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    • Myeloma Crowd Radio Episodes
    • Oct 02, 2019

    Full Show: The World’s Largest Myeloma Screening Study (PROMISE) with Irene Ghobrial, MD, Dana Farber Cancer Institute

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Irene Ghobrial, MD
Dana Farber Cancer Institute 
Interview Date: September 4, 2019

Thanks to our episode sponsor

Summary

The PROMISE study is the world’s largest screening study for multiple myeloma and is led by top myeloma researchers Dr. Irene Ghobrial of the Dana Farber Cancer Institute and Dr. Ivan Borrello of Johns Hopkins. Dr. Ghobrial plans to invite 50,000 participants that include two key groups of people who are more likely to develop multiple myeloma. The first group is family members between the ages of 40-75 of myeloma, MGUS or smoldering myeloma patients. The second group is all African Americans, who are 3 times as likely to develop multiple myeloma. Learn how your friends and family can join this important study that will tell us why myeloma develops and how we may be able to receive earlier, better treatment that could prevent it from developing into active myeloma in the first place. 

Please share this important study with at least 5 friends and family members today! 

Join the Promise Study

Dr. Ghobrial 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, Karyopharm Therapeutics, for their support of this program.

Now, before we get started, we’d like to share a short update on the tool we created called HealthTree. We created HealthTree to help you as a myeloma patient better navigate your disease or your active myeloma or precursor conditions. You can track everything about your myeloma in a single place. You can see personally relevant treatment options if you have active myeloma. You can find clinical trials you’re eligible to join, especially if you have active myeloma but also if you have precursor conditions. Soon you’ll be able to find a twin, or other myeloma patients with similar features that you have and connect with them via chat.

Another thing you can do in HealthTree is you can contribute to myeloma research. One example might be that we’re starting a study to see if there’s a connection between psoriasis and multiple myeloma using HealthTree data and other questions. But another example is the show we’re going to be discussing today. When you log in to HealthTree, in your dashboard, you’ll see an option that says Accelerate Myeloma Research, because as patients, we can do a lot to help accelerate the field of research. We’ll talk a lot about that today. But if you want to join the PROMISE study that we’ll be talking about today or you want to invite your family members to join, you can mark yes and then Dana Farber researchers can contact you on that.

So this is really an ideal way for patients and family members to contribute to a cure for multiple myeloma. In this case, you’ll be helping to invite friends and family join the world’s largest myeloma screening study of over 50,000 people. This study is being led by a truly incredible myeloma researcher, Dr. Irene Ghobrial, from the Dana Farber Cancer Institute, who is an expert in precursor myeloma conditions. It’s her goal, as you’ll hear later, to eliminate the disease from progressing from these early conditions to active myeloma. Stand Up To Cancer has put $10 million behind this study. We are just so excited that she’s working on preventing this disease from happening in the first place.

So with that, I’d like to welcome Dr. Irene Ghobrial to the program.

Dr. Ghobrial: Thank you so much, Jenny. It’s really my honor to be on this call.

Jenny: Thank you so much for joining, and we look forward to hearing more about it. But before we get started, let me just give a brief introduction for you.

Dr. Ghobrial received her medical degree from Cairo University School of Medicine in Egypt, and she is attending physician in medical oncology at Dana Farber Cancer Institute and Professor of Medicine at the Harvard Medical School, so it’s very exciting. She’s Director of the Clinical Investigator Research Program at Dana Farber and Director of the Michele & Steven Kirsch Laboratory.

Dr. Ghobrial is a physician-scientist who specializes in the field of multiple myeloma and Waldenstrom’s and specifically in the precursor conditions of monoclonal gammopathy of undetermined significance or MGUS and smoldering disease. So she focuses on the role of how these precursor conditions progress to active myeloma. She initiated the Center for Prevention of Progression of Blood Cancers where patients with these precursor conditions will be monitored for different evolution to see why they progress and how. So that’s a tissue bank study where patients can join but don’t need to travel. Now, she’s the lead primary investigator for this new trial called the PROMISE study.

You will be able to do a better job at describing this study. We’ll ask a lot of questions around it. So let’s get started first by asking just some general questions about just the status. What are we learning, in general, in therapy and MGUS and smoldering myeloma before we start talking about the study?

Dr. Ghobrial: Absolutely. So the first thing we want to talk about is why would we be interested in focusing on MGUS and smoldering myeloma? And just for everyone to remember that every single patient who’s diagnosed today with multiple myeloma would have had an earlier precursor condition — MGUS (monoclonal gammopathy of undetermined significance) or smoldering myeloma — but they were not diagnosed with it because we don’t go looking for it, and we don’t diagnose people incidentally, or we don’t look for it until you have something — fractures, bone pain, anemia — and then you go to your doctor, and they find myeloma.

So one of the biggest questions is, well, what if we find it earlier? Can we prevent every single case of myeloma? In some people, you are found incidentally. You went to your doctor again, and he found a high protein level or some slight changes, and he looked for it. Instead of diagnosing you with active myeloma with end organ failure, they diagnosed you with an earlier precursor condition, MGUS or smoldering. But that’s pure luck. That was just incidentally you were found to have that.

So what we’re trying to do is we’re changing that idea, that by pure luck you were going to a physician who was able to find you. Why not actually screen for it and try to find it? And you start asking the question, well, why would we screen for it? And the answer is, if we can find it early, if we can detect every single case of myeloma at an earlier precursor condition, can we prevent it from going on to myeloma? Can we completely change the way we think of myeloma by early intervention, early interception, and you do not even ever result myeloma? And that’s the goal of this whole idea.

So we started a few years ago, the Center for Prevention of Progression, trying to see all patients who have MGUS and smoldering and even if we don’t see them, we ask them to join our study, which is the PCrowd study, precursor crowd, where they can send us samples, they can send us information. It’s basically crowdsourcing for patients, telling everyone you are empowered to give us your information and your samples so that we can find out how we can predict who will progress to myeloma and who will not progress to my normal. If we can say you have high-risk to go on to myeloma, then we offer you options of clinical trials. If you are not high risk and you will likely not develop myeloma in your lifetime, then that’s also very good news for you to know about and be comfortable with.

So then the next step is let’s start screening. Now, we know that in Iceland, they’re screening every individual who lives in Iceland, but the US is very different. We are very different individuals. We have different races, different international people. We want to get that sense of how does it look like here in the US or at least in North America. We wanted to ask a question – if you are at high risk of developing myeloma, meaning you have a first degree relative, your mom, your dad, sister, or a brother who has myeloma, you have a two to three times higher chance of resulting myeloma compared to a regular healthy individual.

The other thing is African Americans, as well as Africans, in many countries have a three times higher chance of developing MGUS or smoldering myeloma or overt myeloma compared to another individual. So if we look at everyone, as we get older, by age 15, we have a 3% chance of getting MGUS. That’s a very high number. Every one of us, once we start hitting that age, we have a very high chance of developing MGUS. That’s three times higher in African American, meaning if you’re aged 40 or 45, you’re already at the 9% chance. So a younger age and a higher incidence of developing MGUS.

So these are the people that we’re looking for, high-risk individuals. We’re asking them to go online and see if they do indeed have MGUS which is the PROMISE study, and they’d go on promisestudy.org, see if they are eligible, and then they sign up. It’s very simple.

Jenny: You just explained it, but I think for people who don’t live and breathe this all the time, I think they have to differentiate between these two different studies. So PCrowd is for MGUS or smoldering myeloma patients where you can send in blood samples or bone marrow samples. You don’t actually have to travel to Dana Farber to participate in this study. It’s this observational study. You’re studying people who already have MGUS and smoldering myeloma in that study and seeing who is progressing and why, and then you can keep track of people.

I think it’s an amazing study because there’s a lot of data that shows if you know you have even MGUS — and I would assume this relates to smoldering myeloma too — you actually do better if you develop active myeloma and probably because, what you were talking about earlier, you’re preventing the bone damage, or you’re intervening earlier. So you’re preventing the renal failure and bone damage and things like that by treating earlier.

And then the PROMISE study is for all African Americans, not just those with either a precursor condition or myeloma, and family members of people who have myeloma or MGUS or smoldering myeloma. So I think those two things are really important distinction to make. You talked about it, but I think it’s worth repeating because I think it can be kind of confusing sometimes for patients. There’s something for everybody, I guess, is the point.

Dr. Ghobrial: Yes. And thank you, Jenny, for explaining it because they are indeed sister studies, and they do complement each other. If you already have the diagnosis of MGUS and smoldering myeloma, you go to PCrowd and we will send you a kit that has information. When you go to your doctor, you get your blood tube drawn there. We ask to get your medical records every six months or once a year, whenever you’re going to your doctor or every three months.

If you are at high risk for developing myeloma or MGUS, meaning you’re African American or you’re a first-degree relative of someone who has MGUS or smoldering or myeloma or Waldenstrom’s, then you join the PROMISE study, meaning you do not already know that you have MGUS or smoldering. You’re seeing if you have it. In that case, you sign up, you fill a small questionnaire, and we also send you a kit. So that’s also online. It’s also nationwide. Basically, that kit, you take it to either a Quest Diagnostics or to your local phlebotomist wherever you go, and we will test you to see if you do have indeed a monoclonal protein or not, and we will call you if you are positive.

We expect, out of the 50,000 people that we are screening right now, to have about 3,000 positive. So the chances of being positive is very low, but we want to ensure that we can capture that information. I’ve been calling every station to tell them, indeed they have this positive case, or if they’re negative, then we send them an email saying, “You’re okay. You’re negative,” and then we will rescreen you again in three years. But the whole idea is that if you are positive, then we will also follow you up every six months or every year, depending on your disease status, of course, and help you prevent myeloma from happening.

Jenny: I’ve talked to you about this before on multiple ways, but for people who haven’t heard it before, just the idea of preventing this progression and why are you going to wait till you have active disease has really been a focus of yours. Do you want to just talk a little bit about that?

Dr. Ghobrial: I can tell you, and it’s a personal story for me because when you go to your primary care physician, as we start getting older, age 40 or 45, and you start screening for breast cancer, for colon cancer, you do a mammography, you do a colonoscopy, and the first thing I wondered is why are we not looking for blood cancers? It’s a simple blood test, yet we don’t do it. And even when we screen, let’s say that you have an early breast cancer lesion, your doctor will never tell you, “You know what, wait until you have metastatic disease and you have bone pain and fractures in your bones, and then I’ll treat you.” You never hear that, but that’s exactly what we do every single day for patients with myeloma. We tell them, you have MGUS, you have smoldering myeloma, why don’t you wait until you have fractures in your bones, anemia, bone lesions, renal failure, kidney failure, and you’re almost dying basically, and then we start treatment?

So it’s not a surprise that we haven’t been able to cure myeloma because probably we’re just waiting too long, and we’re waiting for the disease to be too much and then we start treatment. It’s a very simple question. What if we start treatment earlier? Can we prevent this from happening? Can we completely eradicate the disease and not have to have myeloma happening in the future? So it is very exciting for me because potentially we have the actual drugs, we have great drugs, but we’re just using them too late for our patients.

Jenny: Yes, that makes sense. So myeloma is, on one aspect, you could say, it’s hard to diagnose just because people aren’t screening for it. So people who have MGUS or smoldering myeloma or it’s progressing to active myeloma, you might be going to the chiropractor and have this back pain you can’t explain. I have lots of friends who have had those types of issues, and you go for multiple years and then you realize, “Oh, I actually have really active myeloma.” But it’s actually not hard to diagnose because there are specific blood tests that you can do.

I have a friend who has ALS, and myeloma is so much further along than that disease because you have these what they call biomarkers. You can test for it in the bone marrow. You can test for it in the blood. In a disease like that, there’s actually no blood test or no other tests you can do.

So in myeloma, we’re lucky that you can do this kind of screening study. It seems so obvious. Why wouldn’t you? It’s a simple blood test, and then you know, and then you can treat earlier. So I think it’s such a great idea.

Dr. Ghobrial: It is a great point, Jenny, because if you think of lung cancer, for example, it’s very hard to screen for it. You think of CT scans. For other cancers, there are no good markers, yet for myeloma, we have the perfect biomarker and it’s in the blood. It’s easy. One tube of your blood, you can get to know if you have a monoclonal protein or not. Not only that, but now we are using in the PROMISE study mass spectrometry which is a new test that is much more sensitive than the usual serum protein electrophoresis, meaning that we are much more sensitive in detecting whether you have a monoclonal protein. Indeed, many of our patients who we are calling right now are mass spectrometry positive, but they were not going to be detected by the routine methods.

This is important because we can detect it so early, so the chances of someone having early, early pre-MGUS sort of, their chances of lifetime development of myeloma is probably very low, but it’s also very good to know early, just like you said, because you can prevent it, because by knowing, knowledge is empowering you because you will go into your doctor. You will make sure you don’t have that back pain and low back pain and then never do anything about it until you have the fractures. You can look at other health information and make sure that you are aware of things. If we offer options of treatment that can prevent progression, whether it’s changes in health or diet or exercise or metformin or other things, potentially these could make a difference in your lifetime. So I think it’s empowering people to get that.

Jenny: And there are so many immunotherapies being developed also that the idea of treating some of these earlier — I think what you’re going to learn from this study is you’re going to be able to see who’s progressing, who’s not progressing, why are they progressing, why are they not progressing. And then as you potentially could use immunotherapies that have a very low side effect profiles to that can you develop this amazing strategy to determine first who is going to progress and who won’t progress. Can we talk about progression for a little bit?

Dr. Ghobrial: Yes, absolutely.

Jenny: And MGUS and smoldering myeloma? Just so people kind of understand just typical patterns of progression, like if you’re diagnosed with MGUS, is there a certain amount of time you can expect or rate of progression or at what percentage of patients might actually progress to active myeloma?

Dr. Ghobrial: Sure, absolutely. So the difference between MGUS and smoldering myeloma is the percentage of bone marrow cells, the myeloma cancer cells in the bone marrow. If they are less than 10%, then it’s MGUS. If it’s more than 10%, then it’s what we call smoldering myeloma. However, that distinction is also not perfect because the bone marrow is patchy, and there could be areas that are 9%, areas that are 11%. You personally did not change if your bone marrow has some areas that we can count as 9% or 11%. So that’s very important to know that it’s a continuous disease that goes on from MGUS to smoldering myeloma, and people should not be scared when the number comes up at 11% or 12% instead of 9% and say, “Oh, my, my numbers have changed.”

The second thing to know is MGUS’s rate of progression is extremely low. It’s a 1% chance per year, meaning every year you have a 99% chance of not developing myeloma, and 1% chance of developing myeloma. And that goes on every single year again, and that’s why we keep seeing everyone forever because the rate of progression can still happen even 50 years, 20 years, 30 years after. And because we know that every single myeloma that was diagnosed, so let’s say you’re 65 now and you have myeloma, likely you had MGUS when you were 45 and you did not know about it. So what if we can diagnose people at age 45 and get to know about it? You’re right, your chance of progressing to myeloma is extremely low, but it’s good to know that even years and years and years before that.

If you have smoldering myeloma, your chances of progression are much higher than that. It’s 10% per year. So in five years, you have a 50% chance of getting myeloma and a 50% chance of not developing myeloma in that time point. Now, all of these markers or all of these numbers were based on what Dr. Kyle has done for many, many years in Olmsted County at Mayo Clinic, and we’re fortunate to have real numbers, real data over the last 50 years being collected and for us to know those numbers. Other cancers may not know what the rate of progression of their numbers. So we’re very fortunate with that.

The other thing that we’re very fortunate with is that when Dr. Kyle called this MGUS, monoclonal gammopathy of undetermined significance, he really had the vision that potentially this can go on to myeloma even 50 years after. Originally, Dr. Jan Waldenstrom wanted to call it benign gammopathy, meaning it doesn’t turn into a cancer. It’s not going to be malignant. Dr. Kyle said, no, maybe even if it’s a 1% chance per year, maybe that can go on to myeloma. So let’s watch it carefully so that we can prevent it in the future.

That’s important to know why MGUS is important. Yes, it may look like benign things, it may look like it’s not cancer, but it’s precancerous and it has a chance of going on into cancer years and years from now. So it’s important to track it constantly.

Now, all of these markers are based on clinical parameters, meaning if your light chains are increased, if your monoclonal protein is high, meaning the protein that your cancer cells are secreting is high in your blood, or if the cells in your bone marrow, which are the cancer cells, are at a very high number, more than 10%, so if you start getting into 50%, then that’s a very high number, or if you have changes in your chromosomes that are bad, meaning bad cytogenetics, these are all things that can tell us that you are going to progress much faster to myeloma or not.

What we’ve been doing at Dana Farber, in collaboration with many other institutions, is we’re trying to get even better biomarkers to predict progression. We want to be more accurate in predicting progression for you. So we’re not saying you have a 50% chance. We’re saying you have a very specific chance as a very specific number.

To do that, we’re taking all of those research samples that you send us, the blood or the bone marrow biopsies from PCrowd or from PROMISE, and we’re doing something called next-generation sequencing, meaning that we can look at every single molecule of DNA and see if you have a very specific mutation there or not. So clinically, we don’t do that. We look at big pieces of chromosomes being damaged. But on the research level, and hopefully in the future, even give you back that information, we can see every single point of mutation, of change in your DNA or a change in your immune system, in your bone marrow, to help us predict whether you will progress to myeloma or not, and then we can tailor therapy, meaning we can improve our therapy based on this.

Jenny, you said it perfectly, if your immune system is a little bit messed up at MGUS or smoldering, could we give you a vaccine and prevent myeloma? Could we have a vaccine that suddenly myeloma is not there anymore, we’ve cured it by just a simple vaccination? And that’s the hope that we have for you.

Jenny: Yes, that would be totally amazing. Let’s talk about some of the study details. So do you want to talk about your study team members? Because just to give people relevance — Stand Up 2 Cancer is an organization that picks very well-established studies and well-defined studies, and they’re very careful about who they fund and invest into. This is one of those projects that they selected. They call it a Stand Up 2 Cancer Dream Team where they have investigators that are working together from different facilities who come together to do these large-scale big ideas, and this is a big idea.

So I just want to let people know that to be able to get the funding from Stand Up 2 Cancer is you have to have a great hypothesis and you have to have a great team in place to be able to receive this award. It’s a $10 million award to be able to process all these samples and do the outreach. So I just want to stress the importance of this level of study and support.

Dr. Ghobrial: The other important piece of it is we have great advocates like you on it who can tell us whether this is good research or not, and that’s very important. Indeed, Stand Up 2 Cancer really wants to make sure the advocates are informing us. So thank you for your help on that.

I can tell you our story. We were thinking of an idea for a screening study for myeloma for a couple of years before we applied to Stand Up 2 Cancer. We kept meeting and going through ideas and back and forth and discussing it. And then we said, “Well, there is this Dream Team application for Stand Up 2 Cancer. Let’s see if we can put our idea and see what happens.” I can tell you, I did not think they would take it because it was crazy. Who wants to do screening for myeloma? Who wants to fund 50,000 individuals being screened? No one would take that idea.

I could not believe is when we were invited to go and present. And then when they called me to say we were selected, despite amazing, amazing other researchers, of course, and that tells you that Stand Up 2 Cancer believes in early prevention and believes in early interception, that that can make a difference in cancer. In fact, I think all cancers right now at Dana Farber, we’re focusing specifically on early intervention and on early screening because that’s where you can make a huge difference to prevent cancer and to make a difference in curing cancer. So I think that’s an important mission statement there.

The second thing, you’re right, is the amazing researchers we have. We’ve been very fortunate, and I always say that I’m extremely lucky to work in an area where there are so many amazing scientists. That is just by osmosis, maybe you’ll get great ideas. So we have the Dana Farber, the MGH, the Broad Institute, Harvard Medical School, MIT, but also we have Hopkins, Mayo Clinic. We have collaborators also from many other institutions and not just from within the groups here. So we have other people in Emory, other people in Detroit Medical Centers, so many other collaborators who want to work with us and help us get to the level of achieving a difference for our screening study and to make a difference for our myeloma patients.

Jenny: Well, it’s really amazing. Let’s talk about some of the specifics because we talked a little bit about why you’re doing this study. We’ve talked a little bit about the two different groups that can participate. So maybe you want to go back — I know you mentioned this a little bit at the beginning but in a little more detail for people, just outline the steps. What does it take to join this study and participate in this study?

Dr. Ghobrial: Absolutely. So the first thing is, if you have a first-degree relative who has myeloma or MGUS or smoldering or Waldenstrom’s, you would be eligible, or if you’re African American, period. You don’t have to even have a relative who has myeloma. Just because you’re African American or of African origin and you’re over the age of 40 but not above age 75, then you’re eligible. If you’re not sure, just go on promisestudy.org and see if you’re eligible or not. It’s that simple. On promisestudy.org, we tell you exactly the details. We give you information. So you go online, you check it, you see if you’re eligible, and then you fill a questionnaire online. That prompts us to send you more information, which is another questionnaire, as well as a kit that arrives to you within a week or so, and that kit has information where you can go to a Quest Diagnostics lab or to any other lab that you wish. Let’s say that there is no Quest Diagnostics close to you, but you’re going to your primary care physician. Why not get your blood drawn there?

That kit has three tubes. One of those tubes will go to Mayo Clinic, and you don’t need to do any of it. The labels are in there. The FedEx labels are inside. The boxes are already pre-labeled. You don’t have to do anything. It’s pre-done for you. Quest Diagnostics are all trained to understand how to do that. So one of those tubes will go to Mayo Clinic, and the results come back to us, telling us if you do have monoclonal protein or not. That’s done either by serum protein electrophoresis or serum free light chain or by the new method, mass spectrometry.

If we see that your result is positive, we will be calling you to say, “Mr. Jones, you have a monoclonal protein. It’s likely MGUS. We need to refer you to one of the local oncologists in your area who can help us assess you more and get more information.” And then we call that doctor and inform him, “Mr. Jones is coming to see you, and he has this protein level elevated by our research sample. We would like to get you to do more testing,” meaning more blood tests and potentially a bone marrow biopsy to confirm the diagnosis.

If the level is very, very low, we may not want to do the bone marrow immediately and want to just have you follow up that doctor every six months or every year and so on. If the level is very high, let’s say it’s smoldering myeloma, then, of course, we want you to be seen more frequently and get a bone marrow biopsy. If the numbers are negative and there is nothing at all, then we will send you an email saying, “Mr. Jones, you do not have a monoclonal protein. We would like to screen you again in three years.” And the reason for that is potentially we may find that monoclonal protein again in three years.

Now, one of the biggest benefits of also checking on PROMISE study is we can detect something called amyloidosis. This is one of the worst cases. It’s the cousin of myeloma. What happens is it looks exactly like MGUS, but it affects your organs, meaning your heart or your kidney, and it can cause actually much, much worse survival than myeloma. People die faster usually with amyloidosis because it damages the organs. It damages your heart and your kidneys by making the protein stick to it.

The interesting thing about this screening study is it will also screen for amyloidosis. So think of the potential benefit not only of finding out whether you have MGUS but potentially finding out if you have early amyloidosis, and can we treat it early to potentially prevent it from happening? I think that’s crucial because that will change significantly the survival of amyloidosis. So we’re hoping that that will be a significant benefit from being on the PROMISE study and on screening early for MGUS or for amyloidosis.

Jenny: Oh, that’s huge. I think that’s very huge because some of that can be treated if you find out early, and there’s not too much damage, right?

Dr. Ghobrial: Correct, before your heart is damaged and your kidneys are damaged. Exactly.

Jenny: So the earlier you find out, the better. Let’s talk about for a minute some of the emotional aspects. So if you’re joining this study, there are some people who kind of look at life like, if I don’t know, then it’s not real. If I don’t believe it’s true, then it’s just not happening. But I take the totally opposite approach to life, where you should know because then you can be proactive and do something about it, and then you don’t have to be worried. You can go get tested. If you don’t have it, then great. You don’t have it. And if you do have it, at least you know it’s on the radar for your doctors. So have you run into anything that you have found to be helpful for patients dealing with that kind of choice about should I join a study like this? Should I not join a study like this?

Dr. Ghobrial: Yes, it’s a great question. It’s the anxiety of knowing something and then knowing that I have a precancerous condition and how to deal with that, especially the word cancer is so scary for so many people. So I think the first thing that you said is right. You have the power, you’re being empowered by knowing early. Remember, this is a precancerous condition. This is early detection of something that may go on to grow into myeloma years and years from now or may never grow into myeloma, but knowing about it can make a difference in your survival.

I think, in general, all other cancer screenings have made a difference in the survival of people. Think of breast cancer, colon cancer. If you find a small polyp when you do colonoscopy, you’re not scared of doing the colonoscopy. You’re hoping the doctors find it early and treat it early. So the same is true also for MGUS. If you get to know early, that’s actually good news because you can potentially prevent it from going on to myeloma. I think that’s important to know. The other thing is to know that it takes years and years for it to go into myeloma. This is not a sudden cancer diagnosis. This is a precancerous condition, so not to have that anxiety related to it is very important. But I understand how hard it is for everyone, and it takes a will and an interest in yourself, in taking care of yourself for you to be diagnosed and for you to get that blood sample done.

Jenny: I think the important thing about this, when you talked about steps to participate, is you’re not traveling. You’re just doing this in your city or someplace close to your house, or you’re just going to a lab that’s close to your house, and you’re just getting this done. So it doesn’t require very much effort on your part to participate. It’s easy to do, and you’re contributing to a potential cure for a lot of people. So I think there are a lot of positive emotional benefits to it too that you can be part of a solution.

Dr. Ghobrial: Absolutely. And it’s not just for everyone else, but it’s truly also for yourself, like you said. There was a study in Iceland where they said, if you knew that you have MGUS, your survival is usually better because the physician is following you so carefully. They will not wait for you to have a fracture or a kidney damage or anemia. So by knowing that you have MGUS and following up, you likely will have a better survival even if you don’t do anything about it.

Jenny: Right. I know it’s early on since you really launched the study and started inviting patients to it because there’s this ramp-up process that you have to go through to get all the processes working smoothly and everything. But have you learned anything so far that you can share?

Dr. Ghobrial: I can share some stories that have really empowered us all and made us feel so happy to have started that. So over the last few months, as you know, we launched this very slowly first, and then we allowed everyone to come in. We just wanted to make sure that everything works well. We have over a thousand individuals who have signed up. We have over 20 or 25 patients who are positive, and we called all of them, of course.

I can tell you, there were so many amazing stories. Annie, who gets the calls — first of all, our team here are just beyond amazing. They’re on call all the time. I think we had to tell her that at midnight when she’s brushing her teeth, she doesn’t have to be calling back with patients. She has an online system constantly getting the messages from the patients or the individuals who are calling to ask questions. She has a group of janitors who all wanted to sign up together. They didn’t want to go alone. They wanted to come as a team and just sign up together as a team. She had people calling from Alaska, and the shipping of that kit had to go through three or four different planes to get all the way to that tiny little city in Alaska.

She had amazing stories. One of our very first African American positive patients who we called a few weeks ago, her sister was diagnosed with myeloma, and she was undergoing stem cell transplant. They are seven siblings, and they’re so strong that she said, “I’m going to be tested, and my sister will be tested, and all my brothers will be tested.” She was positive, and we called her, and we’re going through talking with her and making sure that she gets into the system with a physician. But her other sister was also positive. They’re so strong and they said, “We want to tell everyone and we want to help everyone get early detection.” They want to encourage their brothers to go and get tested.

So it’s amazing stories from so many people that tells you this really hopefully will make a difference in their lifetime and hopefully will not be something that we’re giving them a bad diagnosis, but we’re actually telling them, here’s a precancerous condition, being careful and watching for it, and potentially preventing it from happening or going to myeloma is important.

Jenny: That’s amazing. Well, let’s go over the age requirement again because when I initially heard about this study, I called my entire family and I said, “You all have to go get tested.” My parents realized that they were over that age requirement. So it’s 40 or 45 on the low end?

Dr. Ghobrial: Yeah, so we just changed it from 45 to 40 because we had so many phone calls of I’m 43. I’m 44. Can I join? I’m 41. Can I join? We’ve noticed that the studies with African Americans, even at age 40 or above, puts you at risk. So we’ve changed the numbers to 40. We kept the higher number to 75 just because after age 75, we felt that maybe that won’t make a big difference when we start early vaccines or early treatment interventions to prevent something that will happen 20 or 30 years after. So that’s why we put an upper limit, but that’s something that we can discuss if someone is 76 or something like this. We also will likely extend it to Canada and just open it up and not just in the US. So that will be something else that will be changed soon. And then we will invite all our Canadian colleagues and health individuals to join.

Jenny: Oh, that’s wonderful. Well, I’m still going to invite my sisters to join. So for me, this is kind of like — I grew up in the ’70s. Do you remember the Faberge commercial? And you tell two friends and they tell two friends and so on and so on. So maybe you are the Heather Locklear of myeloma. If we invite, every one of us knows someone who’s African American, and every one of us probably knows a family member, if we’re involved in myeloma at all, that could participate in the study

So my challenge to all of our listeners and to everybody that’s associated with the myeloma crowd is to invite two people to participate in this study, and then kind of like the ALS Ice Bucket Challenge, pass it along and invite them to invite two people to this study because I think if we do that, it will not be hard to have people do these studies.

Also, I know you’re coming to some patient meetings and actually taking samples there. Do you want to talk about that a little bit?

Dr. Ghobrial: Yes. So we’re starting soon to have two of our researchers, our team, who is working here on PROMISE to come to many of the meetings, to have with them kits, and potentially in some areas to have a phlebotomist right there. And we will have iPads or tablets where people can just sign up on the spot. It takes five minutes to sign up. And then either we will give you a kit with your number on it, or if we have a phlebotomist, we’ll go ahead and get your blood drawn immediately. So look for a booth with our name, promisestudy.org, on it. You’ll find people, hopefully, everywhere where there is a myeloma meeting, there is a myeloma run. In the International Myeloma Workshop next week, we will be there. So again, if you don’t find us, also let us know. If you have a small meeting with small group of people who are gathering together, please let us know and we’re happy to come and inform you about it.

Jenny: Okay. They can contact you for that, or they can also contact me and then I can pass it along to them for that.

Dr. Ghobrial: Absolutely.

Jenny: There has been a lot of research coming out. It seems like — well, it’s probably older because you mentioned that it existed before. It talked about the genetic evolution in smoldering myeloma. But I just read a paper that was talking about smoldering myeloma and like how the genetics of the disease evolve over time. So maybe you can address that a little bit. And then I have another follow-up question that’s about something outside of just the genetics of the disease.

Dr. Ghobrial: Sure. Again, it’s not very well known yet how clonal evolution happens in smoldering myeloma. We still have a few more studies to be done on that. But basically, what happens is, our cancer cells don’t all have the exact same changes. They don’t all actually look like sisters and brothers of each other. They start to have differences between them so that you have multiple clones or multiple subgroups of cells that look alike. By the time you’re diagnosed with myeloma, you probably have five or six different subtypes already of myeloma within the same cancer that you have.

Now, how do they grow is hard to know which one comes first, and then how do they compete with each other and why would one take over the others is also a lot of questions that are being asked right now. But what we think happens is your normal B cells and they mature to become plasma cells, one of them gets to change, for some reason. Maybe it was growing in response to an inflammation or an infection or immune changes. Those cells, as they’re growing, they get a small error, a mistake. That’s usually a mutation. And that leads to further changes, and then there are either big chromosomal changes, so big pieces of your DNA and so on. You may have enough of those cells when you have MGUS.

Now, further changes happen and again, we still don’t know why and how they happen. But then you start acquiring more and more mutations or copy number alterations or chromosomal changes that make the cells able to grow much faster and compete with the other ones that don’t grow as well. At the same time — and we’re still now understanding how that happens — your immune system starts to not work very well and cannot recognize anymore those cells as bad cancer cells. So they shut down the immune system, and now they’re able to grow more and more. By the time they get to myeloma, they’re starting to eat the bone or cause anemia because they’re compressing on the bone marrow cells, the normal red cells, or they’re secreting enough of those antibodies, the light chains and the heavy chains, to make the kidneys not work well.

So all of those different steps are steps for us to potentially intervene. Can we prevent it from acquiring more hits? Can we improve on the immune system? Can we make your immune system recognize the cancer cells early? Can we understand which mutations lead to progression? We already know, on our own data set, as well as studies from Dr. Bergsagel at Mayo Clinic and others that MYC alterations are very important for leading to progression of myeloma.

So if we detect MYC in your case, can we say this patient is likely going to progress to myeloma? That’s already a genetic marker that can predict progression. We have other markers. MAP kinase mutations like KRAS and RAS, DNA repair mutations, all of those can predict for us, as well as big pieces of cytogenetic changes like 17p, p53, 4;14, 14;16, and so on. These are all markers that say your cells are working faster and growing faster and are able to get into myeloma much faster.

Jenny: And then I saw at a recent myeloma meeting, and one of the doctors was talking about smoldering myeloma genetic progression. They were saying that when you have kind of the same clone that you had when you were at diagnosis and it kind of stays the same, you might actually progress faster from smoldering myeloma to active myeloma versus the development of all these different clones because maybe they’re just trying to get ready to grow but not ready to grow. I thought that was kind of interesting. I don’t know if you have any comments about the types of progression and that connection.

Dr. Ghobrial: So in this study, a whole genome sequencing was done on samples of people who had smoldering myeloma, and then they progressed to overt myeloma within six months or a year versus those who had it progress in six years or five years. The ones that there was a difference between the two bone marrow biopsy times of five years, there was an early clone. By the time you get myeloma, you have multiple other different clones, meaning you acquired new mutations or new changes while the ones that were only six months apart or one year apart looked very similar and all it had is expansion of the prior clones.

Now, it’s hard to know what that means. It potentially means that when we get that first smoldering myeloma sample, if you already have the bad guys and that’s for a sample, that all they need is expansion and they don’t need to do anything more than just grow faster. If you don’t have those early bad hits in your first sample of smoldering myeloma, then likely you will not progress fast. It may take another time point that we did not get during that research study to acquire that second hit, and now you get that expansion. So I think it’s a function of bad things just grow faster, and the ones that are not bad will be acquired later on, potentially.

Jenny: And that’s why you’re going to do the next generation sequencing on people who test positive, right?

Dr. Ghobrial: Correct. Exactly. Absolutely.

Jenny: Yes, that’s great. I know you’ve done a lot of work on the bone marrow microenvironment and the interplay between all these different types of cells and what’s keeping it down, or what’s letting it grow. There’s work being done now, I guess, on the microbiome, so how effective is that? Will you end up learning more about that piece as well? Because Dr. Anderson at Dana Farber just said, when we’re just looking at genetics, we’re just looking at half the story.

Dr. Ghobrial: Yes, absolutely. Ken is always right saying it’s in the neighborhood. It’s true. It’s a microenvironment as well as the macro environment, meaning the big things that are around us. There are so many things that affect us and affect our immune system. It’s not only the food we eat or the microbiome that we have in our gut that can affect our immune system, and then potentially affects cancer and how it grows. But there’s also obesity, diabetes, stress, the type of food we eat, the type of interactions we have and, of course, the environmental exposures that we have, pesticides, insecticides, living near a farm, or all of these things affect the immune system as well as affect the genetics that we have.

So there is so much to be learned. The PROMISE study is doing a lot of those. So we have a whole questionnaire on epidemiology, on where do you live? Do you have exposure or not? Are you diabetic? Are you overweight? Are you changing your diet suddenly? We are going to start doing a microbiome tool collection. We are going to add a lot of this information so that we can link the genetics to the immune system, to the microbiome, to the macroenvironment of health, diet, nutrition, and all of that.

Jenny: Nice. Yes, that’s fantastic. Well, when you look at it holistically like that, I think is just terrific.

Dr. Ghobrial: Well, we’re excited. We can only be successful if every single person, like you said, joins us but also tells two or three other friends or family members to join us.

Jenny: Yes, they tell two friends and I tell two friends and so on and so on. That’s going to be our new mantra for the study. I think it’s such a great study. I want to leave some time for some caller questions unless there’s anything else you want to discuss first?

Dr. Ghobrial: No. I’m ready for any questions, Jenny.

Jenny: Okay, great. We have a few callers.

Caller: Hi, Dr. Ghobrial. I just have a quick question. You mentioned the mass spec test earlier. So I just want to know, do you know how many hospitals are using this new technique, and why it’s so much better than the electrophoresis test?

Dr. Ghobrial: Yes. We are doing it now in collaboration with Mayo Clinic and Binding Site. I don’t know that too many other centers have it yet, but it is actually approved and it’s covered by many insurances although not all of them yet. Mayo Clinic is definitely the place to ask them or Binding Site, and they can let you know if there is a mass spectrometry machine available in other centers.

Why is it more sensitive? Because it’s a newer technology that can detect small amounts of protein, much, much more sensitive than the old protein electrophoresis method. So just like every technology that keeps improving, the TV that you had or that we had 20, 30 years ago is very different than what we have right now as well as our phones. It’s the same for protein detection. What we can do now is much, much more sensitive than what we used to do with the regular protein electrophoresis.

Caller: Okay. Yeah, that makes sense. Thank you so much.

Dr. Ghobrial: Absolutely. Thank you.

Jenny: Okay. Go ahead with your question.

Caller: Hi, Jenny. Hi, Dr. Ghobrial. It’s Dana Holmes. It’s so great to listen to the two of you chat today. I’m just always so fascinated to listen in on Jenny’s radio shows, and they are just the best. So thanks for taking my call.

I really just want to say and encourage anyone who has been diagnosed with MGUS or smoldering myeloma to run to their computers and sign up for the PCrowd study. It is one of the best things that we can do for our anxiety. I have been there. I have done that.

When I was first diagnosed, I was horrified as I was reading information online. I truly felt paralyzed all for about a week. And then I shook myself off and said, “Well, this is no good. I really need to learn what I need to learn about this disease.” I just kind of moved forward from there. As soon as I heard about the PCrowd study, I said this is for me because I’m not eligible for any early treatment clinical trial. So what was I doing? Sitting, waiting, wondering, worrying. This empowered me to feel that at least I’m providing you guys with the tools that you need to answer the questions that I have, that being am I going to be the type of patient that eventually progresses to myeloma, or can I hope to live to be a grandmother sitting in my rocking chair with a bunch of grandkids sitting around me?

So I really want to encourage people. It really, really, truly does empower you. And it’s the easiest study to participate in. So that said about the PCrowd. I don’t have any family members that are eligible for the PROMISE study. But, boy, what a study this is too. This is going to also give additional answers. I did a little dance when you mentioned that you guys are going to be screening for amyloidosis as well. I think that’s so amazing because we have people in our smoldering and MGUS groups who are underdiagnosed for that condition. It’s really, really sad because they go underdiagnosed for so many years and develop the organ damage. It really could have been caught a whole lot earlier had somebody just thought about it. So I was really tickled to hear about that.

I just had a question today from somebody in one of the groups whether or not you’re going to be doing this in Canada. So I was happy to hear that you’ll be extending it to the Canadian patient population as well. So that’s really, really terrific. So I really want to thank you for all of that. I do want to ask for your help to have some understanding for a patient who sits and worries about their children who may end up having this condition pop up somewhere along their lifetime. How are you actually sorting through and figuring out whether an MGUS patient, a mother who has myeloma, would eventually progress as well?

Dr. Ghobrial: So again, Dana, it’s always amazing to talk to you and to hear you talk because you are truly an ambassador for us. It’s your excitement that’s really infectious to all of us. So thank you again for all of your encouragement. You really hit it on the nail for so many of those points of the anxiety of what am I doing and should I be doing anything? Just contributing even to reach samples empowers patients and empowers everyone to be participating. Yes, you’re right about Canadians as well as other members.

Now, the part of family members, it’s very important. What we’re doing and the PROMISE study is we’re not only looking at the tumor cells or the microenvironment. We’re also doing something called germline sequencing, meaning we are taking your own normal DNA, the one that you were born with and sequencing it so that we can understand better why are certain people susceptible to develop myeloma or not.

And then from there, we’re looking also at their own tumor cells and asking the question, well, if you inherited gene x from mom or dad and mom had myeloma and you develop MGUS, will you also acquire the same mutations and the same changes? Will you result myeloma earlier or not? I don’t think that the answer is well known yet. In fact, when we look at the African American population, when they develop myeloma, it doesn’t behave any worse than anyone else like a Caucasian who develops myeloma. The survival is worse because they do not get access to drugs early. They do not get into therapeutic options early. That’s different. But if you were treated the same way, you would like to have the same outcome. As far as biology is concerned, the types of myeloma may not be worse.

So that’s good news. We just need to have bigger studies. Hopefully, the PROMISE study will answer that question of understanding risk for germline sequencing, risk for immune and other susceptibility genes that lead to progression, epigenetic regulation of the immune system or epigenetic regulation of the tumor cells. All of these are unanswered questions. And then, of course, whether you would progress faster or the same issues result myeloma and you have a family member.

Caller: That was very, very helpful. Now, can we talk about bench to bedside? Are we closer to the bench, or are we closer to the bedside with the information that you guys are actually gleaming from even the PCrowd study? Because I’ve been doing the PCrowd study now for four years. I’ve donated 16 serum samples, I’ve donated two bone marrow samples. It’s important to me because, otherwise, my option is sit and say, “Gee, what are these guys doing? Why isn’t there a cure? Why don’t they figure this stuff out?”

Well, we need to help. As patients, we need to give you our tissue samples, our serum samples, because then you can take it into your lab and do all of these wonderful tests. So from a bench to bedside, what is it going to really — or bedside? Is it bench — yes, it’s bench to bed bedside is the term. What do patients, what do we need to do with the myeloma and MGUS and smoldering community to help really push this type of research forward?

Dr. Ghobrial: So I can tell you it goes both ways, bench to bedside and bedside to bench side. It’s both ways. That’s the beauty of translation, meaning we can do both and we can understand both because we learn also from patients and from clinical trials. But from bench to bedside, PCrowd has already helped us understand which mutations can predict progression. We’re still working on more but already MYC alterations, MAP kinase mutations, certain cytogenetics, as well as DNA repair genes are well known from the clinic. We know that certain clinical trials give us long response. So we’ve initiated multiple clinical trials, and some patients actually progress after being off therapy, and those people had certain mutations or certain changes that predicted for us now that they will be the faster progressors.

Based on just even that data, we’re already designing the new trials so that we make sure that certain patients who have certain abnormalities, we will give them a specific treatment. We’re trying to model the treatment for smoldering myeloma in a completely different way than what we usually do for myeloma, meaning we will try to use the genomic information and the microenvironment information so that we can peel our therapy and have precision medicine for smoldering. Not everyone should get Elo-Rd or KRD or RVD. But actually, if you have 11;14, you get something specific. If you have a p53, you have something specific. If you have a very low risk and you have certain new antigens, you get the vaccine, and not just everyone gets the same treatment.

Caller: That’s fascinating, Dr. Ghobrial. It really is. I thank you for your research. Jenny, I know I’ve eaten up a lot of your caller time, so I will say thank you to both of you and have a terrific day. Thank you.

Dr. Ghobrial: Thank you.

Jenny: Okay, thanks, Dana. Okay, well, Dr. Ghobrial, thank you so much for joining us on the program today and for just sharing about this really important study. I think it’s going to tell us a lot about progression and I don’t think just for smoldering or MGUS patients, I think just for everybody that has active myeloma. It might influence what we learn about why people relapse after therapy as well. So I just think it has really broad appeal for everybody. We should all be encouraging our family and our friends and our African American friends to join this study just because it’s just so important.

Dr. Ghobrial: Well, thank you so much, Jenny. We really appreciate all your efforts and all your help.

Jenny: We’re happy to do it. This is something that patients can contribute, like Dana was saying. I think this is an important way that patients can contribute to our own cure, and we should do it. So thank you again for joining, and I thank our listeners for joining and 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.

22 Comments

  1. Sherry Keck October 2, 2019 at 6:08 pm

    How do I participate in the Promise Study? Have had Smoldering Myleoma for 3 years, would love to participate in study.

    • Jenny A
      Jenny A October 2, 2019 at 9:30 pm

      Sherry, your family members between the ages of 40-75 are welcome to join this PROMISE study. For you personally, you should join the PCrowd study. This is for MGUS and smoldering myeloma patients. https://pcrowd.dana-farber.org/

  2. Paul Dodd October 3, 2019 at 12:19 am

    The link JOIN THE PROMISE STUDY seems to be broken, I get oops! Page not found

  3. Angela Willis October 3, 2019 at 2:31 am

    How do I join the study? When I access the link an error message is returned. My mother had Multiple Myeloma and passed away in 2017. My youngest brother has already been confirmed to have the gene but the remaining 7 of us (siblings) have not been tested for the gene. It is VERY important to me to be a part of the study. Not just for us but for future generations.

  4. Aurora Monroy October 3, 2019 at 6:45 am

    Is this trial only for people who have myeloma. My mother passed away in 2013, lived 5 years with multiple myeloma.
    Can I have my doctor to test me for any signs of myeloma.

  5. Marie Jenkins October 3, 2019 at 1:33 pm

    Wish this was available to me I’ve had MGUS for 25 yrs. Developed mantle B Cell Lymphoma last year. 6 mos chemo now my protein count has risen and they are not sure it’s myeloma or lymphoma. I am a Hopkins patient.!

  6. Marilynne Roche October 3, 2019 at 6:29 pm

    Wonderful presentation as always Jenny. Thank you Dr. Ghobrial. These two studies sound amazing! I will encourage my three daughters, as children of a mother with myeloma who is the daughter of a father who had myeloma, to participate. Thank you for this opportunity.

  7. Carol October 4, 2019 at 9:35 pm

    Very interesting. I’m a lynch syndrome person so most forms of cancer are a possibility. Thanks

  8. Christine Bradley October 8, 2019 at 8:31 pm

    This is very exciting news! I was diagnosed with SMM six years ago and luckily remain in remission four years after an ASCT. I live in Canada and would like my two sons and my five sibs one being my twin to take part in the Promise study. How will I know when those of us in Canada can start registering for the study? Thanks for taking on this very important study so we can get closer to a cure of this complex and deadly disease.

  9. Lynn Caldwell October 8, 2019 at 8:32 pm

    I signed up for this study and I have not received any correspondence.

    • Jenny A
      Jenny A October 9, 2019 at 9:48 am

      Lynn, I passed your email along and they will be reaching out.

  10. Carmen Standiford October 9, 2019 at 8:29 am

    I think it’s interesting I was diagnosed in jan with advanced MM with the chromasone changes and make all light chains. To be this advanced I had to have had it for a long time therefore having it in my early late 20’s. I am not African American nor do I have any known relative to have had MM. Yet I never qualify for studies. Why do I have MM? Why do I make all light chains? Why seems to be of no importance to any study. Yet my case is really a big question that might help research in a big way.

    • Jenny A
      Jenny A October 9, 2019 at 9:59 am

      Carmen, if you want to learn more about myeloma and find others like you, I suggest that you join an online tool we created called HealthTree (www.healthtree.org). Soon you will be able to find your genetic “twins” and see what they had for therapy and how they responded. We are also building a comprehensive “university” for myeloma with over 30 courses and 600 lessons from 75 myeloma experts.

  11. Tayne October 10, 2019 at 2:03 pm

    This was very interesting. Altho my children are too young and my dad is too old, it is still interesting.
    I had MGUS at 55, for 2 yrs before turning into MM at 57. I am a Caucasian female and was told not to worry the percent was so low that it would turn into MM. Was told after my next visit I was going to be push back to 6 mths. But before 3 mths pasted I developed bone lesions. Broke bones and calcium so high I don’t remember close to a week in hospital. I am in remission now after SCT but hope they find a cure soon.

  12. Jeanne Carver October 11, 2019 at 6:19 pm

    I just wanted to let you know that my husband died in 1997 from Multiple Myeloma. He was diagnosed in February and died in November. He was in Vietnam and we always figured that had something to do with it. He also did construction work. It is a horrible disease.

    • Jenny A
      Jenny A October 14, 2019 at 10:37 am

      Jeanne, I am so sorry to hear about your husband. I think Agent Orange is the likely cause. This is a terrible disease and we are doing what we can to find a cure. All blessings to you. Love, Jenny

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