosphamide or Cytoxan is a traditional chemotherapy. It's usually given either as an IV or pills. Here at the NRBV, we usually give it as pills. I think the biggest side effect for this drug is probably nausea. And that's really more related to the fact that people are usually taking quite a few pills of this Cytoxan to get the dose. So something like eight to 10 pills, and that's a lot. And so people can definitely get nausea from that. It can also cause some fatigue and low blood counts, but generally well-tolerated other than having to take all the pills. So putting it all together, since that was a lot of information and a lot of drugs with different side effects, really all of these regimens will have dexamethasone in it. So you'll always get some sort of side effects related to steroids. So the swelling, the high sugar, the insomnia at night, and some degree of fatigue. All of these combinations will have some GI side effects. So things like nausea, maybe diarrhea, and a rash as well. And then there's always an increased risk of low blood counts and infections because you're suppressing the immune system with these drugs. So for the different combinations, things that I'll look out for, for RVD, which is what I use most commonly here at the AntibraVA, I mentioned the risk of a rash, GI issues, so nausea and diarrhea, as well as neuropathy. For DERA-RD or DRD, I do mention the rash as well, as well as infusion reactions. For CyberD, I do mention the rash, nausea, and neuropathy risk. And then for DERA-RD, I mention the rash, the GI issues, nausea, diarrhea, neuropathy, and infusion reactions. Some other things that are also often given to myeloma patients in addition to these chemotherapy regimens are supportive care drugs. So things to primarily support bone health. As you remember, the B, the C, the D, as you remember, the B in that crab mnemonic is bone lesions or lytic lesions. So people's bones, unfortunately, are fragile and they're on higher risk for fractures when they have myeloma. And so the two drugs we think about starting are either X-Giva or dinosumab or Zometa, which is zoledronic acid. X-Giva is a shot under the skin that's usually given once a month. Zometa is an intravenous drug that's usually given either once a month or once every three months. Both generally well-tolerated, but they both have a risk of jaw osteonecrosis or essentially issues with healing of the jaw, especially if someone has a lot of dental disease or if they have an oral surgery plan. So for my patients here, I always recommend a good, obviously a good exam of the mouth and to see a dentist to make sure that there aren't any procedures like a tooth that needs to be removed or an abscess or infection of the mouth that needs to be treated before I start either dinosumab or zoledronic acid. The side effects of dinosumab, it can cause low calcium levels. So that's something that has to be monitored closely. And there is a risk of rebound bone weakness in the sense that if you stop this drug, which is given once a month, if you stop this drug abruptly, there's a chance that your bone will actually become more fragile when you stop the drug. And so for those that need to stop this dinosumab, I recommend at least one dose of the drug below, the zoledronic acid to really lock in those bone benefits that you've already received. The zoledronic acid hangs around longer, it lasts in the bone longer. So I generally prefer that one more, and it doesn't have that risk of rebound bone weakness that the dinosumab has. Other things that you might've discussed with your oncologist about is something called palliative radiation with a radiation oncologist. And this is often used if someone has a painful bone lesion, like something in their hip that's causing hip pain or something in their arm causing arm pain. And generally the side effects are pretty minimal because the doses of radiation that are used for this indication, for this reason, are much less than the doses of radiation used for say treatment of lung cancer or breast cancer or other cancers. There are a lot of other medications that patients are put on to help with pain related to their myeloma, neuropathy, things like gabapentin or Lyrica, nausea medications, anti-diarrhea medications. I won't go over those today, I know there's a lot of resources on the HealthTreat website. What about stem cell transplant? And I think at the initial discussion, when a hematologist is talking to a patient about myeloma and the treatment, sometimes the discussion about stem cell transplant gets a little bit lost because it's a very overwhelming time and it's hard to absorb that much information. But it is something that I still recommend for my patients, at least to be considered. Stem cell transplant, we don't do that here at the Antibirth VA, so we refer out for that. And basically a patient would need to be referred to a specialized center that can do these transplants. And usually there are quite a few visits and tests that need to be done to make sure that someone is fit enough or healthy enough to get a stem cell transplant. Those are things like evaluating heart function or evaluating lung function, evaluating social supports and mental health. Those are things that we think about. If someone is deemed a candidate for stem cell transplant, then they usually have an appointment to have their stem cells collected. They're usually given some sort of injections or drugs to boost stem cell production. And nowadays those stem cells are collected from a patient via basically an extended blood transfusion or phoresis instead of what has usually been done in the past, which is actually harvesting stem cells from the bulimera. That's not usually done anymore. Once those stem cells are collected, they're basically frozen for storage later for the actual transplant. At the bone marrow transplant center. And on the day of transplants, patients usually come into the center. They get IV chemotherapy, which is usually melphalan. And after the day after, usually those stem cells that were frozen and collected from earlier are thawed. And the stem cell transplant itself is more like a stem cell infusion, like a transfusion where those stem cells are basically given through an IV just like a blood transfusion over extended period of time. And then afterwards, most patients are admitted to the hospital for monitoring because as you imagine, when someone's stem cells or when someone's original bulimera is being suppressed by that chemotherapy they got earlier, their blood counts can drop dangerously low and they can have severe side effects from that chemo. And it takes some times for those infused stem cells to find their way back into the marrow and regenerate the blood counts and regenerate the marrow. And so patients need to be monitored pretty closely for things like infections, bleeding or other complications. So going back to our patient case, as you remember, Ms. Lang was diagnosed with multiple myeloma. She had a humoral or arm fracture and she had low blood counts, anemia, as well as kidney injury. And she was started on a chemotherapy regimen called RVD. She received six cycles of RVD and achieves a CR or complete response and is deemed a transplant candidate. So she undergoes a stem cell transplant, does well and recovers and is started on post-transplant maintenance with Revlimid or lenalidomide. So some take-home points, multiple myeloma can cause high calcium levels, anemia, kidney injury and bone damage. And I use the mnemonic crab to remember that, abbreviation crab to remember that. The survival for most patients is in the span of many years and is improving on a year-to-year basis because of new treatments that are coming out. The main side effects or treatment include rash, GI issues like nausea, diarrhea, neuropathy, so numbness, tingling in the fingers or toes, as well as low blood counts. And with that, I'd like to thank you all for your time. Thank you again to Health Tree for the kind invitation and I will open things up for questions and I'll stop sharing as well. Thank you. Awesome, thank you, Dr. Chen, that was great. I appreciated the different points that you went over. I especially wanted to touch on how you were saying that the longevity of myeloma patients is increasing. And I would say, the quality of life as well is improving of these patients, as you mentioned. And I think one of the important points that I just wanted to drive home, because I know this can be obviously an overwhelming topic for myeloma patients to hear. And I'm not gonna say anything that necessarily will make it easier, but there are several studies that show that getting your care from a myeloma specialist or having a myeloma specialist on your team, regardless of risk, increases the longevity of your life and the quality of your life by significant amounts. And so for the audience that may not know, a specialist is someone who is involved in research because this disease is so complicated. And as you said, more medications are being approved all the time. And so you need somebody that's staying on the forefront of things and somebody that sees generally more than 100 patients per year. So talk to your physician and make sure that they fit that criteria because you're gonna want somebody who understands the ins and outs of myeloma. So anyway, just wanted to put that point out there because I know that it can be overwhelming. I do appreciate you bringing it up because it is a common question and something that people want to know, especially in this stage, but it can be overwhelming. So I just wanted to encourage the use of a myeloma specialist. I wanna add to that and just say that one thing I didn't mention in terms of treatment option is a clinical trial. And so that offers us, usually for the newly diagnosed myeloma stage, and there are certainly more trials for relapse or factory myeloma. So we won't go over that today, of course, but for the newly diagnosed myeloma trials, usually they offer, it's a comparison between the standard of care, for instance, like RBD. And for instance, like the one of the trials looking at RBD versus DERA RBD. So it's either a standard of care or potentially a new standard of care. And so that offers patients the opportunity, one, to contribute to our knowledge about myeloma, like what is better for patients, and also the opportunity to try something new in terms of something that might actually help them live longer or live better. And as you're pointing out, having a myeloma specialist is probably the only way to get access to that because they may not be accessible to someone that doesn't have that expertise or interest. Yeah, very well said, thank you. I see a couple of questions here. I invite all of your questions. If you wanna click on that Q&A icon that you see near the bottom of your screen and submit your question, you can make it anonymous if you would like, but we appreciate all questions. So we'll start with Michael's asking, can RISS or the risk status basically of your disease change after a relapse? Yeah, great question, Michael. We don't usually repeat the RISS, I-S-S, sorry, staging when someone relapses. It's really used for initial diagnosis. What we often do, at least what I do, is I'll repeat a bone marrow biopsy to look to see if some of the genetic mutations, if there are any additional ones, for instance, that we would consider higher risk, and that may help us inform how aggressive or maybe how much less aggressive we should be with treatment in the relapse stage. And sometimes there's ongoing trials that are targeting specific mutations that you need to get that repeat bone marrow, essentially, to get that reassessment. So I hope that answers your question. Very well said. And I'll mention too that it's not a guarantee that it will change. The longer you have myeloma, the more likely it is that you'll see different clones and different variations within your myeloma. So kind of the catch-22 of living one. Okay, good question here. Having had shingle shots, does that limit the likelihood of getting shingles? Yeah, another great question. And a lot of, I'm glad you got the shingle shot, first of all, and it's a question that comes up a lot. Yes, to some degree, when people are started on treatments for myeloma, it does suppress their immune system, including plasma cells, which again, are the cells that actually make the antibodies that help you fight off infections. And so the effectiveness of that shingle shot, unfortunately, will be diminished by the treatment and by the myeloma. And certainly if you go through a stem cell transplant, where essentially cleaning out your marrow, you have to start from baby shots all over again. So that shingle shots you got before will not offer pretty much any protection after a stem cell transplant, unless you get revaccinated. Yeah, shingles can be an interesting one. And you'll want to make sure if possible, what is it called? What is it called when you like test for levels of, it starts with a T. The titer? Yeah, can you do a titer for shingles? I think you can. I don't routinely do that, because I start all my patients on something like acyclovir to prevent shingles. Sometimes for other vaccinations after a transplant, the transplant center will want to check titers to see if someone's immune system has recovered to the point that they can generate a vaccine response. And that's a good sign. Awesome, thank you. Carl asks the question here. It's a good one and it's very frequently asked. It has to do with the fact that high-risk smoldering myeloma patients are either only offered Revlimid plus dexamethasone or a clinical trial in order to receive treatment. Now, Carl, this is an excellent question. It could be a webinar all of its own. I personally could talk about it for hours. But Dr. Chen, in summary, why is it that high-risk smoldering or smoldering myeloma treatments in general are limited? And what do you see being done in that field to change that? Yeah, it's a great question and it's still an evolving field. Smoldering myeloma, what's considered high-risk and who needs treatment? I think it has a lot to do with the comfort level of providers. Myeloma providers even just because that data is relatively new and evolving. And I think there's probably a well-intentioned but deeply rooted mindset from myeloma physicians that myeloma is considered incurable. And so at all stages of treatment, we think about quality of life, trying to make sure someone is living as well as possible with myeloma. And for some folks with high-risk myeloma, they are not necessarily having any symptoms related to their myeloma. That's the definition, right? They're not having high calcium levels, kidney failure, low blood counts or bone lesions. And so putting someone on treatment would subject them to side effects. And one of the long-term side effects of R, the Revlimid is risk of secondary cancers. And so thinking about that, sometimes it's hard for us to make decision of, do we wanna subject someone to that risk when they're not actually having any symptoms when they see you in clinic versus watching them closely if they progress to active myeloma and have symptoms, in which case the benefits of treatment outweigh the risk. So more to follow, and you're not the only one asking this question. I hope to have an answer the next few years. Yeah, definitely. We just had a Boston, we had a round table in Boston, which is just an in-person myeloma education event for those unfamiliar. And Dana-Farber Cancer Institute is doing a lot of research in the precursor myeloma field. And that's one of the things that they discussed during the round table was, why are we not treating? And they were talking about the deep research that they're doing to identify through genome sequencing and mass spectrometry and some crazy, really high tech stuff to identify which smoldering patients, even within the high risk category, are most likely to progress to active myeloma and then treating them perhaps through some immunotherapy. I know they have quite a few trials actually, because I know Carl's lament is, there aren't a lot of medical centers in the United States that are hosting these smoldering trials, which is true. But if you find a specific institute that is very interested in precursor myeloma, you'll see lots of trials there. So it's difficult, not everybody lives in Boston. And as you said, Dr. Chen, it's a question that not only Carl is asking, but so many others. And I'm sure we're sure to see results within the next five years, definitely. Sally asks a good question, but it's a loaded question. Is outcome better with or without stem cell transplant? Yes, and this is also a great question. And personally, a lot of my patients actually are not candidates because of age or other medical problems. But in general, I think most myeloma experts would say that stem cell transplant can deepen remission or deepen response and prolong progression free survival or prolong the period that someone does not have active disease, but does not necessarily improve overall survival, which is how long someone is actually gonna live. And I think there are also some studies that are looking at whether someone should get a transplant upfront versus transplant later in their disease course. And there may not be much of a difference in terms of overall survival, but I think most of the data still shows that getting it upfront transplant will delay progression of your myeloma in the hopefully distant future. So I still recommend it because I think people are generally their healthiest at the initial stage of myeloma before they're sort of unfortunately beat down by myeloma and treatments. And so I still like to recommend it because I think whatever period we can get where they're not having active myeloma, where they're just on things like maintenance, revlimid, a pill a day without much side effects, I consider that valuable time than waiting for later. And so I still recommend it upfront but I know there's a lot of ongoing research in this as well. So just like the previous question, I hope for the next, hopefully less than five years we'll have more information about what is actually truly best for patients. I agree. I'm gonna have you briefly explain what CAR T therapy is for people that are not familiar with it because I think your answer might have even been a little different if we were talking about two years ago, three years ago when the first CAR T therapy was, when was it approved? 2020, 2021? I can't even remember anymore. But that's a lot of the research that's being done are these immunotherapies which use a patient's immune system to help identify and fight myeloma versus a chemotherapy drug that's trying to just wipe out all cells and hope that only the healthy ones grow back. That was an oversimplification everyone. So don't quote me on that. But Dr. Chen, do you mind briefly explaining what a CAR T cell therapy is and then how there's a trial right now that's comparing head to head CAR T therapy versus a stem cell transplant in an upfront setting? Yeah. So I don't have too many details about that specific trial but CAR T therapy, it's an acronym for chimeric antigen receptor T cell therapy. And essentially these are taking the patient's own cells, T cells, which are a type of immune cells that actually helps fight off infections and actually cancers as well and re-engineering them in order to specifically target myeloma or markers on myeloma cells. So the approved ones right now target a surface protein called BCMA or B cell maturation antigen. And there's two of them that are approved, at least to my knowledge, which are brand names of BCMA and CAR-VICTE. And they're not quite, they're not used or indicated in upfront setting, but they are, I would say very effective in the relapse setting. If you can get evaluated for that and you're a patient with relapse disease, so maybe not in this audience, I would highly recommend looking into that further. It may not unfortunately be where you're being treated but it may be hopefully somewhere nearby, like for us down the street is University of Michigan and they do that. So yeah, so more to follow, but definitely very promising in the relapse refractory myeloma space. Yes, and as I mentioned, there's clinical trials going on to see if they can bring it to the upfront setting. And then if so, trials comparing the two to see, okay, which one is better or more efficacious. I think we're living in a time, an exciting time. I mean, nobody wants to be diagnosed with myeloma, but myeloma has seen such amazing progress over the past 20 years. I was talking to a doctor last night who's been in the myeloma field for over 20 years and also works in other cancers as well, blood cancers, and says myeloma has had the most success, we'll call it, within the past 20 years, which is so exciting. So again, nobody wants to be diagnosed with myeloma but I just wanna give some hope to the audience out there that being diagnosed with myeloma is no longer a death sentence because there is such amazing treatments out there and specialists out there and clinical trials out there of people who are really working hard to improve quality of life and improve longevity. So, and improve, like create a cure for multiple myeloma. So pretty exciting stuff. Absolutely, absolutely. Michael's wondering how often do you do a bone marrow biopsy? Yeah, I usually do a bone marrow biopsy initial diagnosis. Sometimes the, either myself or the stem cell transplant center will request a bone marrow biopsy before and or after transplant. If the patient, if someone undergoes stem cell transplant and then usually I relapse, I do a bone marrow biopsy again to assess someone's risk. And also there's any mutations that we can target either with clinical trials or other drugs. Awesome, thank you. Steve says, many of the drugs affect red cell counts. I'm on revelative maintenance after a stem cell transplant. My O2 saturation or oxygen saturation dropped into the mid 80s on a recent hike. Is there something other than dietary iron that can help short of transfusion? That's the great question. I would say, I would definitely talk to your doctor about potentially getting your blood checked. I'm not sure if your blood levels are really low, like you had anemia, in which case the transfusion will help with that. The other thing that I would worry about and something you should definitely talk to your oncologist about is whether there's concern for a clot in the lung, such as a pulmonary embolism that can be causing your oxygen levels to be low. Revlimid or lenalidomide can increase your risk for clots. So, we use medications to prevent that, but those are not a hundred percent and people can definitely still get clots even on best attempts to prevent that. So I'd be worried about blood counts, which a transfusion might help with. And then also if there's a clot somewhere. Thank you. Okay, this is a great question. When it comes to survival, when do you start counting? So, Brigida was smoldering multiple myeloma, but I mean, when we're talking about it increases overall survival, when does that start? Yeah, the study probably just, when you're initially diagnosed and enrolled on a trial, that's when they consider, when they talk about progression for your overall survival. Yeah, and that would be with active multiple myeloma usually, is that correct? Yeah, I think she was asking about smoldering. So those are specific to the trials, but usually it's from the time of diagnosis and enrollment on a trial. Yeah, yeah, with the, yes. Because they just, after like 15 or 20, like a long time, 15 or 20 years, it took for them to finally finish that Revlimid and dexamethasone trial and how it didn't necessarily improve overall survival. So. Yeah. I have to jog my memory, but there's definitely two big studies. One out of Spain, I think that might've showed an overall survival benefit. But these smolder myeloma can smolder for a long time. And so it takes a long time for basically scientists to get enough data to say, this is definitely better than the other or worse than the other. And the same when you think about overall survival in myeloma, this is disease. Again, people are living 10 plus years. So you're gonna take at least 10 or more years to get the results from the study. And so that will just come with time, but hopefully that's soon. Yeah, yeah. Well, thank you, Dr. Chen for your input. We are gonna be ending a little bit earlier, but I don't know if anyone's gonna complain about that. So I'll give you just time for any closing comments that you have, and then we'll finish up for today. But thank you again for being here and for your shared time and knowledge. Yeah, great questions by the panel and glad to be here. Thanks again to Health Tree for the invitation. Multi myeloma is, it's a devastating disease, just like any other cancer. But like Audrey was saying, I really am delayed to be able to provide some hope for patients and their families because the treatments are much better. The treatments are generally have less side effects or much better tolerated than some other chemotherapies. Like when someone's reflecting on their experience with say breast cancer or brain cancer or colon cancer. And I think it's really very rewarding to be able to help someone through that journey, wherever it may go and try to improve quality of life and give someone the best life possible with myeloma. Yeah, well, thank you for all you do. Yeah, thank you. We'll let him go and then to my audience, I'll keep you for just a little bit longer as we have some outro announcements. For those of you who are unaware, we have our Health Tree 2.0 launch coming, and that's gonna be on October 23rd. You can join this virtual event that's hosted by a couple myeloma patients actually, that needs to be updated. We encourage patients and caregivers to host your own satellite launch parties. This is such an exciting event where we're able to talk to you about our new and improved model, how we are going to help accelerate a myeloma cure and how you can be a part of that. Talk to you about specific goals that we as an organization have and how you can volunteer and help us with those goals that will benefit all of us in the myeloma community. And then we're also gonna be talking about as well, our expansion into other blood cancers and how if you have loved ones with other blood cancers outside of multiple myeloma, we can bring the same benefits and programs and success that we've seen within the Health Tree Foundation to other people with other blood cancers as well. So make sure you register for that event. It's a virtual event that you're welcome to attend. And these slides as well as Dr. Chen's slides will be sent to everyone. So you'll have access to register for that. Upcoming events that we have on next Tuesday is our Black Myeloma Health Chapter and we're gonna be talking about advocacy. On our Thursday, September 28th meeting, it's our amyloidosis chapter and we're gonna be talking about the role of stem cell transplant. The link to sign up for any of those events and even more events I didn't mention is found at the bottom of the slide and will be included in our follow-up email. Another thank you to our sponsors, Adaptive Amgen, Janssen, Abbby, GSK, Bristol-Meyer Squibb and Regeneron. And thank you to each of you for taking the time to be here. I hope you have a great rest of your day. Take care, everyone. Thank you.