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    • Myeloma Crowd Radio Episodes
    • Sep 12, 2019

    Myeloma Crowd Radio: Creating A New Myeloma Center of Excellence in Austin, Texas with William Matsui, MD

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William Matsui, MD

Dell Medical School LIVESTRONG Cancer Institutes 
Interview Date: August 20, 2019

Thanks to our episode sponsor

Summary

Creating a new multiple myeloma center from scratch is a challenge, but one that Dr. William Matsui has successfully accomplished with the new myeloma center at the Austin, Texas Dell Medical School LIVESTRONG Cancer Institutes. Dr. Matsui shares what it takes to create a research lab and clinical practice for multiple myeloma in a new city. He explains how different types of research can be combined from an existing center of academic excellence – building relationships between basic researchers and those who are bringing research into clinical practice. Dr. Matsui shares how the Dell School of Medicine approaches patient care – helping the whole patient with everything that is needed such as providing treatment, emotional support, financial resources or other types of assistance in a holistic way. Dr. Matsui also describes his research to identify and target myeloma stem cells, or the cells that could be causing relapse. This show highlights the need for a myeloma specialist on your care team. Regardless of where you live, adding a myeloma specialist on your team is the single most important thing patients can do for their best outcomes. 

Dr. Matsui on Myeloma Crowd Radio

Full Transcript

Jenny: Welcome to today’s episode of Myeloma Crowd Radio, a show that connects patients with myeloma researchers. I’m your host, Jenny Ahlstrom. We’d like to thank our episode sponsor, Celgene, for their support of Myeloma Crowd Radio.

Now, before we get started with today’s show, I’d like to give just a quick update on the software tool we created called HealthTree. We now have over 4,400 patients who are using the HealthTree, and you might notice the new design.

In HealthTree, you can track your myeloma in a single place, your genetics, your labs, your prior lines of therapy, and then you can see treatment options that are personally relevant at every stage of your myeloma that you can then discuss with your doctor. You can find clinical trials you’re eligible to join which personalizes your list from about 450 open studies to about 10 to 20 that you’re actually eligible to join. You can find financial help. You can answer researcher survey questions to advance insight and a potential cure.

Soon you’ll be able to connect with myeloma patients who have similar genetic features to you. We’re also building a doctor and researcher portal to help your doctor see your HealthTree profile in a single place, and this will help them provide you with a second opinion if you’d like to go do that as well. So it’s very important that you enter all your information and keep it updated. Once it’s there, before your doctor sees your profile, we’ll be validating it with you.

There are three ways to get help if you need help doing that. In HealthTree, there’s a Support button in the bottom-right screen. You can ask questions in that live chat window. You can also click the Help button and find a 1-800 number you can call. We also have a program called the Myeloma Coach. You can find a coach who can help you walk through HealthTree, and they can help you with other aspects of having myeloma as well. So especially if you’re newly diagnosed, you may want to use that program called Myeloma Coach. You can find that on myelomacoach.org.

HealthTree is also now accessible through your phone. We continue to improve the design, and we’re excited to be adding more features that are coming over time.

Now on to today’s show, creating a myeloma research center is no easy task, we’ve really reiterated the value of the myeloma specialists over the course of this entire program. Dr. William Matsui, formerly of Johns Hopkins, has taken on that challenge to create a myeloma lab, a research center, and a clinical practice at the new Dell Medical School LIVESTRONG Cancer Institutes.

So welcome, Dr. Matsui. Thank you for joining us.

Dr. Matsui: Thank you so much for having me.

Jenny: Let me give you a brief introduction for you before we get started.

Dr. William Matsui is Deputy Director of the LIVESTRONG Cancer Institutes at the Dell Medical School of the University of Texas at Austin. He is Director of the Hematologic Malignancies Program, Vice Chair of Research in the Department of Oncology and Professor of Oncology. Dr. Matsui was formerly the Director of the Multiple Myeloma Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, and was Co-Director of the Division of Hematologic Malignancies at Johns Hopkins.

Dr. Matsui is also a member of the LIVESTRONG Cancer Institutes Executive Committee and many other committees at the Dell Medical School. Dr. Matsui received the Scholar in Clinical Research Award from the Leukemia and Lymphoma Society and the Kimmel Foundation Scholar Award at the Sidney Kimmel Foundation for Cancer Research.

He has been awarded many teaching awards and early in his career, receiving the ASCO Young Investigator Award. He teaches about cancer stem cells at the University of Texas and is deeply involved in mentoring students that are PhD students, medical students, residents, fellows, and students in postdoctoral training programs. He’s received many grants on the role of stem cells and has registered four patents around this topic. We’ll talk about that more in this show because these are early precursor myeloma cells potentially. He is also Associate Editor for the Hematology Journal, Immunology and Immunogenic Insights, and the Journal of Medicine as well as an ad hoc reviewer of really a very long list of publications.

Dr. Matsui, we are thrilled that you are with us today. We’re fascinated to know about this new program that you created. This is no easy feat.

Dr. Matsui: No, it is definitely not easy. I think that it is one of those things where you sort of say, oh, it’d be so nice to have this and this and that. One way to do that would be to just do it yourself. That’s an idea to go into it, and then when you’re actually there trying to do it, you say to yourself, oh, my God, I can’t believe that I don’t have this and that and the other thing. I need to just do it myself.

So it is been a great experience up to this point. It’s been, I think, the biggest challenge of my career personally, but I think that at the same time, it’s been this incredibly fulfilling, and it’s just been a wonderful thing getting started.

Jenny: Well, you came from Johns Hopkins, which has a really deep myeloma practice, and you were Director over that myeloma program. So when you think about things you might want to do, it’s not just simply that you’re moving to a new facility and becoming a myeloma specialist of a different center. You’re actually creating a new clinical practice, a new laboratory, a new research center, and all of that that comes with it.

Dr. Matsui: Right. One thing about the school that I think is very unique is that it’s a totally new medical school. It’s been around for about five years It’s right on the corner of the main University of Texas at Austin campus which is a huge university. There are many medical schools that have been started more recently, but part of it is that they’re not necessarily affiliated with a giant university. So this, I thought, was a great opportunity because it’s not like everything is new. There’s this great academic institution here, but the medicine part of it was new. So it wasn’t starting entirely from scratch. It’s more like there were things here, but they just had to be geared towards health and medicine. I thought that that was a really great place to start from.

Jenny: Awesome. Well, how do you go about creating such a center really from the ground up?

Dr. Matsui: So I think that there are two ways to do it. One way is to say, okay, I have a pad of paper and I have a pencil. I’m going to list all of the things that I think are important in a center. So I’m going to list clinical services. I’m going to list a clinical research program. I think there should be a basic program. You can sort of try to be an architect of doing it that way. The other way to do it is to say, okay, I’m here and what are the greatest needs right now? Go and take care of those. And then once I start taking care of those, as other things start to percolate, I’m going to try to address those.

So I think that really the differences between the two approaches are one is you’re planning for the long run, and then the other is just saying, look, there’s stuff that needs to be done now, so how do I go about doing it? I think that it’s really, in the end, it’s kind of like a balance of the two things. So coming from a place like Hopkins and knowing other myeloma people who have great programs, I think you know sort of what the components of a good program are. I think that at the same time, you want to work towards those things, but you got to do it in a fashion that’s like being aware and responsive to the situation that you’re in.

So I have ideas about where we want to be in five or 10 years. I think that that is a little bit of a different approach than sort of saying, look, today, what do I need to do to try to get myself there? because I can’t just sit here and just keep planning. I need to actually do something. So it’s been odd to have a balance of that, and that is a little bit different than at Hopkins where it was kind of like, well, here’s the problem that’s come up and so you have to deal with that problem. And then here’s another problem that comes up, and so you have to deal with that problem.

So everything is sort of established, and you’re trying to make sure that all the trains are running on time. That’s really the biggest part of the job at Hopkins. Whereas here, it’s more of where do we get the trains and where are the stations and how do we arrange that? In that way, I know the components that are important, and I try not to get anxious about not having them right now. But at the same time, I need to figure out a plan to work towards each of those goals over a month to years.

Jenny: I would think that environment would be really a nice way to innovate because when you have to say, well, why do we have the train coming from this direction, it lets you reevaluate everything.

Dr. Matsui: For sure. I think that that was one of the biggest draws in coming and looking at the place. I think that the school being new, what it what it wants to do is it wants to be unique. You can be unique like at Hopkins by being around forever, or you could be unique being new by trying to do things differently. I think that here, there’s a big emphasis on value-based care. We can talk about that. There’s a big emphasis on trying to tie the basic science that’s going on in the main university over to the medical school and have it be an applied thing. So I think that it’s really a couple of features that are pretty unique to this place that I didn’t really have the opportunity to do at Hopkins.

Jenny: I think one of the unique things too about you specifically is also just your quest for curative type strategies in myeloma. I think sometimes there’s a difference between the application of medical practice and then the searching for this thing we all want, which is a cure.

Dr. Matsui: Right That is doing research and then taking care of patients is really the same balance of planning on something for the long run versus the short term. For sure patients come and they’re sick, and you need to take care of them right away. You need to use the tools that you have at hand that you know work. I think that, at the same time, our job in academic medicine is to try to make things better. I don’t think that my desire to try to cure myeloma is different than any other myeloma specialists around. If you said, look, we’re going to put you out of business, I would say, great, I’m totally fine with that. But I think that how you go about it and addressing it, for sure there are differences of opinions and different ways of doing it. People are good at some things, and other people are good at other things.

One thing about myeloma that’s great is that even though I’m here, I’m in a new place, I think people have been very supportive in the community. I still feel very much a part of the fabric of myeloma and myeloma care even though right now I’m like the only myeloma person here.

Jenny: Well, I think the whole myeloma community, all the researchers throughout the United States, seems to be a very nice, congenial community. Everyone works very well together and likes to collaborate. I don’t know, it’s just something I noticed.

Dr. Matsui: Yes, I think it is. I think that there are, like any sort of group of people, there are different personalities in it. But people are polite, and I think people are willing to listen. For sure, I think that the strides that have been made in taking care of patients with myeloma, that has been dramatically facilitated and accelerated by people working together. No one person is going to be able to get all of those treatments up and running and figure out how we can best use them. It really takes a big group of individuals. I think that the myeloma field has done great.

Jenny: Yes, I agree. Well, what is unique about the Dell School of Medicine and its approach to treating patients? We shared an article and you had mentioned a holistic view of the patients. So whether it’s that or other things, that would be great for you to share.

Dr. Matsui: I think that that’s the biggest thing. When the health enterprise was designed here at UT Austin, at the Dell Medical School, one of the foundations of it was in this area of value-based care. So one of the things about value-based care is when most people hear that, like when I heard that for the first time, I thought it was completely an economic thing, what the cost of care was and how do you get the most out of the medical system for the least amount of money. That, ultimately, is one benefit of value-based care. But really, the way that it’s thought about here at Dell Med is that you’re really addressing the needs of individual patients based upon what they want and what they need.

It may be that every single patient has a different goal for what they want out of their therapy. I think that it’s really kind of figure that out and addressing that provides value. One way to do that is to think more about patients rather than just what is their M spike doing, or what are their light chains doing, or what’s the regimen that they’re on. I think that I’m really good at that. I’m really good at taking care of myeloma. If you said, look, I have this patient with 4;14 and they’re newly diagnosed, what would you treat them with? Would you do a transplant? I can go through that pretty easily.

I think that the issues that I faced at Hopkins were that I could talk to patients about that. But if they had other issues, like it was difficult for them to get back and forth to the clinic or if getting treatment meant that they were going to lose their job or they had to explain their diagnosis to their family, especially I think it’s difficult when you have young myeloma patients who have very young kids, how do you talk to them about their disease and what about their nutritional status and exercise and spiritual wellbeing and all of these things.

So at Hopkins, we could do the medical part really, really well as an individual physician, I could do that with my patients, but it was hard to do the other things. The reason why is I’m not trained to do the other things. You don’t want me managing your checkbook because that’s not what I do the best. I think that one thing is can we provide care to the entire patient up front? At Hopkins, if these issues came up that were outside of their strict medical care, then that would be something where I would make a referral. I would make a referral to a nutritionist or a social worker or a counselor or something like that, and then they would go see that person, and then I might be able to piece it all together.

So here at the school, the way that our clinic is set up is that we, as a team, see the patient from the very outset. So if I have a new patient, patient comes in, I will see them, I’ll talk to them about their myeloma, but then I’ll have a bunch of other people see them so that when people come, it’s a really long first visit because they might see a social worker, a psychiatrist, a nutritionist, a fertility specialist, if that’s something that’s important. All of those people are in the clinic, and so we triage the patient and figure out what exactly the patient needs, and then whatever needs are there, that person is going to help take care of the patient. So I provide medical care, but I am not taking care of all of those other issues where I have no training and capacity to do that.

So I think that in the end, the patients feel like it’s not just dealing with their cancer diagnosis. I think that that’s really important because like in myeloma, patients are typically on chronic therapy that lasts many, many years, and it can be impactful. It’s a chronic disease for many people. We’re trained to go in, see a patient and say, okay, well, you have cancer. So we’re going to do this and then we’re done. I think that now that patients are chronically on treatment, it becomes a different situation where you have to deal with all of these things. It’s not like you can put your life on hold for a couple of months to get treatment or to get a transplant or something. It’s really like it affects you over a long period of time, and it affects the people around you. So can we do something for those individuals earlier in a preemptive way instead of waiting till something happens, and then we have to address it?

So that, I think, has been this incredibly satisfying way to take care of patients. It’s totally different than the way we did it at Hopkins. It’s not that we didn’t take good care of patients at Hopkins, but I think that here the burden, not the burden, but all the responsibility to take care of the patient is not on me because there are other people in the clinic. So I think in that way, it’s been great. I think patients really love it. I think for most patients, it’s something that they’ve never ever experienced, like those who are coming from other practices. That has been the best part about working here is that sort of innovation, I think, is important.

I think in the end, it does become an economic argument because people who I think just feel better about being able to do the things that they want to do and have goals that are aligned, I think it’s less wasteful on the medical system. So you’re doing things before things happen. I think that that’s important. So I think in the end, it does probably save some money. But I think in the end, it’s really much more satisfying for a patient especially when they have something stressful like cancer.

Jenny: This is huge because when my brother-in-law was going through his AML, the fifth floor wasn’t talking to the fourth floor at the Cancer Research Institute. It was very frustrating for everybody. So it’s smoothing that out. I think you might need a new name for it, maybe like integrative care or something like that. So when you first said that phrase “value-based care” what comes to mind is about the economics, because you hear about all these new things that are coming out.

Dr. Matsui: Right. So I think that “value” is really is it valuable to the patient? Not is it valuable to the health economy? That part of it, I think, is making people feel better. Less stressed out is always helpful.

Jenny: It’s fantastic. It affects everything. Everything is so integrated to the patient, and things are not well integrated when they come to the clinic typically. So that’s a fabulous way of doing it.

Well, let’s talk a little bit about the types of research that you’re able to do. Maybe you want to describe the difference between basic research and translational research as you talk about the types of research that you’re able to do.

Dr. Matsui: So I think that in a medical center like this, I think that there are really, I would say, four or five different types of research that one can do. I think that what we do traditionally in cancer is probably three or four different types. The basic part, I think, is the easiest part to understand and that’s like you take very, very, very elementary or elemental ideas that are really, really basic ideas about molecules and about how cells work. You just study them to try to figure out how does the system work? I think that the goal is to figure out how the system works.

I think that when you do, obviously, clinical research, it’s really like how do we set up experiments, the experiments of clinical trials? How are we trying to move the field forward by testing certain things and then seeing if they clinically improve things so then that becomes the new standard? Translational research is somewhere in the middle. I think that you can have translational research that takes place in a lab, and there’s translational research that can take place in the clinic. Most of the time, it bridges both things.

As an example, let’s say that patients with myeloma tend to relapse and one idea is that if you can prevent relapse, then patients should do better. So what do we know about relapse? Is there a way where we can study it and then better understand it?

I think that if I want to study relapse, that’s a clinically derived question. You can try to take that, and then they’ll try to set up a system in the lab where you can test it.

And then on the other side, so in that scenario, all of the questions that you’re asking are not really studying how does this molecule interact with this molecule? It’s more how do we take this clinical question and break it down so that we can study it quickly in the lab? And then if you take that information and now part of it is can you come up with either strategies to treat people or ideas about how to better split people into different categories that make sense prognostically or try to figure out what therapy is going to work for which patient? All of those things are trying to use the ideas that are generated in the lab, and they’ll apply them back to the clinic.

So really, the translational part is the part that I do. We have a lab. The lab studies a bunch of different things. But really all the questions that we ask are grounded in real scenarios that happen in myeloma or there’s this weird thing that happens in leukemia. So how do we make sense of that by trying to do some work in the lab? And then how do we get those ideas back and try them in the clinic?

At Hopkins, the clinical part was very strong because it’s been established for a long time. Here, the basic part of it is very, very strong because it’s a big research university, but the research has not necessarily been geared as much as possible towards health and medicine and disease. So part of my job here is to say, look, you basic researchers are doing this stuff and have these great ideas and concepts. What my job should be is to try to help you take those ideas and turn them into something that’s useful in clinical medicine.

So that’s part of what we’re doing now. That is an entirely people thing. I’m not a basic research expert, but I have to talk to someone in a way that they can understand what I’m saying, and I can understand what they’re saying, and come to some agreement about working together and have some goals that are aligned. And then I think that that’s how you get it off the ground. I think that that’s an organic way to build a program. The more people you get involved, the more things you work together on, at some point, there’s a critical mass where there are a lot of ideas that come out of that synergy.

Really here at Dell, a lot of the first part of being here was really just going and meeting with as many people as I could to figure out what they did. Did they seem like they wanted to collaborate and work together? That’s the first phase. I think right now, we’re just starting to do things together with people and really get that going. But that’s the way that we’re doing it here. I think that if someone said, well, what I’m going to do, I’m going to give you $500 million and build you a building and you can recruit all the people you want, that would be a different way to do it and it’ not a bad way to do it. So if somebody wants to give us $500 million to do that, we’d be more than happy to take it and build a myeloma institute. But like I said, I think the grassroots way of doing it now, I’ve really enjoyed because it’s a lot of fascinating ideas that people have, that they just haven’t thought about them in a way that may be applicable to myeloma or maybe applicable to other cancers.

Jenny: Yes, that’s interesting, because this is a continuum of research, right? You discover something interesting about how a cell works or something and you move it along, and then you end up creating a clinical trial around it with the actual inhibitor or whatever it is, and then you’re having an outcome on the medical side.

Dr. Matsui: Right. If something actually works, then you need to go back and try to figure out that you understand actually precisely how it works so you can make it better. So I think that it’s really a full circle of going back starting from the clinic and coming up with ideas for the lab and then working those things out in the lab and creating things for the clinic, and then you have to go and validate them by going back into the lab. It’s really this cycle and this engine that I think once you get that up and running — my experience at Hopkins was once you get that up and running, then it tends to go pretty quickly. I think that we’ve made pretty good progress here starting to get stuff off the ground. For sure, when I got here I thought, what am I going to do? because I don’t have any collaborators here. The lab has to rebuild itself. That was, yes, a very anxious time.

Jenny: Well, right. I mean, you’re trying to balance research plus your clinical practice. So you’re seeing patients, but you’re building a lab. And then you can’t do all research, so then you have to focus on what you think is the most effective. So how do you balance them? That’s tricky but perfect for a person like you.

Dr. Matsui: Yes, it is. Well, what I would say is that there are really great role models in medicine and in science who’ve been able to bridge all of these things and do them all well. There are many great people in myeloma who are able to do this. I think that for me, I would say a lot of it is trying to think or to be thoughtful about what things you put your energy and your time into and what things look interesting, but I think I need to be put aside.

So when I get ideas about needing to do X, Y or Z, I realize I cannot work 24 hours a day, but what are the most important things to get me to where I want to be in the next few years? So the clinical – we have to see patients. So what can we do to get that going? We want to plan for the future and have a really great, robust research program. So what are the steps we need to do right now? I think a lot of it is not saying yes to everything but trying to be thoughtful about the opportunity or to recognize that it might be an interesting thing, but I don’t see how it’s going to fit into my medium to long-term plan right now. And even though it sounds really cool, I think I have to just take a pass on it.

So a lot of it is just trying to not drive yourself crazy. For sure, there are these crazed workaholics in myeloma and who get an incredible amount done and they’re excellent clinicians, they’re excellent clinical researchers, they’re excellent lab researchers, they run big programs, they’re mentors, they do all of these things and they’re individuals that do all of those things really well, and there are a number of them in the field. I don’t think I’m necessarily one of those people. I just don’t have the energy that they have. So for me, it’s really more just saying, look, does this fit into where I think we should be in the next two to five to 10 years?

Jenny: It requires priorities, which I think is really important. Let’s talk for a minute about the importance of a myeloma specialist because as we’ve been meeting with patients, we’ve now met with hundreds, almost a thousand patients, one on one. The data shows and our experience shows that there’s a big dramatic difference in the care that people are getting if they see specialist versus if they don’t. So Texas is a very big place, and there are a couple centers that I know there that have some myeloma specialists. But just the need to see a myeloma specialist I think is really critical for patient outcomes. So from your perspective, how do you look at that?

Dr. Matsui: I totally agree. Austin is a little bit of a weird place because it’s grown so quickly. It is a bigger city than Baltimore, for sure. In Baltimore, there were probably about a dozen really good myeloma docs who specialize in myeloma. Here, there’s no one like that. I think that really you talk to people, like if I talk to people who are from Austin who’ve been here for 50 years, they all talk about it was a very sleepy, small college town where everyone knew one another, and now it’s a huge metropolis.

So I think that it’s really the pace of growth has outstripped how the medical system grows with it. So here there’s not necessarily an academic program here in Austin for any cancer care. A lot of it is through the US oncology system, which is a great system. They provide great care, and the doctors are very good, but it’s not something that’s focused on individuals. The majority of them are not focused on an individual disease.

So for me coming here, I think a big part of it was to say, look, I think that a great city like Austin that’s growing and vibrant, it’s weird that Austinites takes so much pride in the city, but if you get sick or if you get a cancer diagnosis, there’s a huge number of patients, it’s about 30% of patients, who’ll get their care in Houston, which is about two-and-a-half-hour drive. If you imagine you were getting RVD or something and you had to go get your Velcade once a week and it was a two-and-a-half-hour drive there and a two-and-a-half-hour back, that is directly impacting your life.

So I think that one of the big draws coming to Austin is that I thought that I had some area of expertise that could be useful to the city to provide some care. So for me, I think being a myeloma specialist here has been great. People have been really warm and welcoming, like the other oncologists who have been here or who are here. I think that one thing that I wanted to ensure from the very start was that I was not coming into town expecting to take care of every single myeloma patient in Austin. I just physically could not do that, but I think that providing some level of expertise and some level of academic thoughtfulness about how to take care of patients with this disease was something that I could do.

Just as you’re saying with the platforms the Myeloma Crowd has, how much variance is there in how myeloma patients are cared for on an individual basis? How much variance is there to that? In Austin, it’s huge. People take care of myeloma in a bunch of different ways. A lot of what I’ve been doing is seeing patients. I think that if someone is doing a reasonable job, a good job, and this happens the majority of time with the patient with myeloma, I would say to them, look, I think that everything is going well. And what I would say is that I don’t need to see you and give you maintenance Revlimid every month. I think that what I can do is see you every probably four to six months. If something happens in the meantime, then for sure, come back right away. But I think that I can provide expertise at one level but not necessarily directly be the primary care provider for that patient.

So patients who are in practices, just about every physician wants to take care of their own patients. I think that if they continue to do that, I can provide some help if help is needed. I think that over time, what we can do is create a more uniform way that we take care of patients in Austin, that it’s not like one practices x or one practices y. If there are differences, then we should talk about those differences and figure out why are there those differences and what does the data tell us and how should we approach this?

The goal is to not have a giant myeloma center that has thousands of myeloma patients. The goal is to make every myeloma patient treated the best that they can in the city of Austin. I can’t do that by taking care of every single patient. I just physically can’t do that, but I can do that more by seeing patients, and then we talk about what is out there, what trials are there. That is the way, I think, you can provide expertise.

I think it’s really important to have at least a visit with an expert. It’s not that people don’t know what they’re doing who are non-experts. It’s just that myeloma, you got to imagine 10 drugs in 10 years, it’s hard to keep up with what’s going on.

Jenny: Yes, that’s complicated.

Dr. Matsui: If you are treating breast cancer, lung cancer, colon cancer, sarcomas, and then you’re treating myeloma, I can barely keep up with the myeloma literature and if I had to do that for 10, 20 different diseases, there’d be no way I could do that. So I think that that’s what I try to provide as kind of a contemporary look at how we treat myeloma these days. This is the approach that we might take, and these are the options rather than saying, well, 10 years ago, we would have done something different. But maybe giving you thalidomide right now is probably not the best thing. There are other things that you could use.

I’m trying to improve the consistency of care in Austin. I hope to be a friendly face that people say, I have this patient and I’m not really sure what to do with this patient. Can I run it by you? I would love to be that person. But it’s not necessary that I have to take care of every single patient around. There are good docs everywhere. So I think that they should definitely take good care of their patients.

Jenny: Right. That’s a very effective strategy. I think that happens a lot in myeloma. You consult with a myeloma specialist when you’re diagnosed, so you get started in the right direction and then when you relapse, because you’re going to have to make another treatment change or some key decisions, so those key decision time points, I think, are the most important times to consult with a specialist.

Dr. Matsui: Exactly. So I think that’s really one of the reasons why in our clinic, I’m as important as the nutritionist, I’m as important as the social worker, I’m as important as the psychiatrist because all of those things need to be taken care of. But if someone’s on maintenance, I don’t know how many times you want to talk about Revlimid maintenance when you’re on maintenance. And there may be other things that we can help you with besides filling your Revlimid prescription.

So I think that as things become more chronic, there are other issues that come up and we want to make sure we take care of those issues. For some patients, for sure, their myeloma is the least of their problems, but we want to take care of the entire person.

Jenny: That’s amazing. Well, let’s transition for a minute to kind of more practical application of this new approach, this holistic care approach, but also innovation. Austin as a city is a very innovative city with a lot of entrepreneurship and innovation. So I’m sure you’re catching the vibe there as well. But there’s a ton of innovation coming out in myeloma – the immunotherapies and the newer therapies like selinexor and isatuximab and personalized therapies and using minimal residual disease testing.

So as you’re looking at creating this new practice, which ones do you pick? Which ones are the most interesting to you? Because you’ll have to create clinical trials and things like that that open at your center, so how do you prioritize those things? Maybe we just pick one that you want to talk about the most, and we just work our way through some of those.

Dr. Matsui: Right. On a very broad level, one of the major roles that a myeloma center plays is providing therapies that are not standardly available or doing clinical trials that are helping move the field forward. I think that to do clinical trials, you need patients. We’ve been approached about a number of trials. We need to wait and see what kind of patients we have. I don’t want to open a trial where there are no patients that are able to go on it.

So I think that, in addition to advancing the field, what you’re doing is you’re providing a service to myeloma patients because clinical trials should be a super important part of every myeloma patient’s treatment, like at least thinking about a clinical trial or hearing about trial, because that’s how you start to think about what are the standards and how are they going to change? What’s the right approach for me now? And how might that be different? How was it different than before, and how might it be different moving forward?

So for me a lot of it right now is just to see what kind of patients we have. Once we get a census of patients who are either relapsed or newly diagnosed or in post-transplant phase, then we can now start thinking about our patient population, maybe what we can do is we can devise or find a clinical trial that’s going to serve that population of patients. We know those patients are there, so we’ll be able to pull it off.

Who are our patients? Where are they in their treatment? What things do they need? Do we need a lot of relapsed/refractory trials? I think that that’s always a place where academic centers have been very active. Thinking about novel approaches, novel drugs, especially when people have unfortunately gone through most of the standard therapies, I think that’s an important role for an academic myeloma center.

I’m hopeful that we get some trials up within the next six months. But like I said, it doesn’t make sense for us to have a smoldering myeloma trial when I’ve only seen one smoldering myeloma patient.

Jenny: Right, that makes sense.

Dr. Matsui: I think that that’s one way to do it. I think of that, as far as what are the exciting clinical strategies, there are a ton. Myeloma is one of those things where you say to yourself, we have all of this and I don’t know what we can do any better. And then all of a sudden, there’s a whole wave of new things. Like with most other disease specialists, I think, how the immune system works is a very — it may be a way of actually controlling the disease in a very meaningful way. We’ve talked before about allo transplantation, and really allo transplantation is the first immunotherapy that was really clinically useful. That actually provides the proof that the immune system can control myeloma.

So now the question is, can we do that in safer ways or ways that are more effective than doing allo transplants? That, I think, is the next phase. I think that the immune system is still a little bit uncontrollable. I think that the questions of how do you do it? How do you do it safely? all of that, especially in lymphomas and leukemias, patients can get very sick from CAR T-cell therapy. It doesn’t seem like it’s as big an issue of myeloma, but it can still be very much an issue. I think that that’s important. I think that once you start exploring an approach like immunotherapy, then it becomes important to try to figure out, well, if it doesn’t work for everybody, then why is that the case? And then you can improve upon it and make the strategies better.

So I think immunotherapy is important. I am not necessarily a tumor immunologist, but I think that that’s got to be one thing that you think about. It may not be the forefront of what you do, but I think that that’s something that holds a lot of promise. I think that immune-based approaches that are not readily available standardly, those would be a pretty attractive thing to start working on. But like I said, what is the sweet spot in terms of who are the patients? What are the needs of the community? What can we feasibly and safely do here? In the end, are we contributing? Are we contributing to the field of myeloma? Are we contributing to the health of the city? And then most importantly, are we contributing to the health of our individual patients?

So I think if you could tick off all of those boxes, then I think you’re in the right place. But it’s a lot of work, a lot to get to that. But I think we’ll get there sooner rather than later.

Jenny: Well, let’s talk a little bit about your stem cell research too because we talked about that on a prior show. Maybe you want to explain that to listeners, what that research means in is. But now the CAR T development is a little further along, and I see them starting to do these dual CAR T studies like targeting BCMA and CD19 together and there are some other targets that are happening. There’s also other research that are targeting the stem cells. What’s the status of that in terms of myeloma, in terms of preventing relapse or killing it all when you’re going after it?

Dr. Matsui: When we talked before, this is a hugely controversial area. I think that if the research that we do has been criticized, this is the critical component of it. I think that if you say, well, why is that? Is it not really a concept across oncology, or is it something specific to myeloma? So if you talk to people in the fields of AML, they’ll say we’ve got to get rid of the leukemic stem cell if we’re ever going to cure patients. So there it’s very deeply embedded in the way people think about it. In terms of myeloma, I think that people intrinsically realize that most patients relapse, and then there’s some reason why they’re relapsing. It’s probably that not every single myeloma cell has the ability to regrow and to reproduce the tumor. That’s what causing relapse. It’s got to be some specialized population of cells.

So the controversy in myeloma is really, what does that cell look like? So if you think at a very simple level at a cell, there are two things about it that I think are very evident. One is what does it look like? Does it look like a plasma cell? Does it look like a B cell? What does it resemble? And then the second thing is, what does it do? So in the field, the controversy is, what does it look like? That is the main controversy. What I think is that it looks different in every single person. It looks different depending on if you’re newly diagnosed versus if you’re multiply relapsed. It looks different if you have a 17p than if you have a 4;14. So all these factors go into how it looks.

So I think part of the frustration in the field is that, well, it looks like it’s phenotype, it’s not the same. It’s not stable. So one way to deal with that is that in each patient, you catalog what every cell looks like and figure out what each one can do. Or the other thing you can do is you can say, look, I don’t care what it looks like. I care what it does. I think that for us, like the controversy in the field, I totally get this, is what does it look like? And that’s important for approaches like using CD19, or anti-BCMA because you need to target the proteins that are characterizing it. That’s what it looks like. But you’re not targeting the function of CD19. You’re not targeting the function of BCMA. You’re using those proteins as a way of getting the immune system, the CAR T to the cell.

So another way to think about it is what is the unique function of these cells? Well, one is that they need to last, they need to hang around after you give someone chemo, including a transplant, because if you got rid of them, then you would never relapse. So they have this ability to survive the chemo and persist. The other is they have this ability to start growing again. They can do that for long periods of time. They can remain dormant for a long period time and come up. So that property is pretty special. If you think about other tissues we have in our body like the bone marrow, it is only a few cells that are able to do that.

So in myeloma, one of the things we’ve done is to try and — I think it’s great to do these dual targeting things if you’re looking at what the cell looks like. I’m more interested in what are the processes that make the cell do what it’s going to do? What is its function? The function of the cell is what causes all the problems. It’s not what the cell looks like. So what we’ve been doing is really just focusing more on what are the pathways, or what are the things about the cell that allow it to persist over time? What triggers it to start growing again? What allows it to survive chemotherapy?

I tend to think about things that way. Like I said, I think that the function is what causes health problems. I don’t think it’s what the cell looks like. Plus, it’s hard to do things based upon what the cell looks like if it looks different in every single person. So for me, it’s like dysfunctional argument. That is, I think, somewhat irritating to people in the field because you want to know what it looks like. I tell people, look, I don’t know. I think it depends. It depends on the stage of disease, genetic mutations, what you’ve been treated with, all of these other things. I can’t tell you. What I can tell you is what it probably does. So let’s try to figure that out.

So that’s been my approach. That, I think, has been irritating to people because we originally found that things with CD19 we thought were important. I still think that that’s true in some patients but not all patients. But like I said, I think that you got to figure out what it does, and that’s how you can move the field forward at this point in time. Arguing about what it looks like, I think, is a pointless argument.

Jenny: It’s going to take forever.

Dr. Matsui: Exactly.

Jenny: It will take forever because then you have to catalog everything – I mean, a patient with three different genetic mutations now has to find the matching three different inhibitors. It’s like personalized medicine on steroids. Now you’re on five medications that might potentially hit part of that clone or whatever. I don’t know.

Dr. Matsui: Right. So I think it’s taking a step back and just saying, look, what are we concerned about within the concept? What we’re concerned about is people relapsing. So let’s deal with that. Let’s not perseverate over what is the markers on it? Look, let’s think clearly here about what our goal is. That’s how I think we should move it forward.

Jenny: Well, it’s very practical approach and probably faster. Well, when you think about immunotherapy, sometimes that’s what’s happening. You’ll apply these immunotherapies, and it doesn’t matter what genetic mutations are on the cells. It might even be just the status of someone’s immune system, or it could be something else.

So can I ask you just a strategy question? because I’ve been talking to a lot of different patients about what they’re taking for treatment options, and sometimes I’ll chat with them before they talk to their doctor about different strategies and even for myself personally. You think about it, these immunotherapies are coming past the phase one stage, whether it’s CAR T or whether it’s the BITEs or the antibody drug conjugates, some things like that. It seems like overall it’s easier to get these therapies and they’re more effective if you get them earlier. If you have this huge arsenal of drugs that you can go back to, you have Pomalyst and carfilzomib and maybe you go back to cytoxan or whatever. Wouldn’t it be better to try these immunotherapies in a clinical trial earlier rather than exhaust everything that you currently have and then go, oh, maybe I’ll try an immunotherapy now that I’ve been on 10 lines of therapy? To me, this myeloma thing is like a chess game.

Dr. Matsui: Right, I totally agree with you. I think that the most effective things you got to use earlier, like the earlier use the most effective things, I think the most bang for your buck you’re going to get out of them. I think that if they’re things that are potentially curative, they’re going to be potentially curative in more people the earlier you do them than after you’ve been through multiple therapies.

I think that that move is happening. In large cell lymphoma, they’re doing trials now. Typically, if you relapse with lymphoma, you go and you do a transplant. What they’re doing is there’s a big trial randomizing a transplant versus CAR T cell therapy. So it’s really like second line therapy there. I think that that’ll be interesting. In myeloma, I’ve been telling people that it may be that instead of doing a transplant, you get RVD and then do a transplant, maybe what we should do is to RVD and do CAR T cell therapy with the right CAR T cells. So that may be the best bang for your buck. It’s going to work better the less cancer you have. So that makes sense. If you give someone induction therapy and then give them something, that’s going to work better.

So I think that that move will happen. Like everything, it takes some time and it’s got to be a very systematic way of getting it there. But I have very little doubts that immunotherapy is going to be something that people get very, very early on in their treatment. That will, I think, have a big, big impact on the outcome of myeloma patients.

Jenny: It’s so difficult to make these decisions. I always recommend that patients just go discuss it with their doctor.

Dr. Matsui: For sure.

Jenny: But after evaluating these different options, you’re just thinking, well, you could go through the next two or three lines of therapy when you start relapsing and failing certain things that even core drugs like daratumumab or Revlimid or Velcade ixazomib or whatever it is and you just can see that pattern maybe potentially happening, I think, well, maybe it’s worth it to just go, if it’s out of a phase 1, you’re testing safety and dosing. But maybe it’s in a phase 2 and why not? I don’t know. Is there any reason why not?

Dr. Matsui: Well, I think that part of that is that it is really, like one thing that I will say is that there’s a lot of thoughts about and there’s thoughts here about using artificial intelligence to help make medical decisions. I am a person that says, well, that can be helpful, but it’s never going to be definitive. Part of it is that people are different. People look at things different ways. When people ask, well, what is the biggest job you have, what do you do the most for patients? I say, look, it’s really just like talking to people and saying, this is where you are. This is how you got here. These are the options for you. These are the pluses and minuses of the options. What makes sense to you? If I talk to someone for 15 minutes, half an hour about their myeloma, what they’ve been on, how they’ve done with that, I can pretty much guess what would be the best approach for them. There’s almost never a 100% or a decision that has only one solution. So really, it’s trying to match up.

I think personalized medicine is really what makes sense to you, to some extent, at this phase. Like I said, my job with patients is to explain things and say, this is what is going on. This is what we have available. These are the options. For you, I think that these might be things that I would think about. I think that that’s the approach I try to take with people. People are really smart these days and they have a lot of information coming in, but I think that they don’t know what option is best for them, so you have to walk them through that decision.

Jenny: Pros and cons.

Dr. Matsui: Yes. I think you cannot get a computer to do that at this stage.

Jenny: Well, going back to what you were talking about earlier when you’re thinking about not worrying about what it looks like, but how it’s functioning, why we’re relapsing, what research or initiatives do you think are going to be the most effective at addressing that function?

Dr. Matsui: I think it’s really coming up with really good ways of measuring that function. So if you have tests or things in the lab, assays in the lab that really point to those things, now you can start testing different things and seeing if you can inhibit that function. So right now, I think the biggest thing is trying to come up with ways of accurately measuring those functional properties. It’s not just having does the cell grow or not? It’s like, does it grow over time? That’s a different way of thinking of it. So it’s really like, right now, I think it’s developing good assays so you can test a bunch of things to do it. That is trying to test a function.

So that’s where the field should be. I think we’ll get there. And then there are ideas about what things we should test and what things we should look at, and then I think we can take it from there.

Jenny: Right? Well, I’ve monopolized all the time. We may have time for just one question. So if you have a question for Dr. Matsui, you can call 347-637-2631 and press 1 on your keypad. I might just take one caller question. Go ahead with your question.

Caller: Hi, Dr. Matsui. How are you doing?

Dr. Matsui: Good. How are you?

Caller: I’m great. Just one question for you. I started seeing some research I think came out of New York about the microbiome, and the patients with healthy gut bacteria might respond differently to treatments. Do you have an opinion on that at all?

Dr. Matsui: I think that it’s probably true. The adage of you are what you eat is kind of like that, to some extent. The microbiome is more things than just the gut, but they have to affect the human body. So I think that the challenge right now is figuring out, of all the different creatures and critters that you’re symbiotically living with, what things are good, what things are bad, and how are they interacting with things? And so it’s back to the stage like in the beginning, when we were thinking about sequencing, you get millions of pieces of data and then what how do you make that into something? I think that with the microbiome, we’re kind of at that stage of being able to collect the data. And now we can generate ideas about what should we try to change, and how should we test that?

So I think we’re going to get there. I think it is important, but I think that right now it’s just too much information to be able to synthesize and come up with strategies where you know what you’re doing. But I think that that will be the case in the future. I think that the microbiome is going to be pretty important.

Caller: Awesome. Actually, I also do have a follow-up question. You were talking earlier in the interview about the challenges of creating a new specialist center. I was wondering, how do you use technology and leverage it effectively to maximize your time as a specialist across multiple patients and across multiple doctors?

Dr. Matsui: I think really that is evolving because medicine is a people-based business and having technology in that is important. We do a lot of patient surveys to make sure that we’re addressing the right things with patients and then that we have the right approaches so we can alter them if we need to, to better serve our population, and that is really technology driven. So the way we collect data on patients is all based on technology. It would be impossible to do it by hand. We’re trying to do things like do more telemedicine-based things where you don’t have to go to a doctor. You can interface with your physician and the medical team through apps and stuff like that.

So we are trying to do those things which I think it will make it easier. But in the end, a lot of being a physician is talking to a person, and that part is you have to figure out what parts of that you need to keep and what parts you can try to streamline through technology. But for sure, I think we’re in better shape now than we were 5, 10 years ago.

Caller: Thank you.

Jenny: Great. Thanks for your questions, and thanks for the great answers. Okay, one more question. What’s your question?

Caller: Hi, Dr. Mitsui. This is Greg with the Myeloma Crowd. I attended a clinical meeting a couple of weeks ago. Dr. Anderson made a comment about phase 3 trials, that they’re basically too large and take too long to complete. And then Dr. Lonial after that mentioned that phase 3 trials are not really relevant in his decision-making process with patients. Do you have any thoughts on that? Do you think the current clinical trial structure is relevant to a field like myeloma where we’re constantly stratifying patients out by their biological characteristics?

Dr. Matsui: I think you can design trials in a way that take advantage of those individualized things about people. I think that one thing about Phase 3 trials is important. I think that this came up recently in the testing of a drug called venetoclax. I think that what most people would not argue with want people to live longer. That’s really an overall survival endpoint. And in the venetoclax study that was a combination study, if you add venetoclax to other chemotherapy, more people get responses, your progression-free survival or the time it takes before you relapse essentially is longer, but the patients lived a shorter amount of time. So that doesn’t all makes sense.

So if you do shorter trials and you do them where there’s no control arm, it’s very difficult to know, in the end, are you making an impact on overall survival? And the reason why I think that overall survival is important, for me overall survival is the most important thing. I think that that’s why I study myeloma stem cells because I think that stem cells are responsible for how long you live overall. So I think that phase 3 trials do have some role in terms of establishing definitively, to some extent, what should be the standard, what is going to make a population of patients live the longest? That should be the standard. And if you do everything off of these earlier endpoints like progression-free survival, at some point, you’re going to make a mistake. I think that you don’t want to establish that as the standard and have people live shorter.

I think that there is a role for phase 3 trials. I think that phase 3 trials, it’s not that they’re difficult to do in myeloma. There are a lot of great phase 3 trials done, but I think that they need to be done thoughtfully. I think, in the future, they need to take into consideration things like specific molecular abnormalities that people might have and MRD and all of these other things. But for sure, you want to have people live longer and to do that, you need to study overall survival. Really, the only meaningful way to do that is in randomized trials which tend to be phase 3 trials. So I think they do play a role.

Caller: Thank you.

Jenny: Great. Okay, we have one more question. Do you have time?

Dr. Matsui: Yes.

Jenny: Caller go ahead with your question.

Caller: Hello, Dr. Matsui. Can you hear me?

Dr. Matsui: Yep.

Caller: Okay. I was at that same conference as Greg that he just mentioned which was really wonderful. There was a lot of conversation about looking at the bone marrow microenvironment and the immune system trying to identify more specifically, and this is my language, with deficit different people have that’s allowing relapse and/or drug resistance so that immunotherapies could be better matched up to them. Do you think that’s like a compatible concept with also looking for stem cells? It seems to be a different avenue. Could you comment on those two things?

Dr. Matsui: Yes. I think that the environment is super important and probably many facets of the disease. We and other people have shown that cancer stem cells are deeply affected by their environment. It makes total sense because normal stem cells are completely reliant on their environment to tell them what to do. In the same way, the environment affects things like how cells respond to different drugs, how the immune system is working well or not.

So I think that the environment is something that hopefully is something you can modify and modulate to make things better. Whether or not we can understand it in a meaningful way is a challenge. I think that we don’t have great lab models to try to figure out what’s going on that are really super accurate in terms of telling us what’s happening in patients. But I think that those will get better over time. I think that understanding how everything integrates together, how do stem cells react to the microenvironment, and what effect does it have on the immune system and then what effect does it have on drug sensitivity or resistance, all of those things are connected up in some way. And right now what we do is we study each one in isolation. But at some point, I think you got to merge the concepts together. We’re starting to try to do a little bit of that.

Caller: Okay. And part two is a paper just was published by a group of about 10 doctors, and some of them are at the University of Iowa. They were talking about the myeloma cells that are CD24+. They are like tumor-initiating cells which I think are like stem cells. They tried the monoclonal antibody against CD24, and it was effective. Can you comment on that? Do you think that’s a pathway to keep going down?

Dr. Matsui: I think it is. I think that, on one hand, for sure, people have been studying CD24. There’s a big paper out from a group in California where not in myeloma but in other diseases, they showed that targeting CD24 was really effective at modulating how tumor cells interact with the environment, especially the immune environment. So I think that people are on to already targeting CD24 outside of this finding in myeloma. So I think you could bring the CD24 concept in pretty easily.

I think that the issue I have with this CD24 paper is that — it was well done. The group is very good in Iowa. The problem is that it’s focusing on what the cell looks like. So this is the issue of does every cell that has CD24 tumor-initiating cell or a stem cell? Are there cells in there in a person or amongst different patients where the tumor-initiating cells don’t express CD24? So I think that this whole thing about what does the cell look like is a concept that we should get over. We should get over what they look like. We should focus on what they do. I think that that might be a way to think about it.

Like I said, I liked the paper. I thought it was well done. I thought conceptually it was novel. But this fixation on what do the things look like is basically what’s dragging down the field, I think.

Caller: Okay. Well, I think I can probably say that if you were to develop a clinical trial trying to define how these stem cells function, a lot of people would come to Austin for your trial.

Dr. Matsui: That would be great. We will love to have that.

Caller: Thank you.

Jenny: Okay, well, thank you so much for your question. Thanks. Dr. Matsui, thank you so much for going over time. I’m so sorry, we went over so long with you.

Dr. Matsui: No problem.

Jenny: But I really, really appreciate you joining us. I think what you’re doing in Austin is fantastic. We hope that you have a successful clinic and research project and lab. Anything we can do to help support you, we’d be happy to do that.

Dr. Matsui: Thank you so much. I appreciate being able to come on and talk about what we’re doing.

Jenny: It’s very exciting work. So we’re just so thankful there are people out there like you.

Well, thank you so much for listening to Myeloma Crowd Radio. We invite you to tune in next time to learn more about the latest in myeloma research and what it means for you.

About Author

Jenny A

Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical trials. Founder of Myeloma Crowd, Myeloma Crowd Radio and the CrowdCare Foundation.

One Comment

  1. Karen Waters September 13, 2019 at 4:04 pm

    You folk didn’t mention smoldering MM and if the doc is going to work on treating it before it becomes full blown. I feel like a ticking time bomb. It’s very depressing! Karen

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