(Guest Lecture): October 2023 - Personalizing Therapy for Each Relapsed/Refractory Myeloma Patient

So like maybe going five weekly or a little break here and there. Yeah, I think that we are learning. I think that these therapies are still very early compared to some of the other drugs we have experience with. I know that in the case of toclostomab in particular, there is some data to suggest that for patients who have achieved a very deep disease response, the dosing can be spread out further. I would love to be able to tell a patient that I have a test that I can do on their marrow or on their blood that says, this is how much BCMA expression you have right now. This is how much you need for this drug to work. But I don't have that available at this point. What else? Would MRD testing be kind of a good test to do to help determine or help a patient make that decision along with the doctor to see you? I think it has the potential. I think that in myeloma, MRD testing, I could just sit down. In myeloma, MRD testing is still something that we're learning to use. So does everybody know what that refers to as far as yes? So MRD is an acronym or an abbreviation for minimal residual disease. And there are newer technologic methods of taking a bone marrow sample and figuring out just how much myeloma is still in that sample. So improving upon the pathologist's capability to look at the slide and count cells with their eyes, they're able to take the genetic material from a patient's initial bone marrow biopsy, use that as a kind of signpost, and then look for those signposts, even if they're present in very, very low levels in a sample later on. So we know that it is good to have less disease. It's good to be MRD negative. It's good to stay MRD negative. We don't know when it's important to achieve that MRD negativity. Is it better to get there really fast or is it just as good if you eventually make it down there? We don't know how long someone can be considered MRD negative to be able to start using the cure word. Wouldn't it be cool if we could say that MRD negativity for this many years equals cure in myeloma? We don't know that yet. We also don't know how much residual disease counts, if that makes sense. So if you achieve MRD negativity, that right now means that in a sample that's taken, there is no myeloma cell detectable at a sensitivity down to 10 to the minus 5, according to FDA rules. According to the rules for the company that does a lot of the MRD testing, they can go down to 10 to the minus 6. So that's one in a million or one in 10 million. So if you get down to that level, that's great. But what if you're down to that level and you then start to pop back up again and you're at 11 cells or 15 cells? When do you say that the disease is coming back? That part's really hard. So my answer is yes and no. Yes, I think it could be useful to use MRD testing in that manner. But we don't have enough data yet to say when the switch actually is going to become a critical switch that will make you change your treatment decision. Do you think it's something everyone should have done? Or is it an option? I think it depends. The question of is it an option is an interesting one. There's two main ways to do MRD testing. One of them is with something called next generation sequencing, where they're doing procedures in the lab where they're looking for that specific genetic marker for that individual's myeloma cells. There are some patients whose myeloma cells do not have what's called a trackable sequence to them. So what happens is I have a patient that I'm seeing. I'm going to order a bone neurobiopsy. I know that I want to get MRD testing for them. I ask my team to work with the company that does this test and they can get a hold of the original diagnostic bone neurobiopsy that was done at some point, maybe five years ago. Or something like that. They send that to the lab, which is in Seattle, and they look at that sample and they say, are there trackable sequences that are present in this patient's sample from the past? Can we use those trackable sequences on this future sample? So some people don't have a trackable sequence, and that's just the way their myeloma is. The other way that the MRD is sometimes done is with a specialized type of flow cytometry. And that's done in specific centers. So some areas of the country can do it. Some of them don't have the same capabilities of doing it. So it can be done for many patients. Do you have to have it done? I think it's becoming more important. But as I mentioned, we don't yet know how to use the tools as well as I think we're going to know in the next few years. Can I ask two questions on the mouse? Sure. So one is, when you get your lab results, you just go in for your regular blood drawn on. You get your lab results and it will say, and they're doing, they're looking at your light chains and they're looking at your M-spike. And your M-spike will say, at some point you hope it will say, no previously identified monoclonal antibody is present. At that point, I would think that possibly somebody might want to do an MRD test. But if it's present, then you know you're not MRD negative, right? Well, it's yes and no again. So the MRD test is done on the bone marrow sample. So as you might be aware, there are patients who have myeloma that's active outside of the bone marrow space. So people who have plasma cytomas or they have disease that has come out of the marrow space in association with bone lesions. And it's possible that you could be MRD negative in the bone marrow, but still have active myeloma somewhere else in the body. So that could be a condition where if you have a plasma cytoma that is producing myeloma protein that can be measured, that you would have a measurable light chain abnormality or an M protein, but still have no evidence of disease in the marrow. So that's something to just just kind of keep in mind. So my other question is, so I was always secreting until about a year and a half ago. And all of a sudden, Dr. Cowan told me that it wasn't secreting because of some testing. And then I changed my medicine and it would say that it was we can see it. And then it would say not pretty. And then I had the PET MRI and I had the colonal sequencing for the MR. And everything looks clear. So then I asked myself, am I really not secreting or was it just not showing up because I'm MRD negative? It's hard to know. It's hard to know when the disease changes over time, which I think people unfortunately have to have to live with. Becoming non-secretory is something that often happens after someone has had initial treatment. And as you get to later lines, there are some people who are non-secretory from the beginning, which can be another wrinkle into how we manage things. In newly diagnosed, are you now always doing close-in? Just so you have that baseline already? Yeah, I'm not. And the main reason is because I've had a good experience with the company that does the procedure, being able to get the archive specimens. And so it's been fine. So it's just like one extra layer of complexity on the set of bone marrow orders that I'd rather not trouble people with, if you will, because I know that we can usually get the archive specimen and test it from there. I do think about it a lot, a lot more with the newly diagnosed patients who are going through their initial induction because we're starting to use it, at least I'm starting to ask for it more when we're checking that marrow to decide if it's time to go on to transplant. Because if someone is MRD negative at that point, and maybe they're on the fence about if they want to go on to transplant, that's another conversation about, you know, what is that going to be adding and what do we know about the state of the disease at this point? So I know that some of you at least, oh, yeah, go ahead. Your thoughts on CAR T and race and trans men? I don't know. I don't know. I think that a lot of us were super hopeful that CAR T was going to be a cure. And it's a tool, right? It's a tool that we're learning how to use and we're learning the best time to use it and realizing that that best time might be different for different people. I think it's I think our current structure for how we use transplant with the idea that we want to get a patient their best possible response and then hold them at that best response for as long as we can. That all still holds. That all makes sense. And we're going to be learning whether CAR T is just as good as transplant at achieving that best response. I don't think we're going to know the real answer to that question for years. Those studies that are starting to look at randomizing between CAR and auto for newly diagnosed patients. There's a whole bunch of them coming down the road. We're going to see what they what they have to show. Can we have a stem cell transplant after you have a car? Yes. Yes. And more than one car? That I think we are going to see it, but I don't know exactly when. So I know there was mention about how there are different targets to CAR T that are being developed. I was I was sending an email about one of my my patients to a bunch of colleagues all around the country earlier this week. This patient has had myeloma for a while, has had many, many lines of therapy, has relapsed off of BCMA CAR. Then we gave him tel-catenab so that GPRC51D by specific antibody. So two cell directed therapies in a row. Now disease is active again. And so the question that I sent to my colleagues was A, do you think it's smart or not smart to try to give another cellular type immune therapy again? A third in a row. Like are the rest of his cells going to be able to do it? And then my second question was, should we still be considering using this BCMA target because it's just been a few months since the the CAR T exposure or should we be trying to do something completely different? And so we went with we went with trying to avoid doing the same cellular therapy type mechanism work, trying a different target. And we don't know is the truth. We're just trying to make decisions that make sense for the person in front of us. So my partner Kathy had compression fractures and that led to the initial diagnosis and had production therapy stem cell transplant. Now it's been two or four years since the stem cell transplant, but it hasn't had any scans or MRIs to look back or compare with the baseline of the compression fractures. And the the the later we should never should she be getting regular scans? It's a little it's a little unclear, actually. I know Dr. Banerjee mentioned that he does sometimes do that on an annual basis for patients. I do it for some patients who have had really profound bone disease, like lots and lots of lytic lesions, particularly for patients who are living with a fair amount of chronic pain, because it can be really hard for an individual to know if something's different about their pain when they've been living with it for a long period of time. The other reason that I think it does sometimes make sense to look again is if you were to get a scan like a PET scan, which shows you something in addition to the architecture of the skeleton, the PET probably you guys know this, the PET as the layer of showing us which tissues in the body are very metabolically active. And so some of those are expected to be really metabolically active, like your brain. But some of them you would see brightness in an area of active disease, like an area of your skeleton. And that can be useful to use if the labs seem like they are no longer readable, if someone perhaps is becoming non-secretory or if there's a change in the labs, you don't know whether it's an important change or not important change. Do you think some HMOs just have their certain manual scans? No, they absolutely do. They absolutely do. So when I know you mentioned that you guys were at at OHSU. OHSU's. Okay, but but the OHSU process for scheduling imaging, I warn all of my patients about this because it's frustrating for them. We schedule the scan. They get the date for the scan on the calendar and the current world is that the insurance communicating office, the office that gets the authorization for the scan, they work based on when that appointment is set. So they would seem so silly to me. They work like starting 72 hours before the scheduled appointment to ask the insurance company for the authorization. And as far as I can tell, the only thing it does is cause anxiety for for all of the patients, their family members. They'll be like, what are you talking about? We scheduled this six weeks ago and it's just very hard for people to understand that that is the workflow and that's the cue that was put together. So I get the opportunity to talk to lots of insurance companies, you know, within a relatively short period of time of when the scan is planned. And I generally I can sometimes like talk them into things that they don't want to do. But even if I can't, I try to ask them what would be approved because I'm trying to just get an understanding of what is considered acceptable right now. And the whole body CTs seem to now be on the list of what is approved for many of the different payers. The whole body MRIs are increasingly also on that list. There's some specifics about how it has to be ordered so that the intention is understandable to the insurance company. Kaiser, as you guys know, is a whole nother whole nother world as far as getting those approvals set through. So it may be that your your team is working through that framework and trying to figure it out that way. Yes, please. So that. I know Dr. Cowan mentioned the difference between transplant doctors and non-transplant doctors. I'm a non-transplant doctor, so I don't do them as often as the transplant doctors do. So for patients who are secretory where I think I have a measurable protein, I'll do a bone marrow biopsy when it's going to change what I'm going to do. If I'm pretty sure that someone's disease has become active again and that we've got to make a change in therapy, I don't know that we need to do a bone marrow biopsy for the sake of the test. But if I really want to know is something different about a patient's characteristics, if I'm curious, if I'm underestimating or overestimating their disease burden based on what the labs are showing, then I might do it. And I also don't tend to get the surveillance bone marrow biopsies on anniversaries. I know that some some people really do feel strongly about doing the like one year, two year, three year bone marrow biopsies following following transplant. I don't know that that's universal. So are most of you working with community teams as well as academic teams or how did how did you guys find out about this? Because it's great. It's I've never been to one of these before. It's a really good one. What do you mean by community teams? Well, like I know a fair bunch of you go to the hutch. I didn't know if you go to the hutch as your primary place that you go or whether you go there as your check ins every few months. I'm with the prime group. I don't know. Are some of you in a in a world where you're being co-managed, where you go to the academic center and you also have a community doctor who's making some of the game day decisions about? I'm kind of on the roof. Kaiser is very little. Reaching out to the patient. This is what's available to you. It's been true. Our own research of different organizations and financial assistance and getting on going to the webinars online. OK. But it's been disappointing. Kaiser, they have not reached out to say this is where it is available to you. There are local support groups. We just didn't know about it. This last year or so. And so we're just sort of hearing this. OK, I I ask because my my team, so the nurse coordinator that I work with and the medical assistant who helps me do all of my work, we've started revising the packet that we are giving out to all of our our newly referred patients. We've been talking about what we think is the most important information to include in there. And so, you know, we always give a list of reference sites that we think are reasonable for people to go to because we want I think it's impossible to tell people not to research their disease. And so it'd be better to just say, you know, start with these places where there's good, well vetted information. So we always give that kind of information. We give some information about general, you know, how the academic medical center is structured so people can understand when they call on the phone, where's their phone call going and who are they going to be talking to. We try to give a little bit of information about financial assistance programs. But I guess I just haven't been clear how how how do people normally find out about those sorts of things? Like there's a lot of resources through the LLS and through other charitable organizations. People find it just by happenstance or they go looking on their own. Yeah, we didn't even have to reach out to them for help. And you learn about it. You know, I just Google it. I was actually telling a couple of nurses when I went in for my injection, they didn't even know about it. And they said, what is that? I said, that's the best thing ever. You know, yeah, some of the staff, they don't even aren't aware of this. Yeah, I mean, I think the myeloma community is really, really remarkable because there's a lot of different organizations and health. He's one of them that provide a lot of really high quality information to patients and caregivers. And they're they're very open about wanting people to talk to each other and wanting people to feel comfortable asking questions and learning what's what's available. How much do you think that's going to help them? I think it's going to help them to be able to talk to each other and be able to be able to be able to be able to be able to talk to each other. How much do you guys talk about money with your health care teams? I've been very lucky. I haven't talked to them about money at all. They've just found grants. They found this. They said, OK, here's what your bill is going to be this month. That's great. It is very reasonable. And did they know that you would be someone who would appreciate a grant or did they just presume that anyone would appreciate a grant? When you talk about rebel myth, they assume anybody would appreciate your grants. And I actually ended up with one grant for rebel myth and another grant for some of my other drugs. Yeah, but I didn't do anything. Yeah, because it's getting to be that time of year where the MA that that helps me who's I mean, he's an angel. He starts sending out the messages around now saying, dear patient, you have this grant and this grant. I am working on the renewals. And part of that is him wanting to do it so that they don't start the process and muck it up for him and make it more difficult. Where are you where are you treated? Where are you treated? In Olympia. I'm just curious because at the Hodge, I know when you first go there, they set you up with a pharmacist and social worker and a social worker will sit down with you and talk about what options and connect you to resources. Beyond that, I'm not sure what else they do. But in terms of letting people know about things, so here in Seattle, some of you may know there's something called the My Loma Fighters. And that's just a group of people that get together monthly. And now it's all assuming we have speakers every month and they're always someone that's medical like a lot of people from the medical community here. But one of the things that they've done is they ask members who don't get treated at the Hodge that are treated in their communities to send the names of their doctors. And then they have a flyer that they send out to the doctors to say the My Loma group exists if people want to do it. And that could be something that Health Tree, that would be a way for Health Tree to get the word out to people. Because they've done that at Swedish and Hodge. Those doctors know to tell people about My Loma Fighters, but they may not know about Health Tree. No, that's a really good suggestion. That's a great point. I'm in that little area where you kind of just give me everything because I'm not being treated there. So I don't usually see the social worker or the nutritionist or anything unless I request. Like if I was a patient of theirs, I think I would have more of those services automatically given to me. And if you can be said, there's not even a social worker. And they don't know. And when you talk to me about My Loma, it's just a small sliver of their practice that they may not even be aware of things that would be helpful. Yeah, I think that's actually very common. And I think it's just part of the reality of how health care is structured right now. There's just a lot of staffing shortages and there's a lot of turnover. And it's very hard, I think, for patients and their caregivers to try to know who their primary points of contact are. I do think that's another one of the great benefits of this kind of organization that you can. It sounds like you can kind of message people in various groups and to just get a gut check. Does this make sense? What's happening? Or should I be trying to get more information in some other kind of kind of forum or some other kind of setting? And I know health care is actively going to communities and taking regions at a time and just sending our materials to those community practices, you know, just so that we can put things in people's hands. Yeah, because once you have something, you see what provides you all you need is that one initial point and then you can find so much more. Yeah. How much do you guys look into clinical trials? Do you independently look or do you wait for someone to bring it up to you? Or how has that been? The other question I was going to ask you. Oh, sure. So we don't get a lot of information on clinical trials. The neurologist, you know, will talk to her. No, no, there's nothing really available. But I'm wondering, since we're close to OHSU, there must be some clinical trials going on there. So Kaiser's really it's a closed system. It's a difficult financial system to work within. I can give you a couple different perspectives that the doctor perspective is that we email each other and we know who each other are. And if one of the Kaiser docs has questions and is curious about a trial, then they email us. And we have absolutely enrolled some Kaiser patients on to clinical trials at OHSU. It takes, you know, another level of massaging the system to make it possible, but it can usually be done. And what I think has to happen is that the Kaiser team has to agree that this is a treatment that's different, that makes sense and is appropriate for this patient. And they kind of be let out. The patient side of it, though, is hard. So you mentioned that you had transplant at OHSU a couple of years ago. There are some trials in the post transplant setting where we as physicians are often wondering whether our Kaiser transplant patients could be eligible for them. And for example, we have one that that we've just opened last week, which is doing post transplant consolidation therapy in patients who are MRD positive after after the procedure. So doing set amounts of novel therapies to try to convert those patients to MRD negativity. And it feels like it would be a great opportunity for Kaiser patients who might want to to participate in that. And we're beginning the legwork to try to figure out how we can connect with the Kaiser Kaiser team. So for those of you who I don't know how it's set up in Seattle, in Portland, if a patient is receiving their myeloma treatment through Kaiser, the contract that Kaiser has for transplant is with OHSU. So the patients see an OHSU transplant physician. They become an OHSU patient until day 90 after transplant. Thirty, maybe for a chunk of time, like through the transplant period and then afterwards. And then you kind of get a return to Kaiser packet is my is my understanding of how things go. Yeah. And I think it's similar for Carti at this point. I'm not I'm not sure of the time time windows there. I have another question. I think it's really important to get second opinions. I did ask the hematologist about that. Oh, I really totally agree. But like I wanted to ask Dana Farber saying, oh, ask us any question. Well, my mom, they're they wanted twenty five hundred dollars for me to ask a question. I thought, I don't think I want to spend that much money. So we have to have Rob's niece whose husband knows somebody who works at CTVA phone. Now, like, well, through the emails, we got that. I got my answer. No cost. But what is a protocol to go is is the fee of that sort from Dana Farber? Is that would be normal? I mean, you know, Kaiser doesn't have a I know our position is not like multiple high level discussions. Yeah, I've seen that some of the second opinions from Dana Farber come in kind of two styles. There's the the opinion that people seem to get, which I think is entirely based on record review. And then what comes back is like a essay. It's nice, but it's like a report on how they are reading the patient's history and data and recommendations based on that. So that I think might be the fee based one. I'm not not positive. The other kind is when you would go and present yourself to the clinic that you want to be seen in. And you would get, I believe, an insurance paid for second opinion. So Kaiser's different, but outside of Kaiser, it can be it could be something that's arranged. So at City of Hope, they actually have a Kaiser kind of center that they do bone marrow transplant and CAR T with the Kaiser patients. So that's maybe another reason why it was easier to get information back from them. It sounds like you might have gone through the unofficial channels. You did have my back channels. No, nobody knew. I just said we have a plan and I can't. I want a second. And it was about the Revlimid going down to five milligrams because of neutropenia. And I wanted to hear, what do you think? Because I'm doing better. Why can't we go back up to Canada? That's the dose. But the question, the bottom line was, stand by if you're doing fine. Don't go back up to the town. And I said, OK, well, I'll go with that. That's what I've done. So but no, they didn't know I was a Kaiser patient. We didn't share that. But they were very liberal in their thoughts of, you know, asking if you have anything else get back with us. And I just thought, well, you know, I'm I'm in the positive response. I don't call it. I don't call it so much that we're in a a non-state here. I just call it positive response for two years. But, you know, maybe it's going to be coming down the road to prepare ourselves. What are we going to do then? Because I know it's going to be sitting there going, OK, here's our standard procedure for what you're going through based on your labs. And it's like, OK, I want another opinion or maybe a third. And it's like sort of freaks me out a little bit of going, am I going to have to go through the same thing? Or who can I go to that really has special? You know, I find out you're an OHSU. I mean, we've already dealt with Dr. Masaraz. It was a character. And and then Fred Fred Hutch Medical Center gets real great reviews, too. And these seem like good options. And then the other piece is that many of us chat with each other and we just send messages around and we gather opinions and we don't know the answer because medicine, there's often not a right answer or wrong answer. It's just different shades of the color and trying to figure out what's best for this person based on what might be available to them is sometimes. Well, I think that's what we're gathering. So I'm going to different conferences and webinars is that the one answer is not absolute. There's some real great areas and it's like, well, why don't we try this or do this and whatever? And I think I, you know, working with Kaiser, they're workable. It's not like they're just putting up a wall and saying no, but they don't always give me the answer. I want to hear, I guess. Yes. So anyways, I appreciate hearing the communication from maybe you know, which is you with Fred Hutch and stuff on the West Coast. But, you know, just when you're going, well, I know our physician is not a multiple myeloma specialist. And it just sort of like, is she reading up on everything? So I sort of wizard every three months. Are you aware of this? And she sort of looking at me because we only do videos. I honestly read every three months and it's pretty fine with us. But she I think she sort of realized that we're up to date a little bit more than the average patient just because we're supporting each other and really trying to get what's out there. If I didn't even know anything, my background is nursing. I had no idea what multiple myeloma was two and a half years ago. This is amazing. Yeah. The support for this condition. I think it's incredible in a good way. Like, I think it's really, really good. You know, one of the things you were trans. So you were in the new building. I know you came down at the waterfront. Yes. If you believe it, one of the biggest complaints that I hear from patients that I've taken care of for a while is that even though the building is pretty and modern, it's too broken up and they miss actually being able to sit in the waiting room with a bunch of other people and get to know each other. And, you know, we used to we used to be on top of the hill near near where the main hospital was in this very historic building that will collapse when the when the earthquake comes. And he said it was one open room, which had basically armchairs around around the edges of it. And people actually really miss that they got to make friends with with each other and they would realize that they were on a similar schedule. And then they would realize that maybe they all came up from Corvallis together or something, something like that. So I think the community is something that's very underappreciated in a lot of the formalized health care. I'm surprised that they have support. This is what I was complaining to our physician about. I'm with Providence. Right. So Providence has the monthly support. It's not my alone specific. I'm the only five-star patient. So you know, you have to, you have to. Oh, it's time to go. You.