Hello everyone and welcome to our Facebook Live for the International Myeloma Foundation. As today being September 1st, we are kicking off Blood Cancer Awareness Month. We're delighted that you've joined us today here online, so for the next half an hour, we're going to be spending time with Dr. Joe.
My name is Dr. Joseph Mikhael, I'm the Chief Medical Officer of the International Myeloma Foundation. For short, I get called Dr. Joe, it just makes it easier because Mikhael can be confusing to people. I know it's Friday, and Friday evening before the long weekend, but kick off your barbecue, flip your veggie burgers or your real burgers or whatever it is you're doing, and hunker down to hang out with me over the next 30 minutes as we talk about research in multiple myeloma. Now, before we get going, a couple of things. As I mentioned, today is September 1st, so it kicks off Blood Cancer Awareness Month, and we've called this know myeloma and it's a bit of a play on words, know myeloma, and you can read all about it at knowmyeloma.org.

But of course the two middle letters in no is know is N-O, and we want to say no to myeloma. We don't want myeloma to do tragically what it has done for decades and years for so many people and taking their lives and robbing them of their quality of life, but we at the IMF are committed to curing this disease and committed to supporting patients through their journey with this disease, and as you're going to hear today, we talk about research, massive advances in this disease. Really there's perhaps no other cancer that has seen the tremendous progress that we've seen in multiple myeloma over the last decade where when I started myeloma 20, 25 years ago, most patients didn't live a year literally, sadly, with the disease. It's one of the reasons why I went into the disease, but now we see people living so much longer.

Join in the chat because the point of this is for me to answer questions about research and I'm happy to see people joining, thank you for coming in. What I'm going to ask you to do is, jump into the chat box and you can put your questions in, but for these first minute or a few minutes, put your name in, tell me who you are, tell me where you're from so I can get to know a little bit of the people that are joining in. I see more and more viewers are coming in every few seconds, so please let me know who you are because, one, I like to know who's there, but also... Thank you, already, Brittany's already jumped in with a question. I'll come to your question in a minute, Brittany, because it's an excellent question.

But also there is a chance, I don't want to get too cheesy on you here. I don't want to get too car salesman like, no disrespected car salesman, but we do have some free swag for you in light of Blood Cancer Awareness Month and in light of how we are really trying to raise awareness around myeloma. We have some t-shirts, we have hats, we have some laptop cases that the IMF is distributing out, and I have been given Pentagon clearance from the IMF to give out some of this swag tonight based on the brilliant questions that I know people are going to be asking, so please have the opportunity, not that you're asking for the sake of swag, obviously this is a serious disease and we want to understand it better so we can tackle it and care for our patients with it, but we thought it would be fun. Who doesn't like a little bit of swag that we'll hand out as we go?

Thank you Anita Marie is telling us that she's here from Maryland and even that she had a bone marrow transplant a couple of weeks ago, and you're online with us, thank you, god bless you. I love that you are engaging even that soon after a treatment. I see that Brittany is from South Dakota, so we're already starting to cover the map. We've got Jason from Orlando, we've got Kim who is a caregiver from Alabama.

Welcome. We mentioned Charlotte, North Carolina, one of the areas that we've been doing a lot of work as the IMF, so this is great. I am happy to see all these folks joining in. Susie just joined us from Tennessee. We have Anna from Brazil. All right, let's expand this portfolio. We've got Mary from Pennsylvania. We have Lucy from Toronto, from the Motherland. I was born and raised in Canada and lived in Toronto for many years before coming here to the US, so Lucy, bonjour, and welcome. I've got my BFF, Steve Weinstein has joined us here. Steve, nice to see you're typing and knowing that you're coming to us from Florida, of course. We've got someone from Southampton in England. We've got Louisiana. Oh my goodness, we are pretty much covering the map here. We have another one from England. Thank you for joining us.

It's a little late there, so thank you for staying up late to hang out with Dr. Joe. Excellent. Well, we are both at the five-minute mark, so I think we want to get rolling here into the questions. I'd love you to begin to ask questions. Let's start here with Brittany. You were the very first one to send in a question. This is one of my favorite questions, so I think Brittany might just have earned herself a little bit of swag here. It's a challenging question, but it's one that I think I'd like to spend a couple of minutes answering as we think a little bit about how myeloma impacts families, and just before I answer your question, Brittany, which is, is multiple myeloma hereditary? Let me just remind everybody that research is fundamental to what we do in cancer and in so many areas of medicine, if it weren't for research, we would not have the drugs that we have now and the processes that we have now to improve the lives and extend the lives for our myeloma patients.
I know that the history of medicine has terribly, unfortunately dropped the ball at times when it comes to research, and sometimes people are very put off by the concept of a clinical trial because of our history. I do a lot of work in health disparities and underrepresentation of minorities in clinical trials, so we know tragically whether it's episodes and histories like Tuskegee and others where we know that people were terribly treated, but thankfully we have so many more protections against that now and we have an opportunity to really help individuals, and so we want to do everything that we can to improve the lives of patients.
At the IMF research, is one of our four major pillars, and that's why for Blood Cancer Awareness Month, we are profiling research for this whole first week. You're going to be seeing in our posts and seeing in our interactions that we're going to be focusing on research this month. For those interested, we're going to have several other Facebook Lives later this month, three actually, others, and I'll mention them at the end, but we will go to the other pillars of the IMF of education, of support of advocacy, and we're even going to have one on fundraising with one of our amazing IMF staff.

Let's start answering these questions. Some of them are directly research related, so feel free to answer, to ask other questions, but we really want to focus on ones that have to do with myeloma research. Several have come in already, but I promised Brittany I would ask hers. Is multiple myeloma hereditary, meaning does it run in families? The simplest way to answer this question is, generally speaking, we don't think of myeloma as a familial disease, however there is a component of it. What I mean by that is, for most patients that we see with myeloma, we're not routinely screening family members or looking for myeloma elsewhere within the family, but we do know that there are clusters of families across the country and there is a bit of an increased risk if someone has myeloma, and some of that is because we look for it, you find something, but some of it is indeed a genetic.

We haven't been able to unlock all of this, we're working very hard to understand it. One of the huge research projects that the IMF is involved with is the Iceland project, as many of you know where we've screened over 85,000 individuals in the country to better understand the genetics of myeloma, because these patients, many of them have already had their genome sequence, meaning we already understand the essence of their own genes, of their own DNA, and we can look to see are there patterns, are there clusters that result in more people having myeloma or not?

Pragmatically, what it means today is, a good myeloma doctor or oncologist should ask if there's anyone else in the family with myeloma or related diseases like amyloid or Waldenstrom's or even lymphoma, and sometimes there can be a strong family history and it may cause us to search a little bit more within that family, but this is really a hot area of research that we want to understand better. It actually points me to another area of research like I talk about all day, but I won't. But just briefly mention that we are trying to evaluate, is it time to think about screening certain populations for myeloma? Right now we look for myeloma when people have signs and symptoms consistent with myeloma. Tragically the pain, the fatigue, the low red blood cell count if it was tested, are often the things that point us in the direction of myeloma, and that's not considered screening because you're testing someone based on a symptom that they have.

Screening means you're testing someone based on no symptoms just because they're of a certain age or gender. For example, we do screening colonoscopies when people reach a certain age, or we do mammograms for women at a certain age. We're not at the stage where we're screening yet for multiple myeloma, but it is something that we are considering based on, as we know, certain populations that are at highest risk, which includes myeloma being twice as common in the African-American population, and so hopefully that answers your question, Brittany, because it's indeed a very good one.

Here comes some other questions. Oh, by the way, we've got some folks from Vietnam. That's fantastic, welcome. We're very happy to see you. We're thankful that you're here to see people indeed from all over the world.

Let me get back to some of these other questions that have been asked because there've just been so many of them. Here's one that says, what really makes a person high risk multiple myeloma? When we think of myeloma, we typically divide people into two categories. Do you have standard risk myeloma or do you have high risk myeloma? What we mean by that is that we've learned over the years that there's a form of myeloma that tends to be a little bit more aggressive. I describe it to my patients by saying it has more horsepower. It has that ability unfortunately, to just grow very rapidly, whereas most myelomas don't grow that rapidly and we can treat them, they stay in remission for a period of time. They will come back unfortunately, but typically not rapidly, and so that group of patients we want to identify because we may have to treat them a little bit differently, be a little bit more aggressive.

It's hard because even in our research world as we define high risk myeloma, so we want to do, let's say, clinical trials and high risk myeloma, it's not always easy to define it, but we've typically defined it through a staging system that's called the International Staging System that has been revised a few times, which is basically a combination of some simple blood tests, something called the albumin and the beta 2-microglobulin, as well as another test called the LDH or the lactate dehydrogenase, and then we add that to the genetic testing that we do on the cancer cells, on the plasma cells. These are not genes that a person carries per se, and passes onto their children. These are the genes that we look at of the actual cancer cells, the ones that are typically mutated or have changed in a way to make them cancerous and to keep them cancerous.

Cancer, in its essence is cells trying to be immortal, trying to live forever, and so often we see mutations and changes in them that can keep these cells alive for longer, and so there are certain genetic things that we've learned over time are connected to higher risk myeloma. The most common ones are when a part of chromosome 17 that we call the 17p arm, because remember chromosomes have a Q arm and a P arm, that's why we use that old expression, mind your P's and Q's, your own business, because everyone's chromosomes are different, and so if we're missing a part of that P arm of the 17th chromosome, it typically means we've lost or have mutated a very important gene there called the p53 gene, which is really helpful to keep things in proper rhythm in a cell, and so when that's deleted, then the patient can have high risk disease.

We also have what we call extra chromosomes. That can sometimes be a problem, especially chromosome one, the Q arm of chromosome one. When there are extra copies of chromosome one, that can be a challenge. And then we sometimes have what we call translocations. Again, I'm not making you all geneticists overnight by any means, but translocations just means a piece of one chromosome and a piece of another chromosome get merged together. We've talked about missing pieces of chromosomes, deletion 17p, adding chromosomes like chromosome 1q, but now sometimes we can have one piece of one chromosome matched up with another, and the most common one in the high risk group is what we call translocation 4;14, so it just means a portion of chromosome four and a portion of chromosome 14 that normally should live separately, one on four, one on 14, actually get merged together, and that merger causes a genetic disturbance that can, again confer if you will, immortality and a more aggressive nature to that cell, and so that becomes really important in helping define myeloma.

There are other cytogenetic abnormalities that I can get into. There's [inaudible 00:14:27]. There are several others that I won't go into a lot of detail, but those are really the primary ones. And then lastly, you've got those blood tests, you've got the genetic tests on the marrow, but then sometimes even just if you will pragmatically, when we see someone's disease relapsing very quickly, that can be considered more of a high risk feature, namely, for example, if someone has a bone marrow transplant and their disease grows back very quickly, that can be a problem where we know that unfortunately, that literally means the disease has become high risk, typically if the disease comes back within a year of their transplant. So even though at diagnosis we make that distinction between standard risk and high risk, there are patients unfortunately over time that can go from standard to high risk because some of these genetic abnormalities can be what we call acquired later, meaning that they can come into the system later. Thank you for that very good question. That was excellent. Here is, again, more questions which I think are great.

One says, will mass spectrometry be widely available in the near future? Can mass spectrometry replace a bone marrow biopsy? Well, let me say, this is another favorite question of mine, so thank you Leah for asking this question. I think you may get some swag sent your way because this was really... I think this is a very hot area of research and work right now. As I answer this question, let me just remind everybody who's live, I see many of you keep joining, which is great. Please drop in the chat box your name, where you're from, and some questions because we're still have a little bit more time to cover some of those questions.
What is this whole mass spectrometry business? Myeloma is a disease that originates in the bone marrow, where those plasma cells that we normally have to make our good antibodies become cancerous, and so by extension, unfortunately, these bad cells that live in the bone marrow that are now growing out of control, because we said, remember, cancer is immortality essentially, these cells grow, and now instead of making good antibodies that fight off infections like Covid and all these other terrible things that we face, now these bad antibodies, these antibodies are bad and they can actually damage us. Well, antibodies essentially are a form of a protein, and so we can measure proteins in the blood. That's why for all of you who know this, who've been patients and care partners to patients, when we look for myeloma originally, we do a bone marrow test and that's where we look for those bad cells because that's the headquarters of the myeloma. But thankfully, we don't do a bone marrow test every single month or every single time we want to evaluate the disease.

We do a blood test that looks for those proteins in the blood, and we primarily do that through what's called a serum protein electrophoresis. That's been old school test, but still works really well, that looks for the protein, and sometimes those proteins break off, big ones and small ones, or heavy ones and light ones, and so we secondly do what's called a serum free light chain test or measurement because we look for those little proteins or those little antibodies in the blood as well. Historically, as we follow patients with myeloma, we look at the serum protein electrophoresis and the light chain. Sometimes we look for it in the urine as well, because it can come up in the urine, and so we follow the activity of the disease based on that. The M spike or the monoclonal protein, which means it's the bad protein, the identical protein of the cancer, or the serum free light chain measure and the ratio that comes from the two different light chains that we have, one is called kappa, one is called Lambda, that becomes the measure of myeloma.

We can say to a patient, oh, your myeloma is shrinking because we're giving you the treatment and we're seeing the M spike go down or the light chain go down. Well, now this new technique of mass spectrometry has been developed, and we've actually had it around for a long time for different contexts, but now finally being used for myeloma, it's a very sophisticated technique that very meticulously looks at all proteins in the blood with even more precision than the serum protein electrophoresis and the serum free light chain test, and so a lot of research, because the theme today is research, a lot of research is going on right now looking for ways in which we can replace those older tests of the serum protein electrophoresis and free light chain measure with mass spectrometry because it can capture it more carefully.

Now we need a much more sophisticated tool. The mass spectrometer, the machine, is very initially costly, but it's very quick and very effective. There are certain places that are starting to use it now. Where I used to work at Mayo Clinic, they have introduced this as well to look for the bad protein of myeloma patients in their blood, and the test can be done very quickly once that machine is set up. An answer to your great question, Leah, we're not quite at the stage where it has crossed over to being mainline. This is being evaluated by the FDA, this is being looked at now, or it's being used very much so in research purposes, and we're using it, for example, in the big Iceland study that I mentioned, the iStopMM trial, but we do anticipate probably in the next year or so, that we're going to be able to be doing more mass spectrometry routinely in the clinic to measure patient's protein. Now the second half of your question, that's one of the reasons why it was such, I think, a great question was, is this going to replace a bone marrow test?

We would love to replace all bone marrow tests. Right now, we don't think it would immediately replace the initial bone marrow test that we need to make the diagnosis, but we are using mass spectrometry to detect changes that we might not otherwise see with more crude tools, where we can look very carefully, even tiny amounts of the protein that may be reemerging when someone relapses. We may be able to detect it earlier, because one of the things we've learned in research and now in clinical practice is, if you can catch a disease earlier, and the word we often use is intercept the disease earlier, patients are going to do better, which makes sense. I don't want to wait until the tumor, the myeloma grows to be a big thing to intervene, I want to be able to intervene early, and so mass spectrometry is one of those ways we may be able to do it.

While I'm on that subject, let me just say, there are some other ways in which we have also looked to detect one of the things that in the academic position I have at our lab, Dr. Jonathan Keats and his team there, it's such a privilege to work with him, are really doing some fascinating work to be able to detect even tiny, tiny amounts of myeloma by looking for very rare plasma cells that may themselves make it into the peripheral blood, which with time may reduce the need for doing bone marrow tests. I think any myeloma patient, frankly, any blood cancer patient thinking of the month that it is, even those with leukemia and lymphoma and other blood cancers, would love to get rid of bone marrow testing. Right now it's still important because that's how we can assess a bone marrow, but I hope, Leah, that with time we will be able to, if not eliminate, at least reduce the number of bone marrow tests that we have to do over the long term, so thank you for that excellent question.

Okay, there are some more questions and time is going quickly. We only have about five minutes left, so I will try and jump to another one. Here's one that is actually asking us about part of the IMF's clinical trial called the ASCENT trial. It says, I saw the IMF posts that 84% of patients in the IMFs ASCENT trial were MRD-negative, what does that mean? Well, that's a great question. I could talk about it all day, but in short, this was a study where we were looking at patients with what we call high risk smoldering myeloma. Patients with active myeloma, once unfortunately the myeloma has started to damage the body, we call it myeloma, but for a lot of people we can detect this little bit of the abnormal protein in the blood, but it just hasn't grown to a level that it's causing any damage.
There's two categories for that, something called MGUS or monoclonal gammopathy of undetermined significance, which is a mouthful, but it just basically means that you've got this little schmutz of protein but it's not hurting you. And then in the intermediate area, there's something called smoldering myeloma where when we do the bone marrow test, it is more than 10% plasma cells, but it is not at a level yet that it's damaging the body or about to damage the body. We don't know really what to do with those patients. Should we treat them, should we treat them mildly, should we treat them more aggressively? The ASCENT trial was trying to answer this question by saying, what if we were quite aggressive with patients and giving them a very intense regimen with daratumumab and carfilzomib and lenalidomide and dexamethasone, some of you know these words, some of them it's new to you, but it's basically using what we call a quadruplet or four drugs together to try and see if we can really squish down this disease.

As we measure myeloma, as I mentioned, we look for that bad protein in the blood, we have those tests of the serum protein electrophoresis, the serum free light chain measurement, and now starting to use mass spectrometry, but sometimes those go down to basically where we don't measure the disease anymore, so we want to check in the headquarters of the disease in the bone marrow, and that's typically where we're doing what we call MRD or minimal residual disease testing. Now, in the future, I'd love us to be able to do MRD testing in the blood, and we're working on it, and mass spectrometry may be a part of it as well as flow cytometry and deep sequencing, the other methods that we do this, but the concept of MRD is saying, not only can I not measure your disease in your blood, but when I look into the bone marrow, I can't find any of the disease.

We look for one myeloma cell, a mix, 10 million or a hundred million cells, and sometimes even more depending on the technique that we use, so it doesn't mean cure, but it means that patient's disease is way, way down, and we've learned that if we can get that disease way, way down, it often stays down for a very long time, especially if we measure it twice and it's still down, what we call sustained MRD or minimal residual disease. This ASCENT study was, it's still early on, it's not final, but it's very exciting to know that with this strategy, catching patients a little bit early before their myeloma becomes very active, we can get the overwhelming majority of them into MRD-negativity.

Well, it's hard to believe that our time is almost gone, but I want to, before we close off the half hour, first of all, let me thank you again for joining me, Dr. Joseph Mikhael as the Chief Medical Officer of the International Myeloma Foundation, for this Facebook Live as we kick off Blood Cancer Awareness Month.
You'll be seeing lots of posts over the next week and over the whole of the month regarding myeloma. We want you to know myeloma, knowmyeloma. Go to knowmyeloma.org to learn more about it. I want to be a preview, in fact, I'm going to tell you, I'm pretty much just the appetizer. The main dish is yet to come. We have three amazing Facebook Lives coming on September the 12th. You'll get to hear from Beth Famine, who is one of the most incredible nurse practitioners I've ever met in my career, and she's going to be talking about the education side of blood cancer awareness and multiple myeloma. And then on the 19th of September, Ilana Kenville, who is from the IMF and she works with us in our fundraising department, she's going to be talking about how we can fundraise for the cure, and she always has a disturbing amount of energy, so she's going to be great, you'll not want to miss Ilana's presentation.

And then on the 26th, Danielle Doheny is going to be talking to us about advocacy, health policy and how that is an important venue for us to look towards a cure and to promote the principles that we want across our country so that our patients can be treated the best. This is a challenging time in our world and in our country about drug access and ensuring that everyone can get the right treatment. She's so deeply committed to this, and this disease is very personal to her. She's wonderful, and so you're going to enjoy those Facebook Lives that each time, just like today, they're going to be at 07:00 PM Eastern, 4:00 PM Pacific on the 12th with Beth Faiman, on the 19th with Ilana Kenville, and on the 26th with Danielle Doheny, so please don't miss that opportunity to do so.

I also just want to take a quick moment to say that we can't do a big campaign like this without a lot of support and help, so for all of the IMF staff, for all of the patients, their care partners, we really appreciate your help and support, and indeed, we've had a lot of corporate support for this particular activity, and I want to particularly say thanks to Bristol Myers Squibb, to Janssen Pharmaceutical Companies of Johnson and Johnson, Karyopharm Therapeutics, Pfizer, Sanofi, GSK and the Binding Site for their support for Blood Cancer Awareness Month. Hopefully, today you've learned a little bit more about myeloma. Hopefully, I've excited you a little bit about what's going on in research.

As I close off my last minute, let me tell you that in 25 years of doing myeloma, I've never seen as exciting a year of research as this very year. We've just had three drugs approved over the last few months. We're developing new CAR T-cell therapy where I can take T-cells out of a patient, train them to attack their myeloma and give them back to the patient.

Secondly, we're doing tremendous work in what we call bispecific antibodies where we give a drug that has two arms, one arm grabs onto the myeloma, the other grabs onto a local T cell or other cell and engages it to destroy it. I mean, this really almost sounds like a futuristic movie, let alone the reality of what we're doing. Amazing research is going on across the whole of the world in myeloma, and the IMF has the privilege of spearheading and collaborating and coordinating so much of this research, and so we're delighted to do so.

Enjoy your evening, enjoy your Labor Day weekend. Thank you so much for joining us. Make sure that you learn more about myeloma at knowmyeloma.org, and we really appreciate your attention tonight. Thank you so much for joining us.