Speaker 1:
It's great to see everybody here today. We pretty much packed the room yesterday and somehow we've put even more people in today. We're just around the 200 mark, which is really remarkable for us. So thank you everybody for joining us today. A couple things, as Diane shared with us, the reach that the IMF has is quite dramatic and we're very thankful for that in every respect. But one of the areas that we thought we'd take just a few minutes to talk about this morning is going to be clinical trials.
Robin yesterday asked people in the room, how many people here have participated in clinical trial? And I got to ask the question again just one time. How many of you have in some capacity participated in a clinical trial? Okay, so there's actually quite a few of you, but still a lot of opportunity. And so when we say the word clinical trial, it tends to invoke an interesting response. And it can be highly varied based on your personal experience, your race, your ethnicity, your understanding, the media.
So here, Dr. Joe is going to try and simplify things for us and really get to the heart of what are clinical trials, why are they important and why they may or may not be particularly valuable to you. So really what I want to do is give you a little sense of how do they fit in the bigger picture of development. You heard me talk yesterday about all these incredible drugs that we've developed in myeloma. What role do clinical trials play? And as I often say yesterday was really the appetizer. The main dish comes today, right? We have a lot of outstanding speakers today, I'll introduce them in turn. You'll meet Dr. Kumar, Dr. Lee, Dr. Janet Kinran, Dr. Vessio. Several are going to join me on the stage over the course of the day.
We'll talk about what are the phases of a clinical trial, what's a phase one trial versus a phase two trial versus a phase three trial. And then we'll have a little bit of a discussion about the risks and benefits of trials, and then we'll have something a little special at the end. So if you're going to nap because you're a little sleepy from the scrambled eggs this morning for the next 12 minutes, which is really only how long, or 15 minutes that I want to speak this morning, here's the take-home message, we would not be where we are today in myeloma if it were not for clinical trials.
Some of you heard me say yesterday when I started a myeloma a little over about 25 years ago, the average survival of our patient was between one and two years. Now, as you're going to hear from Dr. Lee, and as we're going to discuss shortly with Dr. Kumar, we now expect that the average survival of myeloma is well over a decade. You can clap for that. And I noted yesterday I remember the four hot topics we talked about. The topic number four was that for really the first time, and I think Dr. Kumar can attest to this, because he was the one presenting this at our International Myeloma Working Group, we started to use the word cure because we're not typically comfortable using the word cure. I'm not saying we've cured myeloma, but there is perhaps a smaller fraction that is growing of patients that we're typically going to cure.
So we wouldn't be here where we are today if it weren't for clinical trials. And no one is expecting you to be a guinea pig to go through something that is not going to be of benefit to you. If there's one message I want to leave with you about clinical trials, clinical trials are not about signing an organ donor card that benefits someone else, but frankly doesn't benefit you. I'm not saying it's wrong to sign your organ donor card, please don't mistake me. But sometimes when people hear about clinical trials, they're like, "Oh, it's such an honorable thing to do to help others in the myeloma community." I want you to be selfish, right? I want you to think about you, "Is this clinical trial going to help me?" And that is the point of them. The point, as I'll share with you in a few moments is to give you access to something that you otherwise would not have access for.
So yes, there is a benefit to the greater myeloma community and we understand it and understand more about drugs and the disease, but you're not going into a clinical trial, if you will, to just make a sacrifice for the sake of the myeloma community. It's really for you. Research is under very tight supervision and standards. We have a sordid history that I'll come to very briefly later that has unfortunately led to a lot of mistrust in the system and some terrible things that have happened. But in reaction to that, we now have a very tight system of supervision.
And then lastly is, as I intimated yesterday, more than intimated, as I clearly stated yesterday, when you have an open, honest, clear relationship with your healthcare team, it improves your outcomes. We've demonstrated that in oncology more than any other field of medicine, as I noted. One of the reasons why those outcomes are better, we say outcomes, we typically mean people staying in remission longer and actually living longer. And that's been proven in oncology. One of the reasons for that is when there's that open, honest communication, you're more willing to share that symptom that you're experiencing. You're more willing and you trust your team, you're more willing to follow their advice or to take the medication. And part of that includes being willing to be on a clinical trial.
In fact, when people report that they have a better relationship with their healthcare team, they're much more likely to participate in a clinical trial. So now you can nap for the rest of my talk. So a few myths to kick it off, because sometimes people say, "Well, if I participate in clinical trial, I might get a placebo, not active treatment." That's not how we do it in myeloma. The only time we ever use a placebo in myeloma is if you are getting a placebo plus what the standard of care is.
So it's not like saying... I can't ethically say, "Oh, someone's got very advanced multiple myeloma. Let's compare drug A to giving them nada." Right? We're not going to give you nada when your disease is active. You're not going to just be taking a placebo in that way. Everyone gets as much of the standard of care as possible when we use a placebo. If I participate in a clinical trial, I can't change my mind. You're locked in as you've heard me say before, "You'll take it and you'll like it." No, that's not how we do it with clinical trials.
One, you have to be able to make informed consent as I'll discuss at the end of this talk. But also you have the opportunity to change your mind, as with any other treatment. So people sort of think, "Well, if I do the clinical trial, I'm kind of locked in." We don't encourage people to drop a clinical trial once they're on it. We want you to go in eyes wide open, but sometimes there are things and situations where people do have to change their mind and that can happen.
The next myth, clinical trials are dangerous because they have new medicines and practices. Let's talk about this for a second. Every drug, as we commented yesterday, comes with a risk, right? Outside of mother's milk, everything pretty much is a risk that we would take in life. And again, I'm not making light of it, but we balance risk and benefit in everything we do. For those of you who are LA based here, you drove here today, right? Mostly or perhaps took an Uber or it likely involved a vehicle, right? Getting into that vehicle was a risk, but you recognize the risk compared to the balance of having to walk here, which could be an LA even dramatically riskier. You take that risk benefit analysis in your mind and you say, "Is it worth doing?"
By the time a drug has reached you for a clinical trial, as I'll show you in a few moments, it's gone through rigorous assessment. Not to say we fully understand it, we still have to be careful and I'll explain what a phase one clinical trial is in a moment. But yes, everything does come at a risk and we have to be very careful with that. And the FDA is very clear. I commented yesterday about the FDA's assessment of one of the drugs that is undergoing evaluation, that they were particularly careful about safety, which is what the FDA does, right? That's meant to protect the public. We get that. But we don't want to make it sound like clinical trials mean, "I'm just taking this Hail Mary pass. I'm trying something that is never been heard of before and we're just trying to throw this together to see if it may work, and I'll throw it against the wall, see if it sticks."
By the time the molecule is brought to a clinical trial, there's about 50 other molecules that have failed to get to that one, that the likelihood that this is going to have activity is considerably higher. And then lastly, at least of some of the myths, there's so many I could cover, clinical trials are expensive and not covered by insurance. Now obviously we heard about the complexity of insurance yesterday from our friends at Triage Cancer, but more often than not, insurance programs and plans will allow patients to participate in clinical trials. Often if there isn't full allowance through the insurance company, there can be other means to make up the difference because typically insurance company has to at least provide the standard of care.
And so this is something that is worth discussing. Now, I've been like Dr. Kumar, Dr. Lee. We could talk about patients we've treated for decades now on clinical trials, I can literally count on one hand how many times we've really been in a challenging situation where someone's insurance company was questioning the clinical trial. So usually that's not the case. Sometimes there can even be certain benefits that can facilitate your care in clinical trials, as some trials will have budgets for transportation and for other things that may involve extra visits that you wouldn't routinely have in your regular care. Okay? Oops, sorry, I skipped one there.
So why? So why are we even having this conversation? What's the point? Well, of course everybody has to be uniquely viewed. But really the key point here is that you have access to a newer therapy that's not yet approved, that you have that early access that the soft opening to the restaurant that's not going to open for several weeks later. You have that benefit of getting into it early. And in a lot of situations, our patients need that access because other options are not available to them because they've gone through other options or they want to be able to save those other options for later. And this new promising therapy.
For example, yesterday someone asked a question about one of the newer CAR T's that are being developed, ide-cel, I'm just picking it as one example, that there may be an opportunity to participate in a trial that includes a drug that may be as efficacious and possibly even safer than what the standard of care is now. So the idea is your own benefit. It's again not to just give benefit to the greater myeloma community. It is to benefit you. By doing so, you can delay the current standard of care. You have that opportunity to delay it for later. Of course, as I mentioned, there is potentially benefit to the myeloma community and financial benefit, but that of course has to be balanced with risks. Every drug comes with risk. There is a chance of toxicity.
Sometimes when drugs are newer, we don't fully understand all the realms of toxicity. As I'll show you, we do tests in the lab, we do tests in mice. We do everything we can to try and understand it, but sometimes when brought into humans, it can be different. So that has to be thought of. More often than not when you're participating in a clinical trial because a much smaller fraction of patients get treated in those early phase trials. Typically, by the time a clinical trial's been offered to you, it's gone through that very rigorous safety analysis. So more often than not, we know the side effects and we share them with you before we go in.
And of course there is a chance that it doesn't work. Not everything works. We know of course that has been, I commented yesterday that the vast majority of drugs approved in myeloma before CAR T and bispecifics were approved on the basis of showing that it works in 22 to 32% of patients. Now with bispecifics and CAR T, we're seeing response rates in the 60s, 70s, 80s, and ever over 90%. So how does it work? Well, number one, we got to figure out how we can attack myeloma. That's why research is so important. We're going to... Diane made some comments about all the different aspects of the work of the IMF, and Robin made comment yesterday of our scientific advisory board of which Dr. Kumar is on, and we're going to hear from him shortly.
One of the beautiful things I think that the IMF does is it helps, if you will, convene the world of myeloma. I often say it this way, why are so many world records broken at the Olympics? Including the gold medal that Diane's family now treasures as she shared with us. Why do people break so many records at the Olympics? Because the atmosphere is set for people to perform at their highest level. That's what we want to do as the IMF. We're not City of Hope, we're not Mayo Clinic, we're not UCSF, we're not UCSD, but we bring together those individuals to perform in a way to allow them to develop collaborations that they might not have individually in their own individual center.
And so I'm being a little bit of a commercial for the importance of research. And as you know, research to some degree is being attacked in the country in the bigger sphere. I'm not trying to say anything political or apolitical, that's not my purpose. My purpose is to say that we want to support basic research because research does not just involve do clinical trials. We can't do clinical trials if we don't understand the disease. You can't attack the disease if you don't know how the disease lives. So very often the first step is identifying in the lab, how do we attack this myeloma?
Remember I showed you that picture yesterday, for those who are here of a myeloma cell with all those things that stick out of it, some of them we don't even understand. Those different antigens, right? You're all experts now in antigens, all the license plates, BCMA, FcRH5, GPRC5D, all those different targets, we have to understand what those targets are if we're then going to be able to use them and leverage them to attack multiple myeloma. So then we say, "Okay, well we've found this target. We've developed a drug that we think could hook onto this target. Now let's test it in the lab." And we have cell lines in the lab, literally collections of myeloma cells that are outside of anybody's body. And one of the colleagues when I previously was at Mayo Clinic and as a colleague of Dr. Kumar's in Arizona, has one of the most sophisticated cell lines and mouse lines that there are in the world of myeloma.
I know, as I'll show you in a moment, it's a little bit disturbing actually how similar we are to mice. I know that's not the most uplifting sentiment in the world. But we do these tests to see if this drug may work. Is it really hooking onto to that target? Is it really working? And then we bring it into the realm of clinical trials. So even before we get to phase one, we're testing this, as I've said on cell lines, which we call in vitro or even a mouse model. We have a very sophisticated mouse model for this at Mayo Clinic, and then we come to the first of the clinical trials that are sometimes called the FIH or first-in-human clinical trials. This is an area of work in the clinic that I have. I work primarily of course for the IMF, but I do retain a small clinic and do clinical trials in Arizona. And here we have a phase one clinic where often we're testing molecules for the very first time in patients.
And so the concept of a phase one trial is, yes, we want to make sure this drug works, but before we make sure it works, we got to make sure it's safe. And so we typically start at very, very low doses. A lot of times we're allowed to increase the dose even in that particular patient if they don't respond to that very low dose. So if we think the dose is going to work at let's say one milligram, we might start a 0.1 just to be super safe to ensure that there isn't any unusual side effects as we build up and then the doses get higher. And the goal of the phase one trial is really to understand what is the dose that we can give here.
Sometimes it's called the MTD or the maximum tolerated dose. I don't want to get into too much detail here, but we want to basically find the right dose that is safe for that patient. And then we move into a phase two trial where we say, "Okay, how well does this drug work? Let's do it in a larger group of people." We use a smaller group of individuals to make sure, typically three patients per dose level. And then once we say, "Okay, you know what? We actually think that one milligram is a safe dose to give to patients. It looks like it's starting to work. Now let's taste..." Taste. Let's test... I'm still hungry, apparently, "Let's test the one milligram dose in a hundred patients and see how it works in that group." And that's what we determine. A lot of drugs carry on then and some drugs don't make it after this. It doesn't show the efficacy that we need.
And then finally, we hit sort of the granddaddy of them all the phase three trial. And the phase three trial says, "Okay, you think this drug is that good, let's compare it to the standard of care." And often it's comparing drugs like this. So if I've developed a drug X, I think this drug is particularly useful, but really right now we're typically in this scenario using drug A, then we'll say, "Let's do a clinical trial that compares drug A versus drug A plus X." So both arms are getting drug A. Both arms are getting the standard of care, but that second arm we call the intervention arm, is getting A plus X getting that see if that benefit is exceeded by having those two drugs together.
So a lot of the trials that you'll hear Dr. Lee talk about in frontline therapy and Dr. Janet Kinran talking about in relapse therapy, as we go over the course of the day, have compared two drugs to one drug or four drugs to three drugs, or sometimes just three drugs to three drugs. We may switch out a drug because we want to make sure that no matter what people are getting at least the standard of care and then potentially a further benefit beyond that.
Often patients are so-called randomized to one of those two. We don't just handpick and say, "Okay, you get to do this drug, you get to use this arm versus that arm." It's done randomly by a computer so that there's no human influence on it, so we can truly say, "Yes, that was a difference." And often it's blinded so the patient doesn't know. And often we as the medical team don't even know. I think of the taste testing between Coke and Pepsi or something. If they hand you, "This is your Pepsi, this is your Coke, which one do you like more?" Well, you're already going to be biased in your mind. But if I blind you to it and say, "Here's a drink and here's another drink, which one do you like more?" It gives more objectivity to the situation.
So to piece them all together, then we have these pre-clinical phase one, phase two, phase three trials, and then there is something called phase four trials. This is typically after a drug has been approved where we want to get more real-world evidence around it. Now that it's being used by many more and more people in the community, there are lessons and there are things that we can learn through that process. Then to wrap up here, before I talk about diversity in trials, to wrap up, let me just summarize that the possible benefits of a trial is that you will at least, minimum get the standard of care, but that you have this opportunity to be exposed to a new treatment, a new intervention. And for a lot of our patients, this has allowed them to live longer and live better.
I think of some of the patients we had the privilege of treating several years ago before CAR T and bispecifics were available, that got access to CAR T-cell therapy 5, 7, 8 years ago and are still with us today, who otherwise had very limited options. And that's really the goal of what we can do. At the same time, we balance that with the risks. You have to go in eyes wide open. It's not all rose-covered colored glasses here that everything is going to be cheery and happy. There are some challenges, there are some risks, but very often we would not be offering you a trial if it weren't for the fact that we think that those benefits outweigh the risks.
So why do so few people participate in clinical trials? Well, part of it is people aren't aware of it. There may not be access to trials where someone lives. And this has been a huge work of the medical and particularly the myeloma community, to find ways to have greater outreach into the community. And there's of course a history of fear and distrust, mistrust as I've already shared with us already. Sometimes there are, as mentioned can be some insurance issues. Some people might say, "Oh, well, if I go to a center that has clinical trials, am I cheating on my doctor?"
Let me talk about this for just a second here because this happens to me a lot because in my clinic I do a lot of what I prefer to call expert opinion. I prefer not to call it second opinion because second opinion makes it sound like the first one was wrong. But when we encourage people to see a myeloma specialist, if they can, because myeloma is complicated. Remember I showed you yesterday 2% of all cancers. So the average community oncologist takes care of breast cancer, colon cancer, lung cancer, prostate cancer, the big four accounts for about 80% of their practice, and then the other 40 cancers account for the rest of it. And so they want input and they want insight.
So typically when a patient says, "Can I go see Dr. Joe in Arizona and get an expert opinion." They thinking like, "Don't tell my doctor, right?" It's like they're having an affair. You're not. It's okay. You are allowed to go and do this. This is for your own benefit. In fact, I've been doing this for over 20 years. I can literally count on one hand, in less than a hand how many times that doctor of the patient was actually upset by it. More often than not, they're happy, they get more insight. Even my own patients to say, "Can I go see someone?" "Absolutely. Go see Dr. Kumar in Rochester. Go see Dr. Lee here in LA." We encourage that because it gives you that greater insight.
So don't feel that leaving your community oncologist and going to an academic center, for example, to do a clinical trial is cheating on your doctor. That's not the point. Then of course, there are places that just can't offer clinical trials. Part of the reason we've seen this reduced participation trials are in populations that have historically been underrepresented in myeloma. Later today, I'm going to give you a very short talk on health disparities in myeloma and what the IMF is doing to overcome that with our really, I believe, extraordinary program in the M-POWER Program.
But to cut to the chase with a couple of the numbers here, about 20% of myeloma patients in this country are of African descent, and yet historically, if we look at representation of African Americans clinical trials, it's generally below 5%, at best, between 5 to 8%. And why is that? Well, as I've mentioned, there's a lot of reasons behind it that can have a lot to do with the history of terrible things that we've done in clinical trials, lack of trust in the system, lack of access, lack of healthcare insurance, a whole host of reasons, even just within the healthcare system itself. But this is important because it's not just saying, "Oh, we want to match a number to a number."
I want to make sure when I sit down in front of a Black patient or a Latino American patient, I want to be able to say, "When we did the clinical trials to prove that this drug is safe and effective, I can say it's safe and effective in you as well, and not just a group of people that may not be represented." Because we know biologically there are differences. I commented yesterday, those of African descent have twice the risk of developing myeloma. If you're a Latino American, you're likely to be diagnosed with myeloma younger. So there are biological differences, and so it's incumbent on us to just say, "Oh, it doesn't work in just this group of people. It really works across the whole spectrum of myeloma patients." Which is one of the reasons why we created this program called the Diversity in Clinical Trials peer-to-peer program, where we brought together six individuals, five were patients, and one was a care partner from historically underrepresented communities in research and in clinical trials to come and share their story, to share what it was like to be on a clinical trial.
Because let me tell you, it's one thing to hear it from Dr. Joe, and thank you, by the way, for all of those of you who have come and said that you've been watching the videos that we do, I know Diane shared with us some of the numbers, and I'm sorry that you have to see my face as much as you do, my electronic stalkers that you are. But I love that you're watching these. But it's one thing to hear it from Dr. Joe. It's much different to hear it from a peer. That's one of the reasons why we have these amazing support groups because hearing it from someone who's been through it, I can tell you what it's like to go through a transplant because I've done thousands of them, but it's a lot different when you hear it from someone who says, "I was on the receiving end of the melphalan. I was the one barfing when that happened. I know, and let me tell you what it was really like."
And so these individuals have shared their story. We've captured them on video. We've had the opportunity to have them join us at different events. We, for example, we always do a Juneteenth event in New York City. And one of our patients came with me and sat on the stage in this large church in Brooklyn and was able to share her story of what it was like and how she talks about the fact first time she heard someone say clinical trials, she said, "I literally covered my ears," like, "I don't want to hear it. That's not for me." But that eventually she came to realize that it was something of tremendous potential for her and benefit for her.
So with that, I am going to, after this slide, I'm going to actually show you one of those videos from one of those patients. But I leave you with this checklist that I often have for patients, and we have this in different forms at the IMF, including as Robin shared with you with the QR code, you can download these slides. These are available to you, but the kinds of questions that you want to make sure you ask if you're discussing a potential clinical trial with your healthcare team, things like, "What are the side effects? What do I expect? How many trips am I going to have to do? Can I keep taking this medication? Can I keep taking that medication?" We are so meticulous with those things, with individuals going through trials that they're going to walk you through it. So with that, let's cue up the video and have a little listen.
That gets me every time. For those of you who know Thomas, I suspect some of you do. What he says on video is real. That's the way he lives his life, and he has really been a role model for many of us. So with that, I'm going to wrap up this session and remind us that later today we're going to have an opportunity for more extensive Q&A. We have, as I've mentioned, a whole series of wonderful doctors. I think I just saw Dr. Vessio make his way in, and others are going to be here today, and we'll have an opportunity to talk a little bit more about not only clinical trials, but all of multiple myeloma.
Before we move into the session with Dr. Kumar, I just want to remind us of what Robin shared with us yesterday that the IMF has gone into a partnership with SparkCures, which is an organization that's really built an incredibly sophisticated search engine for clinical trials. Where you can go in, you can go in as if you will, anonymous and not give any personal information and just start to look for trials, "I live in the San Fernando Valley and I'm looking for a clinical trial in myeloma." And it can tell you what are the trials in the area here, whether it's at UCLA or USC or City of Hope or Cedars. It'll give you what order the trials are.
You can go even to a deeper level and say, "Well, I have relapsed myeloma and I've had these two treatments before." And it can narrow the focus for you, and it'll give you that information to be able to search for trials that are potentially available to you. And if you haven't had a chance to do this, just go to our website, myeloma.org/sparkcures, you'll see it there, and you'll be able to do some of that searching. And as you heard from Diane this morning, we've had thousands and thousands of searches already done, even just in the last six months or so.
With that, I am now going to call up my good friend and colleague, Dr. Shaji Kumar.
