Full Show: Studying MGUS and Smoldering Myeloma Genetics and Using Immunotherapies in High-Risk Smoldering Myeloma with Dr. Elisabet Manasanch, MD Anderson Cancer Center

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Elisabet Manasanch, MD
MD Anderson Cancer Center
Interview Date: April 26, 2017

Summary
MGUS and smoldering myeloma are precursor conditions to multiple myeloma. For those with the early markers, who will progress and who will not? Dr. Elisbet Manasanch at MD Anderson Cancer Center is using myeloma genetics testing to help determine answers to this important question. Dr. Manasanch describes a study she has open to test MGUS and smoldering myeloma patients using a test called the GEP-70, a gene expression profile test and observe the way that their disease potentially changes over time. The answers to this study will help myeloma specialists know how to segment patients into different groups and identify who may benefit from early treatment. She also describes a study open at MD Anderson for high-risk smoldering myeloma patients using a monoclonal antibody called Isatuximab. 

To find the two clinical trials discussed in this show, click here:

Isatuximab Clinical Trial for High-Risk Smoldering Myeloma

 

MGUS and Smoldering Myeloma Genomics Study

To find all clinical trials at MD Anderson Cancer Center, click here:

MD Anderson Myeloma Clinical Trials

Dr. Elisabet Manasanch on Myeloma Crowd Radio

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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. Now, before we get started with our show today, I just want to let you know that we’re almost at the end of our Muscles for Myeloma Program which concludes on April 30th. Today, we’d like to give a shout out to Dean Preston, who will be weighing our prize for completing all the Muscles for Myeloma challenges. And UAMS is the leading facility for this year’s program and we thank you for participating. We hope you have learned more about why fitness is important for myeloma patients. If we’re fit, more treatment options will be available to us, giving us longer life and better outcomes.

Our show today is primarily for patients with early conditions that may or may not become multiple myeloma. Today, we’ll be talking about how researchers could potentially find MGUS and smoldering myeloma patients who are likely to progress to myeloma using myeloma genetic testing and other lab or imaging values. There is no doubt that this work will be equally important for myeloma patients as new discoveries are found. So today, Dr. Elisabet Manasanch of the MD Anderson Cancer Center joins us to discuss the study of myeloma genetics as well as the clinical trial she is running for high risk smoldering patients. Welcome, doctor.

Dr. Manasanch: Hello. How are you doing, Jenny?

Jenny: Doing great. We’re so happy that you joined us and we were talking before the show started that this is our 99th show. And I was so hoping it would be our 100th show because we started this series with Dr. Orlowski from MD Anderson. You and your facility have just some tremendous work going on and some of the largest numbers of clinical trials in the nation. So, we’re excited to have you on today and hear a little bit more.

Dr. Manasanch: Yes. I’m very excited to be able to talk about this. We have been working on this for the last three years. We’ve been really, really working very hard.

Jenny: Let me introduce you before we get started, I didn’t do that yet, and then we’ll go right to our questions, and you can explain what it is for these two studies because they’re fascinating.

Dr. Manasanch is an Assistant Professor of the Department of Lymphoma and Myeloma at the University of Texas, MD Anderson Cancer Center. She graduated with an MD degree from the University of Barcelona in 2005 and received her MHSc in Clinical Research from Duke University in 2014. She pursued Internal Medicine and Medical Oncology Training at the University of Massachusetts and National Institutes of Health and is board certified in both specialties.

During her fellowship training at the NIH, Dr. Manasanch focused on the research and treatment of plasma cell dyscrasias. In 2014, she was awarded the MD Anderson Cancer Clinical Innovator Award to study predictors of outcome after anti-CDA antibody therapy in intermediate and high risk smoldering multiple myeloma. She received the IMF 2015 Brian D. Novis Research Award to implement minimal residual disease testing in multiple myeloma. In 2016, she received the High Impact Clinical Research Support Program Award to support clinical research personnel funding.

Currently, she leads the Myeloma Precursor Disease Program at MD Anderson with a focus in understanding early stages through new technology and applying immunotherapy to early treatment. A perspective observational clinical trial in MGUS and smoldering myeloma is currently happening, and she will describe that and many interventional trials with monoclonal antibodies in intermediate and high risk smoldering myeloma are ongoing and she will talk about that as well today.

So before we get started, Dr. Manasanch, maybe we can back up because I know that MD Anderson has this Moon Shot program and part of the Moon Shot program is for high risk smoldering myeloma patients. Do you want to describe what that program is and why you decided to include high risk smoldering myeloma?

Dr. Manasanch: Well, so it’s very interesting that you’re mentioning the Moon Shot that we have here at MD Anderson because actually these two studies that we are going to be talking about, they are actually part of what we call the Flagship 1 program of the Moonshot. So, part of this research that we’re doing in MGUS and also in high risk smoldering myeloma is funded through the MD Anderson Moon Shot program. And so, the reason we wanted to do high risk smoldering multiple myeloma and include these in our Moon Shot for high risk myeloma is that these patients that have high risk smoldering myeloma, usually the perceived risk is about 75% risk of progression and depending on the series, it’s 75% risk of two or five years following the diagnosis of smoldering myeloma.

These patients really have a substantial risk of morbidity and mortality. We’ve seen just a few years of diagnosis, and we felt that we really should be doing therapy, especially now that we have so many new therapies with all the new antibodies to target these patients to try to see if we could allow them not to have this progression to symptomatic myeloma or if we could cure them if there are less genetic abnormalities beforehand. Right now, we’re in the very early stages of this where we’re doing single agent antibody treatment. However, in the future, we could do combinations with this, and that’s where things are probably going to get a little bit more interesting.

Jenny: Yes, because then you have to decide, and this is where your study comes in, who is likely to progress and who isn’t. When you add combination therapies and you’re starting to talk about more toxicities and things like that. Who is it worthwhile for and who won’t benefit?

Dr. Manasanch: Well, this is what we are trying to look into for our study for the first prospective observational study that includes 100 patients with monoclonal gammopathy with known significance and about 100 patients with smoldering multiple myeloma patients and this is any risk MGUS and any risk smoldering myeloma patients. We have currently accrued about 25% of the patients in about one year. We have a very good accrual rate. The features that we’re looking for for these patients to see if they are going to progress or not is, of course, we look at the immunoglobulin levels, we look at the level of the monoclonal protein, we look at the level of the light chains in the blood and the light chain ratio and mostly the involved divided by the uninvolved ratio. If patient has an immunoglobulin G kappa of the smoldering myeloma or the MGUS is making, then we would look at the kappa divided by the lambda. And if they had a lambda, we would look at the lambda divided by the kappa. These are all the regular tests that doctors do all the time. There are some features that we look at to predict progression. However, these features, they vary depending on who you talk to. There are different risk models and depending who you ask, depending on the country where they do the studies, depending on the institution where the studies are done.

This study with 200 patients, what we’re going to try to do is to study more in depth the immune system for one and then also the genetics. We have a lot of correlative studies not just looking at sequencing of a DNA but we’re also be doing RNA sequencing like gene expression. We’re looking at a lot of these things, not only of the myeloma cells but also the cells that are around the myeloma cells as well as the immune cells both in the blood and the bone marrow. I think that hopefully the study that we’re doing, what it’s going to allow us to do is to have one model that is more accurate of what we have right now. When patients come to the clinic, we can predict in a more accurate way and that this model can be replicated in other centers. That would the ideal information that we would derive from this. Again, we’re accruing quite quickly.

I think we can probably have some preliminary results for this within the next year, year and a half. We’re going to be presenting this. We’ll present some data probably later at ASH this year with all the clinical data that we have for the patients we have, and then we are probably going to try to present also some of the correlative data probably next year.

Jenny: This is fascinating because you’re setting the markers that you get back, your M protein and the light chains, and those are just blood and bone marrow tests. And then you said you’re also studying some genetics testing. I’m going to ask you some follow-up questions about that. But you are also studying the immune system. So how do you go about studying the immune system? Because people say that, well, everyone may be exposed to cancerous cells and then our immune system just kind of tackles it down and we never developed cancer. But obviously, in myeloma, the immune system is too weak to kill all the myeloma cells by itself, and so it kind of gets out of control. So how do you better study the immune system?

Dr. Manasanch: What we’re doing with these studies is we have very good collaborators. One of them is Dr. Sattva Neelapu, who is an immunologist, and he has his own laboratory here at MD Anderson. What we do is we have him analyze samples of peripheral blood. So before and after treatment in the case one of the patients have high risk smoldering myeloma in the treatment on studies or in the other patients and the ones that are in the observational study at certain time points which is usually about every six months. What he does is he sorts the cells from the blood and takes out all the white cells and analyzes them and looks at markers that are in these cells.

There are many, many different types of white cells. He looks at all these different types, and then he looks at markers on the cell surface of these cells through a technique called flow cytometry and looks to see if there are inhibitory or activation markers that could help us understand why some people progress. For example, if you have some inhibitory markers in your myeloma cells, let’s say in the blood because we do have patients who have precursor disease, if you do flow cytometry, which is a very good technique to sort cells in fluid, usually we’ll find these abnormal cells in the blood.

So, you can study these cells and let’s say these cells have these inhibitory markers, so when the immune system cell, another immune system cell, let’s say a T-cell or an NK-cell, these are different types of cells that can recognize these abnormal plasma cell or myeloma cell and kill it, when they kind of attach to it, then the myeloma cell has this inhibitory marker and doesn’t allow these other immune cells to kill it. If you have a lot of inhibitory markers in the myeloma cell, then that’s a sign that maybe you could progress because your immune system is not ready to fight it. One treatment for that, it turns out that patients are progressed who have things like this would be to create an antibody that is going to actually bind to this inhibitory marker on the myeloma cell and is not going to allow this cell to have this as protection and then the immune system will attack it.  This is one of the things the way that you can study.

There are other ways that you can study the immune system. Flow cytometry is one, and you can do this in the blood and in the bone marrow. And then you can do something called NanoString, which is what we are going to be doing in these studies as well, which is going to be looking at gene expression of different genes that are involved in the immune system. You can also look at that. Usually, it’s mostly in the bone marrow. That’s another way that you can do it. You can also do stain. You have a bone marrow, and this is something we are looking at for our smoldering patients is looking at — once we’d take a core biopsy, they are looking at this core biopsy and doing stains.

There are many new technologies right now where you can actually take a core biopsy in the same slide, and you can stain it with an immune marker. Let’s say a molecule like, for example, we could stain it with CD38 because we know that there are antibodies are against it, or you can stain it with PD1 or PDL-1 which are markers on the immune cells at the myeloma cell, and you could do one stain and then you can delete it. They have a way to delete that stain and then on the same surface, on the same slide do another stain, and then you can look at the architecture of the immune system in the bone marrow. This is something that has not been done before to my knowledge. This is something that we are looking at.

There are many, many ways that we can look at the immune system to find this out, and I do think that we will know a lot more in the next probably a couple of years. If there are any of these markers that are important in the progression, I think that we have probably the means to find them. It’s very interesting. I can’t wait to have some of these results.

Jenny: Yes, so exciting. Earlier you talked about the typical markers, the myeloma markers that we get. Now, you just talked about the setting the immune system. You also talked about the bone marrow marker environment. Are these inhibitors that you are talking about what you are looking for in the bone marrow microenvironment, or are there other features that you are also looking at for that environment?

Dr. Manasanch: Well, the other immune cells, they are part of the microenvironment, so all the T-cells, the NK-cells and macrophages. All those are part of the immune system and are part of the microenvironment. Right now, what we’re going to be looking at these markers in these cells, mostly in the immune cells and then markers in the myeloma cells. But we also have, for example, when a patient comes in and they decide to participate in one of the studies, the sample of bone marrow that we take that is, in this case, an aspireate, so it’s the liquid part of the bone marrow. We separate this into the microenvironment part and the tumor part. We have both samples stored. You can do the same test for both parts. You can do it in the myeloma cells and the environmental cells. But again, for the microenvironment where we’re looking at the most right now is the immune system in that microenvironment because it has not been described a lot especially in smoldering myeloma and MGUS.

Jenny: Right. Yeah, that’s terrific. And then when you talk about the genetics, it sounded like some of this is the NanoString is the gene expression profiling. So is that part of the microenvironment? Are you doing that on the actual myeloma cells? Like you just said, you can do it on both.

Dr. Manasanch: We can probably do it in both because we have both samples. From the get-go, we do gene expression, as you know, with the first study that we have, we’re collaborating with Signal Genetics or now Quest, and I know there is a question about whether this is the same as the GEP-70 and it is, it’s that same test. All the patients have that test done, and what it analyzes is the gene expression of the tumor cells. The GEP-70 looks at the tumor cells, but we also have microenvironment cells. We can actually perform a different test which is a NanoString but it’s similar to the gene expression. We can look at that in the environmental cells and also you can do RNA sequencing which is also looking at the expression of the genes. We also are doing that in the microenvironment cells, so the ones that are not the tumor cells and also, of course, in the tumor cells.

We are doing all these. We can do it in both parts but the GEP70 that now Quest has, that one, those results, they only look at the tumor cells. But you could have as a signature from the environment. You could have like, for example, an immune signature. Again, Dr. Davies and Dr. Neelapu have actually worked on this for lymphomas where they do immune signatures. You can see depending on how the immune system looks your response to immune therapy.

Jenny: Oh, that’s so fascinating.

Dr. Manasanch: So that’s where we’re going. Yeah, it’s amazing. I mean it’s really amazing. I have to say, science right now and we have so many technologies right now to do all these things. It’s really, really exciting.

Jenny: In RNA sequencing, how does that differ from that gene expression profile or that GEP70 test? What are you looking at that’s different from that test?

Dr. Manasanch: Theoretically, we’re doing RNA sequencing. As you know, we all have DNA and then the DNA is sort of stored inside the cell. We are really not using it that much. It’s just when we need some expression of some proteins, then there is a whole machinery in the cell that goes into the nucleus and takes out this DNA. But the way this DNA information gets to the rest of the cell is through RNA and then translation into protein. When you are looking at the RNA level, you are looking at what is being expressed in the cell, not necessarily abnormalities in the sequencing but what is being expressed at a later level. It’s a little bit later on in the transcriptional level.

I think the main difference with the gene expression that we have right now is they both look at RNA levels but I think that with RNA sequencing, maybe this is a little bit more accurate ( or gives more information) because you actually do all the sequencing which in gene expression you use only known transcript-specific probes but unknown changes may not be detected, so you don’t necessarily do that (sequencing versus using known probes). It’s good to have both. It’s possible that the genetic expression is going to be similar, but we don’t know that so it’s good to have both so you can compare.

Jenny: All three of those are three totally separate ways of testing to get a whole complete picture of a patient. That’s really amazing. Oh, actually four ways if you include the blood. How about imaging tests as well?

Dr. Manasanch: Imaging test, as you know, I think that the best test that we have for myeloma, I don’t know if you will agree with me, I know you are very experienced, but the best test that we have to look at imaging of myeloma are the whole body PET-CT is one which is excellent and also it can give you information on how active some of the lesions are. That’s very useful visually. It’s very easy to see. And then you can follow that with time, right? And then another one which is not available everywhere is a whole body MRI, which allows you to see different infiltrate in the bone marrow depending on how many – if you have a lot of infiltrate, it looks in a different way than if you don’t, if they have a lot of myeloma. Those are both very good tests.

Ideally, for this study, a patient should have at least a recent PET-CT or whole body MRI to make sure you don’t have any of those lesions, and you truly can go on one of these smoldering studies either for treatment or for follow-up. In our studies, what we do is we usually recommend that a patient has a PET-CT whole body because that’s our test that we have here a standard at least a month before they enroll in the study. Some of the patients, they had a PET-CT three months before and the insurance, they don’t cover it. Sometimes they don’t want to cover it at all, which I think is a problem in our field. But when they do cover it, they don’t want to cover it every couple of months or every three months. If the patient has had a PET-CT two or three months prior, we usually just do a skeletal like the X-ray. But the best tests are the PET-CT and the MRI to look at the bone marrow and to look at the lesions. Usually, patients have to do at least a PET-CT.

Jenny: Okay, great. You start with the PET-CT and then what do you do for the study for the patients? You said you’re testing them every six months?

Dr. Manasanch: Yes. For this prospective study, so these patients, usually what we do is when the patients enter the study, there is usually a need for an evaluation. If we think that the patient, you know, there has been a long time they haven’t done any testing, then we usually order a bone marrow to look at the infiltration of the core biopsy. As you know, they changed the criteria for myeloma. Now, if you have 60% or more plasma cells, you have myeloma that needs treatment. What’s important I think every now and then to follow a bone marrow in patients with smoldering myeloma to see if they are meeting these criteria.

They do a bone marrow biopsy. We do some imaging. We do blood work and a 24-hour urine. And then if those results show that there is no active myeloma, then they can participate in the study. If they have very high risk smoldering myeloma, they can do a treatment study. And if not, we offer to do this observational study. In the observational study, we follow for every six months for three years. As you know, some smoldering patients, you need to follow them every three months. We don’t take research samples every three months. We only take research samples, which is only blood at that time once every six months. We take a research sample of bone marrow whenever they start the study. And then after three years, we usually repeat the testing to make sure there is no progression, and we take another sample of bone marrow, and we take another sample of blood. And then after three years, the study finishes.

However, I have to say that many of the patients that we have on these studies, they are our patient is in the clinic. They’re not going to stop seeing us because, as you know, the risk of progression if you have MGUS or smoldering is something that kind of lives with you, so it’s something you have to follow for life. We will probably have long-term data for these patients and probably when the study finishes, we will allow to have a follow-up cohort of patients that we can call and ask how they’re doing. Or if they come to our clinic, then we’ll follow them and we’ll follow to see if they progressed or not. It’s going to be very interesting to see the data five years from now, five years of followup, 10 years of follow up and so on.

Jenny: Absolutely, that will be really valuable. Your overarching goal is what you said at the beginning in the show, which I kind of what I want to stress, is to see, can you treat patients at an earlier stage and avoid heavy treatment in the future? Could you cure it early? Is that really what you’re going after?

Dr. Manasanch: Yes, we are. And of course, you always have to start slow. You don’t start a study with new medications, some of them not even approved in multiple myeloma. We’re doing combinations. Right now, we really are trying to focus on immunotherapy. We’re trying to build immunotherapy treatment for this population which is a little bit earlier than myeloma. Why? Because it has many advantages. I mean if you think about it, immunotherapies can be toxic. I mean I’m not saying that they don’t have any side effects. They can have side effects. But if you compare it with the treatment with dexamethasone and doing like lenalidomide or doing like a bortezomib or doing a transplant, all those treatments, they seem sort of a little bit aggressive, right? And how do you decide we do that?

We are trying to do something that seems a little bit less aggressive but that could be very effective. What we’re trying to do is build an immunotherapy treatment for early precursor disease in multiple myeloma. We are starting by testing out single antibodies, so one antibody at a time, and we are looking at these results. If these results look promising, then we can combine this with other medications. Some of the advantages, as you know, there are studies where we do lenalidomide for smoldering myeloma. There is a Phase 3 study ongoing right now, and there are many other studies with antibodies and with lenalidomide and other medications. But some of these medications, sometimes they say they can damage the stem cells. You maybe want to do a transplant, then you have to collect stem cells, right?

Within immunotherapy, you probably don’t have to do that. There is really no evidence at these antibodies damage the stem cells. That’s one of the advantages. The other advantage is that the immune system might be a little bit better early on than when you present for the first time and you are hypercalcemic and have tons of lytic lesions and you need to go into the hospital for treatment.

It has potentially many advantages. I do think it’s still very early on, but I think that there is a future in this field of immunotherapy in early myeloma. Of course, there is also this potential for relapsed myeloma and for early myeloma, I mean there are studies right now with antibodies frontline, antibodies to the standard treatment for newly diagnosed myeloma. There are many studies with antibodies in relapsed myeloma. But I think that particularly in this area that is early on, it’s very interesting and I think it’s very promising. Not everybody is doing this right now, so we are one of the centers that is mostly exclusively doing this, that is trying to build an immunotherapy platform in precursor disease.

Jenny: I think all of the patients really appreciate what you’re doing. Let’s talk about how to join the study because obviously if you’re an MD Anderson MGUS or smoldering myeloma patient, this is just an observational study. Since you’re not doing any treatment and it’s observational, to me, these are the kind of studies that are just no-brainer studies because you’re there anyway. You might be taking a few more samples, but it doesn’t matter. I mean you are learning so much about what can happen. But can patients that are not MD Anderson patients typically come and see you, if they’re in kind of your geographic area?. They could come and give you a sample every six months, and that’s not a huge deal.

Dr. Manasanch: Right. A lot of the patients decide to do that.  As you know, we’re a big center. We have a lot of patients coming to us from other states. We have a lot of patients coming from Florida. They’re coming from parts of the state of Texas. Most of the patients, they don’t mind. Now, if there is a patient that would like to participate in the study and is in another state, then they would have to come here. Unfortunately, this study is an investigator initiated study that we’re only really doing here because the way sort the cells and we analyze the samples, we really have all the labs here, so it will be difficult to have somebody ship the samples. They have to be collected in a certain way, et cetera.

Unfortunately, they’re only available here and so they would really have to come here and be here every six months for three years. So that’s the only downside, if you’re in New York, you cannot do it in New York. However, the smoldering treatment study is a multi-institutional study, multi-standard study, and we are the leader, MD Anderson. However, we are working with Dr. Ola Landgren at Sloan Kettering and also Dr. Sundar Jagannath at Mount Sinai. We are now working on getting this study that is with an antibody in smoldering myeloma open in New York so the New York patients will be able to do this study in New York. But the observational is only here.

Jenny: Okay, that makes sense. Let me ask you a few more questions about the observational study before we move on because I want to make sure we have enough time to cover that study, the second study. Are there any clues that you have learned so far about MGUS and smoldering myeloma or some hypotheses that you’re going into this observational study with, just things you kind of want to dive into a little more I guess or you are just starting from scratch and you kind of want to just get a picture of everything?

Dr. Manasanch: So together with Dr. Neelapu here, what we did is we have not yet looked at the samples coming from the prospective study, which are kind of precious samples. We have not looked at some of those results. Again, most of these studies, both the genomic stuff and the immune stuff, their samples are stored and we are going to test for this in the next few months. What we did is we have a myeloma tissue bank here and so we took some samples from smoldering patients that had progressed and compared them to smoldering patients that had not progressed from stored samples in our tissue bank.

What we saw is that there were some of these molecules that we’re activating inhibitory markers that had abnormal levels compared to normal controls. We think that there is going to be something there, and we have to really validate this in our prospective series. But really, that’s what we are looking at right now. I also think that the genes are going to play a key part in this. We know this for a while. This is why the staging system in multiple myeloma has the genetics as part of the staging system. If you have something that is perceived as bad genetics, then you’re stage three, right? That’s the new staging system for myeloma.

Also, they are going to play a key part in precursor disease. The biology of the MGUS or the smoldering myeloma that you have is going to play a key part. And so how does that play together with the immune system? If you have a very bad type of smoldering myeloma or MGUS, if you have a very strong immune system, then what happens? Or if you have bad myeloma cell genetics and you have a weak system, what happens? So that has not really been studied a lot. I think that a lot of these things that we’re looking at are very new, but I think that we will also probably corroborate and validate many of the things that have already been said such as that. Having suppressed immunoglobulin is probably not a good thing if you’re looking at progression to myeloma, having abnormalities of chromosome one which has been seen in many studies to be a sign of progression to myeloma and also to be for higher risk for myeloma is also probably not going to be a good thing, having high expression of the genes that are associated with bad myeloma when you’re diagnosed with active myeloma or having high levels of expression of these genes that give kind of immortality to the cells that have been already identified, for example, by the Arkansas group. I think we’re going to see a lot of these things that are going to be tools for our patients that we’re hoping to look at this from the point of view also of the immune system.

Jenny: That has a really fascinating perspective to it. I think it’s really amazing and I love that you’re doing that. One more question I guess. What’s your opinion about larger MGUS screening? Let’s say you do start learning a lot more about who will progress and who won’t and at different stages and you can kind of predict it. I guess that takes some of the fear out of screening everyone for MGUS and then have people not know where they stand.

Dr. Manasanch: I think that it’s a very good idea to screen, to do a study or to screen for MGUS. And the reason for this is that most people don’t know, right? Most people, if they have myeloma, they — I mean not everybody goes to the primary care doctor once a year; that’s true. And if they do, not all the myelomas have high protein in the blood. That’s a typical thing. You go to your primary care doctor and they see a high total protein and then they send you to an oncologist and then they find out you have a bad protein in the blood and then there is a workup on its myeloma.

The myelomas that have light chain myeloma which is 15% or 20% of all the myelomas, they aren’t necessarily associated with the height of the protein in the blood. The primary care doctor is not going to see it. You have to do the light chain test in the blood, and they don’t do that. First of all, great idea. The study that Dr. Sigurdur Kristinsson is doing in Iceland, I think it’s a fantastic idea, my full support. It’s a very ambitious program, but I heard that they are accruing very well. It can answer many potential questions.

The main question is do we have to screen everybody for MGUS? I don’t know the answer to that yet. Why? Because I don’t know what the study is going to show. I do know however that many studies, mostly retrospective studies looking at patients that had a prior diagnosis of MGUS or not, patient with active myeloma with a prior diagnosis of MGUS or not, those that had the prior diagnosis of MGUS were followed had a better overall survival in a few studies. It’s not just one study. It seems that knowing that you have something that could develop into myeloma and being followed for it might make a difference. It could also be the biology. If you have MGUS for 20 years and then develop myeloma, chances are your myeloma is better risk than somebody who nobody sees anything and then all of a sudden you have a horrendous myeloma. The biology of the myeloma is different.

I think that it’s a great idea to do the study. Now, we have to see the results. I think that the rate they’re accruing patients and how they are doing everything in Iceland, we’ll probably know in the next few years. What they are doing is they are doing these three arms in the study and there are some patients, they don’t do anything. They don’t tell them they have MGUS because that’s the standard. People wouldn’t even check. Then another arm, they follow them in the clinic but they don’t do a bone marrow or imaging or anything. And then they have another arm where they do with a bone marrow and the imaging and they try to stage them a little bit more and take samples to do sequencing of the DNA, of germ line DNA to see if there is any association with the germ line DNA, not the myeloma DNA, for progression and for risk of myeloma.

I really think we have to wait for that study to see. I think that it will be helpful if somebody else could do a similar study, maybe not similar because it’s very difficult to do these very large studies like hundreds of thousands of patients but something in this regard to compare and to validate the results that they are going to show. But I think it’s a fantastic idea. We really need to do this MGUS screening study to know what to do because I mean if we have some studies showing that if you know before, you do better, then why not, right? So that’s the basis.

Jenny: Right, yeah, absolutely. This might be an odd question or maybe even a dumb question, but are minimal residual disease tests ever used in MGUS?

Dr. Manasanch: You could use it, right? For example, how could you use it? I mean you could use it mostly in research. When I was a fellow at the National Institutes of Health and we were studying also MGUS and smoldering and all these, the flow cytometries that do MRD because MRD, I’m assuming you’re doing MRD by flow cytometry, not sequencing.  Or both. For sequencing, I don’t think so because you are not treating it, right? For flow, it depends, right? They say that minimal residual disease, you are minimal residual disease negative after treatment for active myeloma if you analyze two million cells in a bone marrow aspirate and you have less than ten or ten to 20 cells that are abnormal. That’s considered negative. If you take an MGUS patient and you analyze two million cells and they have 15 that are abnormal of the two million, you could say that it’s the same test. You wouldn’t call it minimal residual disease because you are not treating the patient, so it’s not minimal residual disease positive after treatment. And if you look at MGUS patients, in fact, MGUS patients usually will have a little bit more than minimal.

If you took the same test and you analyze two or three million cells, which is a lot by flow cytometry, in a diagnosed patient with myeloma, sometimes they test 200,000 or 500,000 cells, and almost all of them are multiple myeloma, many of them are multiple myeloma because they have so many in the bone marrow. But if you take somebody with MGUS and you do flow cytometry, you pick up those abnormal cells that’s going to be less than in newly diagnosed patients. But I think that it’s possible that there’s a little bit more than after a treatment for myeloma. But you wouldn’t call it MRD. You would say, we have done sequencing. You can sequence at VDJ segments so the immunoglobulin part of the M protein and then you can say this is what we are detecting in our diagnosis and this is the level that you have.  And you can follow this. I think that if you do the sequencing of this segment of immunoglobulin and you did this every year, for example, and a patient was progressing, you would see the levels of this go up. You would see more segments of DNA having this.

And if you do flow cytometry and this is actually one of the risk factors by some of the disease for progression is if most of the plasma cells that you have in the model are abnormal, they’re not good plasma cells, then that’s a criterion for progression. You could probably correlate this, and some people are looking at doing the liquid biopsies, which is taking peripheral blood, taking blood and looking at the myeloma cells in the blood and looking at the DNA in the cells in the blood from the myeloma and then saying what is your risk of progression? So that’s something that needs to be looked at for risk for progression. But you wouldn’t say MRD. You would say its flow or sequencing.

Jenny: You could call it something else.

Dr. Manasanch: Yes. And it’s possible that you could do a study where you could analyze this and then depending on the level, you could say maybe your risk is this of progression or these are the risks. Maybe there would be a correlation, you know?

Jenny: Yes. I’m just wondering if more sensitive tests would give you any more information. That’s all.

Dr. Manasanch: It gives more information. I mean what people look at is how many in by flow cytometry with MRD. It’s called MRD if you analyze a certain number of cells. If you analyze less cells, it’s not called MRD. It’s the same technique.

Jenny: Yes. Well, let’s make sure that we talk about your trial with this monoclonal antibody, isatuximab. Why don’t you just describe what it is and how that drug works?

Dr. Manasanch: Isatuximab is monoclonal antibody. It’s humanized, which means that the portions of the antibody have sequences that are human because many of the original antibodies were mouse or mice antibodies. It has many modes of actions to kill tumor cells, mostly to direct tumor targeting and also immune cell engagement. The way this drug works, so isatuximab which is a CD38 antibody mostly, it works through something that is called antibody-dependent cell-mediated cytotoxicity.

What that does is if you have a myeloma cell and myeloma cells almost universally express CD38, it’s a marker of the plasma cells. And what happens when you do this is you have I guess this protein, the CD38. sitting on the surface of the myeloma cell and then isatuximab is an antibody that attaches to this protein. What this antibody does is it sends a signal to the other cells in the immune system and says, hey, there is something here that is not right. It sends a signal to the immune system and the immune system, there have been some studies showing that the natural killer cells are the most important cells for this antibody to act so you can have then a natural killer cell that gets excited to see this antibody then goes and attaches to the myeloma cell and kills the myeloma cell.

It works through activating other parts of the immune system to target this cell that has the CD38. Theoretically, you have other cells that have the CD38 non-myeloma cells. Your immune system could also destroy it. But so far, the testings that have been done with this drug showed that it’s not very myelosuppressive. The other cells in the bone marrow, most of them, they don’t have a lot of CD38 in this direction toward if you have a lot of CD38. That’s one of the mechanisms of action is an antibody. It’s a protein. It’s not the hardcore chemotherapy that we talk about, for example, for people who have breast cancer. It’s not that type of stuff. It’s not high dose cyclophosphamide. It’s an antibody.

The main side effects of antibody drugs are infusion reactions because you are taking a protein that is foreign to your body and your immune system can have a reaction, like an allergic reaction. There is already an antibody that is approved for multiple myeloma and that we give in myeloma as early as after one line of therapy and that’s daratumumab. I think that they are very similar. With us giving isatuximab here we have not seen more infusion reaction. I think that if you give pre-medications, which is usually a little bit of steroid and then some medications to open up the airways and anti-allergy medications, most people do very well and they don’t get allergic reactions and the infusion is a few hours. It can vary from two to three hours to five, six hours depending on how quick the infusion is and that depends on how well the patient is doing.  But I think that it’s similar. I don’t see that there is a lot more infusion reactions with this medication with isatuximab than giving daratumumab for myeloma patients.

Jenny: How do the two drugs compare? Because I know when you have the same type of drug and the same drug class like even, let’s say, a proteasome inhibitor or something, those drugs can be radically different in the way that they work. Are these more similar in a way that they work and are just from two different providers, or are they structurally different in how they work?

Dr. Manasanch: I think they are very similar, definitely from the side effect point of view. So far, it looks very similar. From a mechanism of action, it’s also similar. Some people advocate isatuximab, that the antibody-dependent cytotoxicity might be a little bit better. But the truth is to know for sure which one is better, there would have to be a study comparing isatuximab to daratumumab, and I don’t think anybody wants to do that study. I don’t think it’s going to happen.

I think that right now there is going to be a Phase 3 study. I don’t know if it has already started that is comparing isatuximab with pomalidomide and dexamethasone to pomalidomide and dexamethasone in the relapsed multiple myeloma. I think that the more drugs we have, the better. Could one CD38 antibody work in one patient and the other not? Theoretically, if one doesn’t work, the other one shouldn’t work either because the mechanism of action is similar. But really to know that, there should be a clinical trial because you can test as many things as you want in cells and cell cultures, but then you don’t really know until you try it in the patient.

I think it’s going to be difficult to answer the question of which one is better or are they similar, how similar they are because I’m not sure there is going to be a head-to-head comparison of the two drugs. But in the clinical trials, they both have a good activity. So isatuximab, a single agent, had a response rate of 20% to 40% depending on the lines of treatment which is pretty good for single agent for relapsed type for isatuximab, and daratumumab has similar responses and then with the addition of lenalidomide and pomalidomide, even more better responses. I think that at least it looks as good as daratumumab. I think it’s better for patients to have both available.

Jenny: Yeah, they have some options. And this one is by Sanofi, right?

Dr. Manasanch: Right. Sanofi (Isatuximab),  daratumumab is Janssen.

Jenny: In your study, you have three arms of dosing. You’re going to try three different ways, but this is a Phase 2 study. Do you want to describe the study in general, how it works and then how people can join or just basically how it works?

Dr. Manasanch: This study actually everybody gets the same dose. So with only one arm is 61 patients and what we’reetargeting here is a response rate. We would really like about 70% of the patients to have at least a partial response. That’s the target that we put as we are talking to the Food and Drug Administration. That’s the target that we could to consider this a good treatment. There is only one arm. Everybody gets the isatuximab every week for the first couple of months. The first two months is every week. That’s why if don’t live in Houston or you’re not close around Houston for this study or New York, it’s difficult because you would have to travel back and forth once a week for two months.

Then it goes from starting with the third cycle so month three, four, five and six for four months, then it’s every two weeks, then infusion of four, five hours every two weeks. And then starting with cycle number seven, so after the first six months because every cycle is 28 days then starting with the cycle seven, and it can go up to cycle 30 so we can go for another two years of treatment, you get it once a month. And then whether you get it for two and a half years or you’ll only get it for half a year, it depends on your response. If you have a very good response, you can keep getting it. If you don’t have a very good response, you can elect to go off with the study. This study is very early on.

We have a couple of patients that started. One hasn’t finished cycle one. The other one has finished a couple of cycles, and she already has a minor response. So that’s very interesting. And another thing is we actually also completed a smoldering study with another antibody called pembrolizumab which is another mechanism of action. And we saw a patient who had a complete remission. So they can work but it’s so early on. We really are trying to put pieces together, but we’re also at the level of designing new studies.

For isatuximab, it seems very promising, usually very well tolerated. You don’t lose your hair. Most side effects are very low grade. They do have some side effects but it’s not much. It depends on the patient, but some patients had a little bit of dry eyes. One patient had an infusion reaction, but he probably was in need of extra pre-medication and once that extra pre-medication was given, that didn’t happen again. I think that they are usually very well tolerated. Then the study goes on for about two and a half years but again it depends on how well you respond.

Jenny: And you’re saying that this is appropriate in high risk smoldering myeloma because it’s an antibody, number one, and you said your goal is to try to provide immunotherapies for patients so they’re not as toxic. Are there other reasons that you chose isatuximab in high risk smoldering myeloma?

Dr. Manasanch: Well, so the first thing is I even wanted to do it in intermediate risk because intermediate risk is even 50% at five years which I think is a lot. If you have 50% of myeloma in five years, to me, that sounds like a lot because myeloma can be very devastating. I want it even to do it a little bit earlier but we have discussed it with the FDA, and the FDA wanted this to be done in high risk. So that’s one of the reasons it was only high risk. I would have been okay doing it. Also, people who have a risk for 50%, I still think that 50% is a lot. The main reason to choose high risk is because those are patients where you can make a bigger difference, right? Because let’s say you have a patient who is low risk and they have 25% at five years.

You are treating 75% of patients that are not going to progress in five years. But if you take the 75% who seem they are going to progress, you know that 75% of the patients you are treating, they would progress or they have higher chances of progressing. The benefit seems to be greater here because they would progress regardless and you are trying to do an intervention. Also, you can see results sooner because if you take 50 patients with MGUS that have very low risk of progression to myeloma and then you treat them, how do you know you’re going to see it? You know, you could wait 30 years to see a difference, right? Because they may not progress. But if you take people who are high risk, who have a 75% chance based on the current criteria to have myeloma in five years then at five years, you can analyze this patient and if you say only 20% progressed, I mean that’s a big difference. So that’s an easy way to show it after five years. You don’t have to wait forever in 30 years. That’s an easy way to show that a medication is working or that is potentially very important for a disease state. So that’s one of the reasons to choose this.

Jenny: Right, I think it’s great. I’m excited that you’re doing this study. Well, I know I have taken a lot of time. I want to leave it open to caller questions as well. So, let me do this. We’ll open it up for caller questions and if you have a question for Dr. Manasanch, you can call 347-637-2631 and press 1 on your keypad. And then if we have extra time, I’ll ask some follow-up questions, but I want to make sure that we do this before we have to go. Okay, our first caller, go ahead with your question.

Caller: Hi, Jenny. Hi, Dr. Manasanch. It’s such a pleasure to talk to you in person, so to speak, because I know we follow each other on Twitter. Thanks so much for doing this, this interview. It’s just been fascinating to listen to. Is this similar or continuation of the work that you did while at the NIH, the observational studies that Dr. Landgren had?

Dr. Manasanch: Yes, definitely. First of all, I want to say, of course, thank you very much to you for following on Twitter, for being an active member and patient advocating the myeloma community. We always need a lot of people like that. And then I also thank a lot Dr. Landgren, and I have to say that the person who taught myeloma to me was Ola Landgren. He’s very cherished in my heart and a great investigator, great myeloma doctor. If he listens to this at some point, hello and hope everything is going well right now. But, yes, this study in a way is similar to the study that Dr. Landgren was doing at the NIH and because I was involved in that, I was able to start here and do something similar.

However, there are some differences, the technologies have changed so much because some of the studies that Dr. Landgren was planning to do on his studies are different from the ones that we’re planning to do because also, for example, we have a lot of immunology expertise here, so we are taking advantage of that to do a lot of immunology studies. We also have a lot of expertise with genomics. We have a very important genomics core. We have a lot of things. Some of the things are different and the study also has less patients. I think his study had more patients. It’s similar but it’s a little bit different mostly on the correlative studies, what were are goint to test, what we’re looking for and so on.

But, yes, Dr. Landgren, it’s a very good thing what he is doing. I believe he has all the samples.  I think that he has collaborations with other institutions and doctors and companies to look into those samples. I’m looking forward to see if something comes out of that. But I’m staying here for the foreseeable future. Hopefully, we’ll have a lot of data and a lot of followup. So that’s the most important. If you leave, sometimes you cannot take the samples with you or things like that.

Caller: Doctor, I realized that you stated that only MD Anderson patients would be eligible and that makes perfect sense to me because of the fact that you have to provide the samples. But is there any thought on your end to extend it beyond MD Anderson and find a way for patients to be able to submit blood samples to you or bone marrow biopsy samples? And the reason why I’m asking is that Dr. Ghobrial at Dana Farber has her P-Crowd Study in which we do that. It’s an observational study. I’m part of it and I live in New York. At my regularly scheduled lab draws every quarter, I have three little extra vials that I fill up and I send it to them by FedEx. They send me an envelope, I send it back to them, and they are able to actually use my serum for their study. I have done the same with bone marrow biopsies whenever I had one regularly scheduled. Is there any way that MD Anderson might expand in order to get your study accrual going?

Dr. Manasanch: First of all, let me say that I’m fascinated by Dr. Ghobrial. She’s amazing. When you go online and you see all the things for the P-Crowd, I mean it’s absolutely the moment of revelation. We actually are doing quite well on study accrual for this study. And then, yes, I would love to do that if we had the resources. Right now, right this minute or in the next two or three months, I don’t think it’s going to be possible just because of all the organization that this would require. I am not saying, you know, we may not do it in a couple of years. One of the things that we also do here, first is we have patients at the MD Anderson, right?

Caller: Yes. It’s a very large institution, so I’m sure you won’t have a problem on accrual.

Dr. Manasanch: Yes. Let’s see how many myeloma doctors we have. We have probably six or seven myeloma doctors and we have clinic where we see 20 patients a day. Each of us has 50, 60, 70 patients every week, so that’s hundreds of patients every week that we see. So then we have something called the myeloma tissue bank study. In that study, any patient with anything, even if you have MGUS or smoldering or myeloma or even if you have amyloid, patients with Waldenstroms, once you come in, you can sign a consent where every time you have a bone marrow or you have blood done because your doctor thinks that is necessary to do that, then we take a little bit of sample. We have quite an tissue bank but I’m not saying no. I think right now we have quite a lot of samples. I think you will be a great idea and I would love to do that, but I would have to see how I can do that.

Caller: No, I understand that it’s an undertaking. It certainly is.

Dr. Manasanch: It’s an undertaking. That’s why I think she’s my hero.

Caller: I know. She’s amazing. I have a smoldering myeloma Facebook group and she was very, very supportive and she joined it. We did like in-group discussions about her work and whatnot. We generated a lot of excitement over her study. We were able to get a lot of patients for her that way. When you’re ready, come and join us too.

Dr. Manasanch: I’m ready. I’m ready to go right now.

Caller: Good. Jenny will send you the information, and she’ll send you the link because we would love to have you. We have a couple of your other colleagues as well, and it’s just really been a great resource. Can I ask you, though, about the trial that you’re doing now? Jenny, am I taking up too much time? Do you have other callers?

Jenny: Yes, we have one other caller.

Caller: Okay. I’ll just ask this quick question. Regarding the isatuximab trial, why is it only one arm? I’m curious because I know the dara trial had the three arms with different dosing. One arm was just eight weeks and then another arm was something else and then the third arm is similar to what your trial is going to be, the whole gamut. Have you looked at the dara results to determine that that’s probably the best type of approach to take or the best arm to use going forward with your trial since this is also an anti-CD38 monoclonal antibody?

Dr. Manasanch: First of all, great questions. And also let me tell you that we would love to have some of your colleagues that have smoldering myeloma to come join us for the isatuximab study so that being said, and I’ll be happy to join your group and do a session to explain more things about the study and give more details if they want to come and do a screening test with that.

Caller: Great.

Dr. Manasanch: Now that being said, with daratumumab, I do not know the data for the daratumumab study. I think the reason they did three doses is because they didn’t know what dose was going to be better for Janssen, the company. But Sanofi, they waited a long time to have a dose that they thought would be the best dose and it’s based on a dose from relapsed myeloma. But they spent a lot of time doing the Phase 1 study, on Phase 1 and Phase 2 studies to see, depending on the pharmacokinetics and pharmacodynamics, what will be the best dose. So then they decided that this is a dose where the receptors, the CD38 receptors, are saturated and they decided on just one dose. That’s why this study in just one arm because that’s the dose they decided. That’s the dose they wanted to explore. So they already have that dose.

Caller: Okay. That makes sense.

Dr. Manasanch: Yes. That’s the reason why.

Caller: If a patient, let’s say, were to progress or show signs of progression on it, once they switched to the monthly part of the protocol, are you able to dial back and get them back on, let’s say, every other week or is it a really rigid study and that’s it. They are only monthly and they have to either continue with the study or drop out of it.

Dr. Manasanch: The way the study is being done right now is that if you are on the once monthly and you progress, you have to come off the study. However, because there is an investigation initiated study, we control the study. We (MD Anderson) actually holds the MD Anderson holds the new drug application for this study, so we have some leeway. If we see or we think that it might be better for patients to be able to receive the drug again every week, then we may amend the studies, talk to the FDA about this.

Caller: So you have that wiggle room.

Dr. Manasanch: We have wiggle room. We can change the study because I wrote the study, so I can change it. If I think something is going to be more beneficial for the patient, I can change it. I have to discuss it with the FDA and there has to be a rationale and I have to explain why. But the FDA, if you have a good rationale, they usually say yes.

Caller: Well, that’s exciting to know. Jenny interviewed Dr. Orlowski a couple of months ago, and we were talking about daratumumab and how it tends to begin to lose its effectiveness. He mentioned that it could be due to two reasons — loss of CD38 expression and maybe even a T-cell exhaustion kind of scenario. Would you also theoretically think that you could see this in smoldering patients too?

Dr. Manasanch: It’s possible, yes. I mean it could happen that you could have the CD38 downregulation and it could happen that these T-cells or NK-cells then attack the cells. It could not be as effective. But we don’t know that, right?

Caller: Right. That’s all theories.

Dr. Manasanch: Yeah. It could happen but that’s why we are doing the studies. And then also it’s possible like you have to saturate the receptors, the CD38 receptors, and you have to have very bright CD38. That’s how these antibodies work the best. So yes, those are the mechanisms of resistance to these antibodies. Unfortunately, the later stages are not usually curing people, right? But let’s see what happens in the early stage. I mean, we’ll have to look at the data. But yes, those are potential complications that could happen with a treatment.

Caller: So you’re doing it in Houston and you’re also doing it then in two locations in New York –  at Sloan Kettering under Dr. Landgren and then in Mount Sinai under Dr. Jagannath and Chary.

Dr. Manasanch: Yes, but they’re not open yet.

Caller: They are not?

Dr. Manasanch: No, because our protocol, we have been doing amendments on our IRB. We just reviewed it, so now we’re going to send the protocol to New York and then the New York IRB has to approve it. Once the New York IRB approves it, then they can start. It might still be maybe between one and three months, I’m thinking.

Caller: Great. Well, thank you so much. I appreciate all the time that you afforded me. I appreciate it. And Jenny, if you can give Dr. Manasanch the link to our Facebook group, we’ll work on talking about her study.

Jenny: Great. Okay. Thanks, Dana. Okay. We have another caller, go ahead with your question.

Caller: Hi. Yes, this Joan and I don’t know if you remember me from NIH. I was in this high risk smoldering CRD protocol back in 2012-2013.

Dr. Manasanch: Yes, of course.

Caller: Okay. I was so excited when I saw this. Actually, another patient sent me this that you were going to be doing this. I just want to let you know that I am — well, actually, I have a six-month followup at NIH tomorrow, so we’ll see how that goes.

Dr. Manasanch: Who are you seeing? Are you seeing Kazanjian? Who are you seeing there?

Caller: Yes, that’s who I’m seeing, Dr. Kazanjian. If I needed anything, if I see Dr. Kwok over at Walter Reed is my doctor. If you remember Mary Kwok.

Jenny: Yes. Can you say hello to them? Of course, they are both dear friends.

Caller: I will. What I do is one quarter I see Dr. Kwok, so I saw her in January. This time I’m seeing Dr. Kazanjian. And then I’ll see Dr. Kwok again in July and then in November, end of October, I’ll go back to NIH and they’ll do another bone marrow biopsy and a PET-CT scan. That’s what I have been doing since I finished up with the two-year maintenance with the Revlimid. But so far, things have been going pretty good. I’m just very happy that I did the trial, and you really were my doctor at the beginning of all this for me during most of my treatment time. I was just thrilled to see this and everything that you’re doing down at MD Anderson sounds really exciting. Do you see a time where you think that the treatment for high risk smoldering will not be strictly under trial circumstances where it will be considered to be a treatment that will be able to be done outside the trial area?

Dr. Manasanch: Yes. I think that’s where we’re going. That’s why there are so many studies. Again, the NIH study was a small study, had excellent results, as you know for yourself, right? You did so well. But yes, there are two issues that I think need to be solved a little bit before this can be given, for example, in the community, right? Because most patients who have smoldering myeloma and myeloma, they are not treated at NIH or at Sloan Kettering or here. They are treated in the community, and so we have to be very mindful of what we recommend because the tools that we have here, they are not available in the community. The doctors in the community sometimes cannot make decisions on what’s high risk, what’s not high risk because they don’t have the tools.

Our job is to make some criteria that you can reproduce in the community, in academic centers that a doctor in the community can use, that is easy and reproducible, something similar to a yes or no answer, if possible. And then if we have something where we can identify the patients that are going to progress very well and we can give that pass and say, okay, you have very high risk so then this will be the treatment. And then we have to have a large study comparing one treatment that we think might be the best treatment to something else. I think those things have to happen and we are not there yet.

The danger with smoldering is that it’s possible that patients that are very low risk are going to be treated because the tools to assess who is at high risk sometimes they are vague. There are different types. Sometimes by one criteria it’s high and another is low. We really need to have a very big consensus on what’s high risk. It’s not there yet. I mean I know that, for example, the IMWG is working on it, but we’re not there yet but it’s the next step. It’s going to happen and it’s going to happen in my lifetime that —

Caller: Well, I will hope so. I mean I think it’s wonderful and I never had a moment’s regret for having done the trial and was really happy that I happen to be in Dr. Landgren’s — I forget the name, the natural history trial that he was doing which is how I got connected up at NIH. I hope to see that done, and it’s really exciting to see things that you are doing there. I’m pleased. I was so thankful that I got to see you a lot and you helped take care of me when I was at NIH for my treatment. But I just wanted to wish you well and I will let Dr. Kwok and Dr. Kazanjian tell them hello for you. I’ll see Mary in July, and I’ll see him tomorrow. But thank you very much and good luck with everything that you’re doing. It’s really exciting, and it’s wonderful to see all the different treatments that are out there for everyone.

Dr. Manasanch: Thank you so much. It’s very nice to hear from you.

Jenny: Thanks for your comment. Okay. We have one more caller, go ahead with your question. This is our last question.

Caller: Hello, doctor. I was wondering if somebody had the resources to come to MD Anderson and be part of the trial. Would you encourage them to do that if they were currently at a facility that didn’t do those trials?

Dr. Manasanch: Yes. I mean if they have smoldering myeloma, yes, they can come. We can do an evaluation. Of course, they have to have a high risk smoldering myeloma, so not everybody is eligible. But if you have high risk the smoldering myeloma, I mean unless you cannot have uncontrolled diseases, you can not have had another cancer within three years. But I mean, except for those things, most people should be eligible. So sure, I would encourage them to come. They can contact me. I don’t know if there is a way to give my email but definitely I mean we can see them in the clinic.

Caller: Well, sure, I appreciate that. Oh, go ahead. Go ahead.

Jenny: No, go ahead. Yeah, go ahead. I think she is talking about isatuximab trial also. I think even if you’re not high risk, you can still join the observational trial, right?

Dr. Manasanch: Yes.

Caller: Yeah, that’s why I was wondering. I have been talking over the past few months, I was diagnosed in January with smoldering myeloma and Dr. Ghobrial and her team have looked at all my results that I’ve had done and they consider me high risk, but the facility that I’m at right now considers me low risk so it’s kind of harder to discern.

Dr. Manasanch: Yeah. That’s what I’m talking about, exactly.

Caller: Yes. I can’t get up to Boston logistically, but we are close enough to Houston and have family there, so I have considered maybe coming down there in the next month or two. I didn’t know if that would be a good idea, so it’s good to know.

Dr. Manasanch: Yes. I mean if you want to give me later, I don’t know if there is another way we can communicate, then you can give me your information and we can set up an appointment. That’s totally fine.

Jenny: Sure.

Caller: Oh, yeah, that would be great. I don’t know if Jenny can do that out there.

Jenny: You can email me. So email me at info@crowdcare.org and then I’ll pass your email along to her.

Caller: Perfect, yeah. I have emailed you before, Jenny, so I’ll do that this afternoon for sure.

Jenny: Okay, great.

Caller: All right. Well, I appreciate both of you having this today. It was a wealth of information and really encouraged me in a lot of areas, so thank you very much.

Jenny: Well, thank you so much for calling in. Well, Dr. Manasanch, we are way over time but I’m still thankful that you held on the line for us and answered all these important questions. We are just really happy with what you’re doing at MD Anderson and just wish you all the best. I think some of these callers are just examples of the benefits of participating in clinical trials. I think people that are looking to participate in clinical trials are more aware of the kind of disease that they have. They are better at tracking the disease. They are better advocates for themselves and, as you can hear, they ask a lot of important questions that are going to get them better outcomes. Thank you again for joining us today.

Dr. Manasanch: Thank you so much. This is my pleasure. And thank you for all you’re doing for all the myeloma patients.

Jenny: Oh, thanks. Thank you for listening to Myeloma Crowd Radio. Tune in next time to learn more about the latest in myeloma research and what it means for you.

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About Author

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.

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