Tag Archive for: carfilzomib

Expert Perspective | Understanding the Recent FDA CAR T-Cell Therapy Warning

Expert Perspective | Understanding the Recent FDA CAR T-Cell Therapy Warning from Patient Empowerment Network on Vimeo.

The Food and Drug Administration (FDA) announced in December 2023 that it is investigating reports of secondary cancers in some patients who have undergone CAR T-cell therapy, noting that “the overall benefits of these products continue to outweigh their potential risks for their approved uses.” Timothy Schmidt, a myeloma specialist, shares his perspective on the recent news.

Dr. Timothy Schmidt is an Assistant Professor in the Department of Medicine, Division of Hematology, Medical Oncology and Palliative Care at the University of Wisconsin School of Medicine and Public Health. More about Dr. Schmidt.

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Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023

Transcript:

Dr. Timothy Schmidt:

So, in terms of the FDA update about CAR T-cell therapies, there was a recent warning, essentially, about an increased risk for a specific type of lymphoma involving T cells. And we don’t really know a whole lot about this just yet. But what we do know is that these events are rare and that we need to investigate it further. I think as of right now, this is not a huge area of concern for most of us, myself included. 

When we have patients who are candidates for CAR T-cell therapy in multiple myeloma, generally, this means that patients are in need of a very effective treatment to get their disease under control and to do so for a long period of time. And the potential benefit of this therapy dramatically outweighs any of these kinds of long-term consequences or these newer things that are starting to develop. Now, I do think that this is something that we’re going to need to continue to keep an eye on. And we certainly can’t ignore this, especially as we start to move CAR T-cell therapy into earlier lines of therapy. 

But as of right now, I would not weigh this very heavily in my decision whether to do a CAR T-cell therapy for somebody with multiple myeloma. 

What Should Myeloma Patients Ask About Developing Research?

What Should Myeloma Patients Ask About Developing Research? from Patient Empowerment Network on Vimeo.

Myeloma research is evolving quickly, so what should patients ask their doctor to stay up to date? Dr. Timothy Schmidt, a myeloma specialist, shares advice.

Dr. Timothy Schmidt is an Assistant Professor in the Department of Medicine, Division of Hematology, Medical Oncology and Palliative Care at the University of Wisconsin School of Medicine and Public Health. More about Dr. Schmidt.

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Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023

How Is Bispecific Antibody Therapy Changing Myeloma Care

How Is Bispecific Antibody Therapy Changing Myeloma Care?

Myeloma CAR T-Cell Therapy_ How Does It Work and What Are the Risks

Myeloma CAR T-Cell Therapy: How Does It Work and What Are the Risks? 

Transcript:

Dr. Timothy Schmidt:

I think that in terms of new and developing options, patients should be asking their healthcare provider, their oncologist if they have experience using some of these newer drugs, specifically, the bispecific antibodies and CAR T-cell therapies. 

A lot of centers are starting to use these, particularly academic centers and some larger community centers as well. But not everywhere has experience using these. And so, asking your provider if it’s something that they would be a candidate for, particularly if the current treatment that patients are on is not working. And if your provider is not necessarily familiar with them, do they know somebody who is.  

And could you go at least for a discussion to talk to a myeloma specialist about whether these medications are right for you or whether there’s a clinical trial that they might be a candidate for, because what we’ve learned is that earlier implementation of some of these really effective therapies can really be a big deal for patients with myeloma. 

Patients can learn more about clinical trials from a variety of different outlets. I think the first place to start is with your local provider, your oncologist, asking that person if there is a clinical trial available. Most likely, the local provider is going to be able to point the patient in the right direction or at least let them know if something is going to be feasible for them. After that, often it involves reaching out to a local center, an academic center and getting a referral to somebody to see what is available at that site.   

But there are also a variety of websites that can be used to search for clinical trials if there are particular patients who are very interested in specific therapies, CAR T, bispecifics, or others that you can look around and try to find places that would be best for them. 

Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023 from Patient Empowerment Network on Vimeo.

Dr. Timothy Schmidt, a myeloma specialist, walks through research and treatment news from the recent 2023 American Society of Hematology (ASH) annual meeting.

Dr. Timothy Schmidt is an Assistant Professor in the Department of Medicine, Division of Hematology, Medical Oncology and Palliative Care at the University of Wisconsin School of Medicine and Public Health. More about Dr. Schmidt.

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What Should Myeloma Patients Ask About Developing Research

What Should Myeloma Patients Ask About Developing Research?

Expert Perspective | Understanding the Recent FDA CAR T-Cell Therapy Warning

Expert Perspective | Understanding the Recent FDA CAR T-Cell Therapy Warning

Developing Research and New Myeloma Treatment Options

Developing Research and New Myeloma Treatment Options

Transcript:

Dr. Timothy Schmidt:

So, there’s constantly a lot of new information and data coming out about multiple myeloma and new therapies. I would say at this ASH ’23 meeting, I think the biggest highlight is further confirmation of the utility of using CD-38 antibodies in patients with newly diagnosed multiple myeloma. We have a plenary abstract for the use of isatuximab (Sarclisa) in combination with carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Decadron) that I’m anxiously awaiting hearing the data of later today, as well as a late breaking abstract talking about the use of daratumumab in combination with bortezomib (Velcade), lenalidomide, and dexamethasone. 

And both of these are studies that appear to show superiority of a four-drug regimen over a three-drug regimen. And we’re certainly looking forward to seeing the finalized data presented and extending the implementation of these highly effective therapies for patients with newly diagnosed multiple myeloma.  

I think what we’re also seeing here is just further data being presented about bispecific antibodies, CAR T-cell therapies, and other novel combinations in the relapsed and refractory setting, as well as some really interesting insights coming out in terms of the myeloma pre-cursor setting of MGUS from the IStopMM Trial and some other research. So, really excited to learn more about how to use all of these exciting new tools that we’ve got for patients with multiple myeloma across the disease spectrum.  

So, what this news means for myeloma patients is that outcomes are getting better. What it means is that we now know how best to use some of these tools that we’ve been developing for over a decade now in terms of maximizing responses, maximizing the number of patients who achieve remission and not just achieve remission but have a lasting remission in that first-line setting. And this is really going to lead to improved survival as well as improved quality of life when we start seeing year upon year of really high-quality survival from most of our patients with multiple myeloma. 

We’re also learning how best to use some of the even newer therapies. T-cell directing therapies such as CAR T-cells and bispecific antibodies. We are incredibly excited about how effective these drugs are for patients with multiple myeloma. 

And these are things that we’re already using in the clinic. And it’s important for patients to be aware so that when it becomes time to use these strategies that we can make sure that all patients have access to them. 

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Making Treatment Decisions | Understanding Common Myeloma Therapies

Making Treatment Decisions | Understanding Common Myeloma Therapies from Patient Empowerment Network on Vimeo.

What are common myeloma therapies, and when are they used? Dr. Ashley Rosko outlines the factors that impact treatment decisions and reviews available therapies including stem cell transplant, proteasome inhibitors, immunomodulatory therapies, and monoclonal antibodies.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

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Advances in Myeloma Treatment: CAR T-Cell Therapy and Bispecific Antibodies

Advances in Myeloma Treatment | CAR T-Cell Therapy and Bispecific Antibodies


Transcript:

Katherine:

We know that multiple myeloma patients have a number of options and that many available therapies are used in combination. 

So, I’d like you to walk us through the options that are available. 

Dr. Rosko:

So, I’m going to start by how the best way that I can frame out when we talk about newly diagnosed versus patients when they have relapse. So, there are therapies that are available for patients that are FDA-approved when they are newly diagnosed with the cancer, and there are therapies that are approved only when a cancer has acted up again or relapsed. 

So, I’ll kind of frame it from patients who are newly diagnosed. And then, I also will talk more about relapsed therapies and what we’re able to offer to patients. So, in first, when we talk about treatment options, we frame treatment based on a couple things. So, one is, we talk extensively about the disease biology. So, that plays an important role in how we decide which treatment the patient should get. 

And then, the second part about how – I would probably say there’s about four main parts. And so, disease biology is one, and another thing has to do with the patient characteristics. In terms of the patient’s overall health prior to developing cancer, and also how the cancer has impacted their health in terms of everyday activities. Whether or not a person has really slowed down quickly, whether they’ve been in the hospital, and how it’s impacting their organs. Because that plays a role in terms of what we’re able to give patients.  

If a patient has advanced kidney failure, which can sometimes happen, or if you have to focus more on protecting their bones and if there’s concern about fractures and things like that. And then independent of patient characteristics in terms of overall health, the last part I talk to patients about is their own preferences. It’s a hard thing to talk about, shared decision-making in a cancer that most people have never heard about, but there is certainly – when we talk about options and there are, it’s important to talk about shared decision-making in terms of what’s most important to them and where they – and most patients will say, “Well, I just want the best medicine.”  

And I say to them, “Well, you know, we have lots of options, and that’s the best thing about it, but we also want to be cognizant of the real world, of giving best options,” and for example, Many of my patients – so, I’m at The Ohio State University, I’m here. And a lot of patients travel. I have a lot of older patients that I care for, and they’re very independent with travel. And I want to make sure that whatever therapies we’re getting for them, that we can do this in such a way that maintains their lifestyle.  

So, the beginning part of a treatment, it is broadly described as – when we talk about someone who was diagnosed with this, it’s this thing called induction. So, induction is when we give anywhere from two to four medications to be able to control their cancer and put it into remission. And we know that the cancer is in remission because, like we started out the conversation with Dr. Cottini, myeloma makes proteins. Oftentimes, it makes proteins, those proteins are not nutrition proteins but are cancer proteins that we can track in the blood. 

So, we can check them every month and to make sure that the patients are having a really good response, and as such, we’re able to define that they’re responding to their treatment. Because they have a beginning stage in induction, which they’re given treatment, and then the goal is to put patients put in remission.  

Depending on the overall health of the patient, a standard of care for most patients diagnosed with multiple myeloma is to undergo an autologous stem cell transplant. An autologous stem cell transplant is not a transplant in which you’re getting cells from your brother or sister and they’re being donated to you. They are your own stem cells. We get them out of you when your bone marrow is free of disease, and then we would admit you to the hospital for a more intensive therapy and give them back. 

That is often the standard of care for patients newly diagnosed with multiple myeloma, and it is recommended for most patients. Some patients get – I like to think of it as a stem cell transplant not at the time of their initial diagnosis, but later on at the time of relapse, or some patients are not candidates for a transplant or elect not to have a transplant. And all of these options are very personalized to the patient. It’s very hard to say that this is exactly what we do. 

Because it’s a strategy where it requires a lot of shared decision-making to make sure that we’re getting good disease control, good quality of life, and deep, deep remissions for our patients. So, then, if a patient gets a transplant, there’s a period of recovery, and then patients go on a pill most often, a maintenance pill that they stay on for indefinitely. 

Myeloma is also a cancer which has perpetual therapy. Very different than many other cancers, where there’s a beginning and an end, myeloma for the most part is perpetual therapy, where you get some form of therapy at higher dosages versus lower dosages over a period of time.   

So, I’m going to talk broadly about the classes of drugs that we have and how we use them to be able to define therapy. 

So, the first class of drugs are called proteasome inhibitors. Just like many other cancers, we use different types of drugs to be able to target different aspects of a cancer cell’s growth cycle.  

So, very similar to how we do other drugs, these are very specific to the cancer cell, and they’re very targeted. So, unlike some of our other kind of classic chemotherapies, many of these medicines that I’m going to talk about are very targeted at the cancer cells without causing too many other problems. 

So, proteasome inhibitors include drugs like bortezomib (Velcade), which is given as a shot, carfilzomib (Kyprolis), which is given as an IV, or ixazomib (Ninlaro), which is given as a pill. They have different indications, but they’re the same class of drugs.  

The next class of drugs is called immunomodulatory drugs, or iMiDs. This includes things like lenalidomide (Revlimid), pomalidomide (Pomalyst). Those are the most common, and then we sometimes use the drug that the original iMiD drug, which is called thalidomide (Contergan). 

These are all pills that patients take, and so that’s oftentimes very nice for patients to be able to provide therapy at home, very well-tolerated. The next class of drugs are called monoclonal antibodies. On a cancerous cell, there is a marker. 

And so, we use monoclonal antibodies to be able to target the marker on the cancer cell. What that means is very specific. To that cancer cell, so, the most common target is the CD38, that’s a marker on one of the cancer cells. And we use a drug called daratumumab (Darzalex), that can be given as an IV or a subcutaneous agent, or another drug called isatuximab (Sarclisa). We also have other markers on the plasma cell. There’s a marker called SLAMF7, which we have other drugs called elotuzumab (Empliciti), which is often used for patients more in the relapse setting. 

How Do Myeloma Test Results Influence Prognosis and Care?

How Do Myeloma Test Results Influence Prognosis and Care? from Patient Empowerment Network on Vimeo.

Key testing is important for understanding myeloma, but how do results impact care and treatment? Myeloma experts Drs. Ashley Rosko and Francesco Cottini discuss how test results can affect care options and encourage patients to discuss results with their healthcare team.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.
 
Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

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Making Treatment Decisions | Understanding Common Myeloma Therapies


Transcript:

Katherine:

Dr. Rosko, what do the results of these tests tell you about prognosis? 

Dr. Rosko:

Yeah, I think this is a really important question. And, in my experience, when we encounter a patient newly diagnosed with myeloma, it is like drinking from a firehose in terms of the amount of information that we are reviewing and the amount of information that we are discussing with the patient and with their family. And oftentimes, we talk about this piece of these cytogenetic abnormalities, and we talk about – but I really encourage your patients and anyone who is listening in today to really take a deeper dive. 

Because sometimes it’s helpful as, one, you’re navigating a new cancer diagnosis, but that’s challenging in and of itself. And then, two, talking about a cancer, multiple myeloma, that is – most people don’t know so much about multiple myeloma, unlike breast or colon or lung cancer, and so I really encourage patients and their caregivers. And a lot of times this happens, where we’ll go over all the cytogenetic abnormalities, we’ll talk about how it plays a role in their overall treatment trajectory, and their prognosis, but also good just to circle back and say. 

Settling into what this diagnosis is, oftentimes, people on first time treatment. And then even sometimes months or even years into their diagnosis, they stop and they come back and they say, “Can we talk about this FISH data?  

Can we talk about what changes that I had within the DNA? What does this mean?” And that’s not uncommon at all.  

So, I really feel like for many people that are on the call here today, I think it’s important to say it’s okay to go back to your physician and say, “I’m learning more about this, now that I’m more familiar with what this diagnosis is, can we talk about these FISH changes, or can we talk about the stage of my cancer?” Because I think it’s oftentimes an overwhelming period of time to have a new cancer diagnosis. And I also want to just give permission to everyone on the call that it’s okay to go back and ask questions, even if it’s been months or years.  

So, having high-risk mutation can upstage a cancer and in the absence of high-risk mutations can downstage a cancer. So, what that really means is saying, “These biologic changes that are happening in the cancer cells give a sense of what we anticipate that the trajectory is going to be when someone is diagnosed.” 

Now, it’s imperfect. I feel like cancer just generally is unpredictable, and there are many things that we try as clinicians. And especially with the experience that we have, to say, “This is what we anticipate the course will be like you, in terms of response, in terms of the cancer being quiet.” As you all know, multiple myeloma is not a curable cancer right now. And for all patients, when they’re diagnosed, they’re often able to get disease control and be able for that cancer to be put in remission. And we do focus on remission. 

I think that’s also something that I talk to my patients about. Even though we can’t cure it, we can certainly control it, and that’s a big part of what we do. So, when we get good disease control, we’ll talk more about next therapies, but that is how Dr. Cottini – Dr. Cottini is a wonderful scientific investigator and knows all of the latest and greatest when it comes to different mutations that are identified within cancer cells. We partner very closely with her in terms of  scientific investigation and how the mutations that were newly identified, too, play a role in terms of response to treatment, and how we’re able to best treat them. 

Katherine:

Thank you for that. Dr. Cottini, do you have anything to add as far as what type of questions patients should ask their healthcare team about test results?  

Dr. Cottini:

I mean, I think Dr. Rosko already pointed out the most important things. So, multiple myeloma is a rare disease, and it’s not as intuitive to understand as breast cancer, lung cancer, prostate cancer. 

So, it’s really important as a patient to understand which tests are we ordering. Why are we ordering? How do we monitor the disease? Because that’s one of the most important questions the patient asks, because for different types of solid tumor, we get imaging, and we know that the tumor is growing or not. Where, for us, we look at the markers I had described previously. And sometimes, we maybe see small changes in the markers that are very concerning and worrisome for the patient, but sometimes they are not. So, I think asking questions about the testing and how we treat them and monitor the disease is a very important part of being a good applique for itself.  

Accessing Personalized Myeloma Treatment | What Patients Should Know

Accessing Personalized Myeloma Treatment | What Patients Should Know from Patient Empowerment Network on Vimeo.

Myeloma experts Dr. Francesca Cottini and Dr. Ashley Rosko provide an overview of the latest advances in essential testing for myeloma and explain how results could affect care and treatment decisions. Drs. Cottini and Rosko also review available myeloma therapies and their hopes for the future of patient care.

Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

Dr. Ashley Rosko is Medical Director of the Oncogeriatric Program at the Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Rosko.

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How Does Essential Testing Affect Myeloma Care and Treatment?


Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to discuss how to access personalized care for your myeloma and why it’s vital to insist on essential testing.  Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Let’s meet our guests for today. I’ll start with Dr. Ashley Rosko. Dr. Rosko, welcome. Would you please introduce yourself? 

Dr. Rosko:

Hi everyone. My name is Ashley Rosko. I’m an associate professor at the division of hematology at The Ohio State University. 

I’m also the medical director of the oncogeriatric program here at The James and one of the myeloma physicians here at Ohio State. 

Katherine:

Thank you. Also with us is Dr. Francesca Cottini. Dr. Cottini, would you please introduce yourself to the audience? 

Dr. Cottini:

Sure. My name is Francesca Cottini. I am an assistant professor in the divisions of hematology at The Ohio State University. I see patients with multiple myeloma, and I also run my own lab where I focus on multiple myeloma basic research. 

Katherine:

Thank you both for taking the time out of your busy schedules to join us today.  

It’s no secret that it’s important for patients to take an active role in their care and treatment decisions, and I’m sure many viewers here today are doing just that. So, Dr. Rosko, let’s start with this question: Why do you think it’s essential that patients advocate for themselves and insist on better care?  

Dr. Rosko:

Yeah, so I think when it comes to uncommon diseases like multiple myeloma –  

Although we’re talking a lot about it here today, myeloma is an uncommon cancer, and when it comes to rare cancers, it’s really important for you to get care at either a comprehensive cancer center or a place where there is expertise specifically in multiple myeloma. 

And the reason why that’s so important, it’s recommended through the NCCN guidelines and other standing guidelines is because myeloma is a very – it’s a shifting and changing landscape when it comes to both treatment regimens, diagnosis, and there’s a lot of moving parts and pieces.

Such as, there is an uncommon cancer that when diagnosed, we do recommend that patients and with their caregivers and with their families and support be able to seek expertise care for these uncommon cancers. We work often in collaboration with our community team, but we would not be able to care for myeloma if it were not for our community partners. 

And so, it’s really, really important for patients oftentimes, when there’s been such a diagnosis, they can come to a comprehensive cancer center for a consultation or to be able to get a second opinion oftentimes. And then continue to get care locally. It really provides this overall guidance on the management and diagnosis of uncommon plasma cell disorders, and we’re happy to do that. 

Katherine:

Thank you for that. It’s helpful as we begin our discussion. Part of accessing more personalized care starts with test results. Dr. Cottini, what testing should take place following a myeloma diagnosis?  

Dr. Cottini:

So, once somebody is diagnosed with multiple myeloma, there are different types of tests that we need to get. Some are blood tests, some are urine tests, some are bone marrow tests, and others are just different types of imaging. So, the reason for all these tests is because multiple myeloma can kind of go everywhere and can cause the damage to different types of organs. 

So, if we look at blood tests, usually you would see that you get the complete blood count, so we can count the number of red blood cells, white blood cells, and platelets. And then we’ll look at kidney function, through a chemistry profile, calcium levels, multiple myeloma can affect bone cells can affect kidneys. And then, you will see some more sophisticated tests that are really important for the diagnosis of multiple myeloma but also for monitoring and seeing if you’re actually responding to the treatment or you are progressing. 

These two tests that you can see are kind of difficult to say, but very important and needs to be remembered. So, one is called serum protein electrophoresis with immunofixation. And the other one is free light chain assays. 

And the practicum with these two tests is we can identify the specific marker of the multiple myeloma cells and it is either something monoclonal protein or M-protein or kappa light chain numbers. And as I said before, these numbers can be monitored. So, in response to the treatment, they should go down. And then, unfortunately, if we see progression, they might go up again. 

And then, urine tests can also give the same type of numbers. Usually, we have our patient keep the urine for 24 hours, for a day, and we can see if there’s monoclonal proteins or light chains there, too. Then there is a least favorite test of all of them that is the bone marrow testing. So, this is very important for us, because it’s where most of the myeloma cells stay. So, we need to have a look at the bone marrow.  

We need like a piece of the bone and some of the liquid tissue to look at specific characteristics of the myeloma. And then, I said before, the myeloma can go to bones, so we need to kind of get some imaging of the bones. These are usually a set of X-rays – it’s called skeletal survey – to see if there is any area that is abnormal or at risk of fractures.   

Then, we are also looking at PET scan, which is a more sophisticated test that is based on sugar consumption. We know that myeloma cells and all cancers enjoy sugar, so with the PET scan, we can see visually where the myeloma cells are in the body.

Katherine:

What is cytogenetics? 

Dr. Cottini:

So, this is a really interesting question. So, cytogenetics, or FISH tests, are tests that practical tests allow us to look at the chromosomes of the multiple myeloma. 

So, everybody has 46 chromosomes, right? Multiple myeloma cells can have more of them or less of them. So, they can have – some myeloma cells have 17 chromosomes instead of 46. So, cytogenetics in the karyotype counts how many chromosomes there are. And then, there is another type of test that is called FISH test, or fluorescence in situ hybridization – I get all the difficult names – that practically look at specific area of chromosome. It can tell us if some areas of chromosomes are lost. That’s what you can read as deletions, or practically missing pieces of chromosomes.  

Or there are extra pieces of chromosomes. These are the amplification gains. Or if there are different pieces of chromosomes that stick together. And these are the translocational chromosomes. And all of these data are important for deciding for knowing how aggressive or difficult to treat the myeloma. 

Katherine:

Dr. Rosko, in many other cancers, we’ve been hearing about targeted therapies and immunotherapies. In some cases, a specific mutation or chromosomal abnormality may indicate that a particular treatment may be effective. Are we there yet in multiple myeloma care? 

Dr. Rosko:

Yeah, so, myeloma care is always a little bit different. So, myeloma, being a blood cancer, is different than other solid tumors and how we treat it is also a bit different. So, unlike solid tumors, in which we look at the size of a cancer and then if it’s in different places in the body. In multiple myeloma, it being a blood cancer, just by definition it’s throughout the body. So, we have to be able to estimate or stage cancers differently or stage myeloma differently. And it is based upon the cytogenetics that Dr. Cottini just outlined to you.  

So, to get back to your question, Katherine, I didn’t forget about, how do we define treatment, how are some of these therapies being defined specifically and personalized for persons with multiple myeloma? And we do do that. And it is based a lot upon the DNA of those cancer cells and whether or not they’ve acquired what I would call a standard-risk changes or whether or not they’ve acquired a biology that makes them tend to act more aggressively. Now, again, these DNA differences – not all cancers follow the book, and not all therapies are unique to these. 

But what it does help us to do as clinicians to say, “Well, we have standard risk mutations within these cancer cells, and then we can define oftentimes how many drugs a patient gets when they’re newly diagnosed. Just like many other cancers, our treatments for multiple myeloma can be a combination of pills or shots. And then, if patients carry mutations that tend to act more aggressively, we tend to be very aggressive with their upfront therapy. For many patients, we’d receive three medications. Patients with more aggressive disease biology may receive four medications. 

And it’s very unique upon many characteristics. It’s not only based upon the cancer cells’ DNA but also the health of the patient. The health of the patient really defines also the ability to tolerate treatment. So, many patients are – myeloma has a lot of heterogeneity to it, where some patients with myeloma can’t believe that they could possibly have this cancer. 

You know, it’s really kind of picked up subtly, with blood abnormalities. And then some patients with myeloma come into the hospital very very sick, with having kidney damage or having infection. And it runs the gambit between being asymptomatic really and having patients coming in quite unwell. That also influences our treatment decisions. So, when we think about the question about whether we have different immunotherapies or targeted therapies based upon the genetic changes within the myeloma cancer cells, the answer is yes, we do shape therapy that’s tailored around the type of abnormalities within the cancer cells. 

But unlike some cancers, where if the cancer cells carry a specific marker, we give a specific drug, that’s not quite where we’re at with multiple myeloma, in terms that providing therapy is saying, “If you carry this mutation, this is what you should get.” 

So, it’s a very long answer to say to you that we do personalize therapy based upon changes within the DNA, but we also base it upon how fit the patient is and how their health was prior to developing cancer. 

Katherine:

Thank you for that. Dr. Cottini, what mutations or abnormalities are you looking for? 

Dr. Cottini:

So, as Dr. Rosko said, and as I quickly previously mentioned, so there are different types of DNA tests that we can do. One is this FISH test, and that’s a standard test. It’s usually done practically everywhere. And it practically tells us if there are specific deletions or changes. 

And we don’t really have yet a specific medication that we know works for specific abnormalities. But all this information is important to decide, as Dr. Rosko said, number of drugs, and maybe that can be helpful in the future when hopefully thanks to the research, we will be able to say, “Based on this abnormality, you would benefit more from this type of treatment.”  

There are other types of tests. One is called DNA testing, so we look at the mutation. So, really to point to small changes of a particular gene. This is done not routinely, but I think it can still give lots of good information. And there are lots of genes that are normally myeloma, that has potential drugs that have been studied, those with multiple myeloma and any other type of cancer. 

Katherine:

Yeah. Dr. Rosko, what do the results of these tests tell you about prognosis? 

Dr. Rosko:

Yeah, I think this is a really important question. And, in my experience, when we encounter a patient newly diagnosed with myeloma, it is like drinking from a firehose in terms of the amount of information that we are reviewing and the amount of information that we are discussing with the patient and with their family. And oftentimes, we talk about this piece of these cytogenetic abnormalities, and we talk about – but I really encourage your patients and anyone who is listening in today to really take a deeper dive. 

Because sometimes it’s helpful as, one, you’re navigating a new cancer diagnosis, but that’s challenging in and of itself. And then, two, talking about a cancer, multiple myeloma, that is – most people don’t know so much about multiple myeloma, unlike breast or colon or lung cancer, and so I really encourage patients and their caregivers. And a lot of times this happens, where we’ll go over all the cytogenetic abnormalities, we’ll talk about how it plays a role in their overall treatment trajectory, and their prognosis, but also good just to circle back and say. 

Settling into what this diagnosis is, oftentimes, people on first time treatment. And then even sometimes months or even years into their diagnosis, they stop and they come back and they say, “Can we talk about this FISH data? Can we talk about what changes that I had within the DNA? What does this mean?” And that’s not uncommon at all.  

So, I really feel like for many people that are on the call here today, I think it’s important to say it’s okay to go back to your physician and say, “I’m learning more about this, now that I’m more familiar with what this diagnosis is, can we talk about these FISH changes, or can we talk about the stage of my cancer?” Because I think it’s oftentimes an overwhelming period of time to have a new cancer diagnosis. And I also want to just give permission to everyone on the call that it’s okay to go back and ask questions, even if it’s been months or years.  

So, having high-risk mutation can upstage a cancer and in the absence of high-risk mutations can downstage a cancer. So, what that really means is saying, “These biologic changes that are happening in the cancer cells give a sense of what we anticipate that the trajectory is going to be when someone is diagnosed.” 

Now, it’s imperfect. I feel like cancer just generally is unpredictable and there are many things that we try as clinicians. And especially with the experience that we have, to say, “This is what we anticipate the course will be like you, in terms of response, in terms of the cancer being quiet.” As you all know, multiple myeloma is not a curable cancer right now. And for all patients, when they’re diagnosed, they’re often able to get disease control and be able for that cancer to be put in remission. And we do focus on remission. 

I think that’s also something that I talk to my patients about. Even though we can’t cure it, we can certainly control it, and that’s a big part of what we do. So, when we get good disease control, we’ll talk more about next therapies, but that is how Dr. Cottini – Dr. Cottini is a wonderful scientific investigator and knows all of the latest and greatest when it comes to different mutations that are identified within cancer cells. We partner very closely with her in terms of  scientific investigation and how the mutations that were newly identified, too, play a role in terms of response to treatment, and how we’re able to best treat them.  

Katherine:

Thank you for that. Dr. Cottini, do you have anything to add as far as what type of questions patients should ask their healthcare team about test results?  

Dr. Cottini:

I mean, I think Dr. Rosko already pointed out the most important things. So, multiple myeloma is a rare disease, and it’s not as intuitive to understand as breast cancer, lung cancer, prostate cancer. 

So, it’s really important as a patient to understand which tests are we ordering. Why are we ordering? How do we monitor the disease? Because that’s one of the most important questions the patient asks, because for different types of solid tumor, we get imaging, and we know that the tumor is growing or not. Where, for us, we look at the markers I had described previously. And sometimes, we maybe see small changes in the markers that are very concerning and worrisome for the patient, but sometimes they are not. So, I think asking questions about the testing and how we treat them and monitor the disease is a very important part of being a good applique for itself. 

Katherine:

Thank you. Dr. Rosko, I’d like to move on to treatment. We know that multiple myeloma patients have a number of options and that many available therapies are used in combination. 

So, I’d like you to walk us through the options that are available. 

Dr. Rosko:

So, I’m going to start by how the best way that I can frame out when we talk about newly diagnosed versus patients when they have relapse. So, there are therapies that are available for patients that are FDA-approved when they are newly diagnosed with the cancer, and there are therapies that are approved only when a cancer has acted up again or relapsed. 

So, I’ll kind of frame it from patients who are newly diagnosed. And then, I also will talk more about relapsed therapies and what we’re able to offer to patients. So, in first, when we talk about treatment options, we frame treatment based on a couple things. So, one is, we talk extensively about the disease biology. So, that plays an important role in how we decide which treatment the patient should get.  

And then, the second part about how – I would probably say there’s about four main parts. And so, disease biology is one, and another thing has to do with the patient characteristics. In terms of the patient’s overall health prior to developing cancer, and also how the cancer has impacted their health in terms of everyday activities. Whether or not a person has really slowed down quickly, whether they’ve been in the hospital, and how it’s impacting their organs. Because that plays a role in terms of what we’re able to give patients.  

If a patient has advanced kidney failure, which can sometimes happen, or if you have to focus more on protecting their bones and if there’s concern about fractures and things like that. And then independent of patient characteristics in terms of overall health, the last part I talk to patients about is their own preferences. It’s a hard thing to talk about, shared decision-making in a cancer that most people have never heard about, but there is certainly – when we talk about options and there are, it’s important to talk about shared decision-making in terms of what’s most important to them and where they – and most patients will say, “Well, I just want the best medicine.” 

And I say to them, “Well, you know, we have lots of options, and that’s the best thing about it, but we also want to be cognizant of the real world, of giving best options,” and for example, Many of my patients – so, I’m at The Ohio State University, I’m here. And a lot of patients travel. I have a lot of older patients that I care for, and they’re very independent with travel. And I want to make sure that whatever therapies we’re getting for them, that we can do this in such a way that maintains their lifestyle.  

So, the beginning part of a treatment, it is broadly described as – when we talk about someone who was diagnosed with this, it’s this thing called induction. So, induction is when we give anywhere from two to four medications to be able to control their cancer and put it into remission. And we know that the cancer is in remission because, like we started out the conversation with Dr. Cottini, myeloma makes proteins. Oftentimes, it makes proteins, those proteins are not nutrition proteins but are cancer proteins that we can track in the blood. 

So, we can check them every month and to make sure that the patients are having a really good response, and as such, we’re able to define that they’re responding to their treatment. Because they have a beginning stage in induction, which they’re given treatment, and then the goal is to put patients put in remission. 

Depending on the overall health of the patient, a standard of care for most patients diagnosed with multiple myeloma is to undergo an autologous stem cell transplant. An autologous stem cell transplant is not a transplant in which you’re getting cells from your brother or sister and they’re being donated to you. They are your own stem cells. We get them out of you when your bone marrow is free of disease, and then we would admit you to the hospital for a more intensive therapy and give them back.  

That is often the standard of care for patients newly diagnosed with multiple myeloma and it is recommended for most patients. Some patients get – I like to think of it as a stem cell transplant not at the time of their initial diagnosis, but later on at the time of relapse or some patients are not candidates for a transplant or elect not to have a transplant. And all of these options are very personalized to the patient. It’s very hard to say that this is exactly what we do. 

Because it’s a strategy where it requires a lot of shared decision-making to make sure that we’re getting good disease control, good quality of life, and deep, deep remissions for our patients. So, then, if a patient gets a transplant, there’s a period of recovery, and then patients go on a pill most often, a maintenance pill that they stay on for indefinitely. 

Myeloma is also a cancer which has perpetual therapy. Very different than many other cancers, where there’s a beginning and an end, myeloma for the most part is perpetual therapy, where you get some form of therapy at higher dosages versus lower dosages over a period of time.  

So, I’m going to talk broadly about the classes of drugs that we have and how we use them to be able to define therapy. 

So, the first class of drugs are called proteasome inhibitors. Just like many other cancers, we use different types of drugs to be able to target different aspects of a cancer cell’s growth cycle.  

So, very similar to how we do other drugs, these are very specific to the cancer cell, and they’re very targeted. So, unlike some of our other kind of classic chemotherapies, many of these medicines that I’m going to talk about are very targeted at the cancer cells without causing too many other problems. 

So, proteasome inhibitors include drugs like bortezomib (Velcade), which is given as a shot, carfilzomib (Kyprolis), which is given as an IV, or ixazomib (Ninlaro), which is given as a pill. They have different indications, but they’re the same class of drugs.  

The next class of drugs is called immunomodulatory drugs, or iMiDs. This includes things like lenalidomide (Revlimid), pomalidomide (Pomalyst). Those are the most common, and then we sometimes use the drug that the original iMiD drug, which is called thalidomide (Contergan). 

These are all pills that patients take, and so that’s oftentimes very nice for patients to be able to provide therapy at home, very well-tolerated. The next class of drugs are called monoclonal antibodies. On a cancerous cell, there is a marker. 

And so, we use monoclonal antibodies to be able to target the marker on the cancer cell. What that means is very specific. To that cancer cell, so, the most common target is the CD38, that’s a marker on one of the cancer cells. And we use a drug called daratumumab (Darzalex), that can be given as an IV or a subcutaneous agent, or another drug called isatuximab (Sarclisa). We also have other markers on the plasma cell. There’s a marker called SLAMF7, which we have other drugs called elotuzumab (Empliciti), which is often used for patients more in the relapse setting.  

Katherine:

Dr. Cottini, I’m wondering if you could briefly go over CAR T-cell therapy and bispecific antibodies. 

Dr. Cottini:

Yes, of course. So, these are all our new therapeutic approaches for patients. And these are types of treatments that are given to patients that already went through their induction, they went into remission, maybe they had a bone marrow transplant. And then, after a couple of years or months, unfortunately the disease came back, and they need the new and different treatment options. So, these two strategies, CAR T and bispecific antibodies, really rely on the T-cells, on the immune cells of the patient.  

And they all focus and target a specific marker on the plasma cells, but they work a little bit differently. So, the bispecific antibodies – and we have different antibodies.  

Some are approved by the FDA, some are just in clinical trials trials. They practically recognize something that is on the plasma cells, on the myeloma cells, that can be BCMA, GPRC5D, or other targets. So, at the same time that I am able to get close by the T cells, the immune cells, and in this way, practically there is both the antibodies and also the immune cells which is activating and getting rid of the cancer cells. 

So, these are infusions. Often, they’re done initially in the hospital and then in the outpatient setting. Sometimes it’s even every week, every other week or so.  

CAR T are different strategies, and it’s a very smart way of trying to get rid of the cancer cells. So, practically, these are T cells.  

So, these are immune cells from you, from the patient. And they are practically taken and then brought to a very specific and clean facilities where these T cells are modified in order to be able to recognize the cancer cells.  

And then these cancer cells are sent back to us and then practically they are given into the veins to patient, and then there is this kind of reaction of these T cells, which are very peppy and aggressive to be able to kill all the remaining cancer cells. So, these are all the new strategies. 

Obviously, we are kind of like in the early process, but these are very promising therapies I think we’ll be maybe moved up front even with diagnosis in the next 10, 20 years, we don’t know. 

Katherine:

I want to thank you both so much for your thoughtful responses. And as we close out the program, I’d like to get a final comment from each of you. What are you excited about in myeloma research, and why should patients be hopeful? Dr. Cottini?  

Dr. Cottini:

So, I think that especially if we look back especially at where myeloma was 20 or 30 years, I think we have made so many progresses, and there is really hope for our patients. I’m very passionate about research. That’s what I do. That’s why I read paper, I publish paper, and I think that it’s the heterogeneity of our disease is huge, and it’s difficult to tackle. But we as researchers, as physicians are the ones that can look at these changes, and find new therapies for our patients. So, I think that research is the way to go to be able to finally cure our patients. 

Katherine:

Dr. Rosko? 

Dr. Rosko:

Yeah, I mean I go Dr. Cottini’s sentiments. The multiplying therapies for myeloma really provides our ability to prescribe and make myeloma more of a chronic illness for our patients. I think it’s really important to allow patients to get really good targeted therapy personalized to them. Of course, we all are looking forward here to deep remissions. We want to be able to do that in such a way where we have good quality life for our patients. 

I think, importantly, as part of this program does here, we have to create access. So, most of myeloma is treated in the community, and most myeloma is diagnosed in older adults. And I really think how important it is, we talk about clinical trials, and being able to get our patients on to clinical trials, and to be able to get more knowledge about the disease process of pathogenesis, which I think is just really pivotal. 

So, I’m excited about personalizing therapy to the individual’s health and really being able to increase access to all of these novel therapies that we have. For patients, often at specialized cancer centers, but I’m really interested in how we can increase reach and access for all of these advances in myeloma research to every patient no matter where they’re at. 

Katherine:

Well, thank you both for joining us today. And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for being with us.  

Myeloma Combination Therapy | What Patients Should Know

Myeloma Combination Therapy | What Patients Should Know from Patient Empowerment Network on Vimeo.

Expert Dr. Jeffrey Matous shares an overview of myeloma treatment classes, why combination therapy can be effective, and the importance of clinical trials in patient care and moving research forward.

Dr. Jeffrey Matous is a myeloma specialist at the Colorado Blood Cancer Institute and the assistant chair in myeloma research for Sarah Cannon Research Institute. Learn more about Dr. Matous.

See More from Evolve Myeloma

Related Resources:

Questions and Considerations When Making Myeloma Treatment Decisions

Should You Push for a Stronger Myeloma Treatment at Relapse

Transcript:

Katherine:

There are several treatment classes for myeloma, such as immunomodulatory therapy and proteasome inhibitors, for example, and they’re often used together. So, what is a combination therapy and why is it used so frequently for myeloma?  

Dr. Jeffrey Matous:

Absolutely, so with learned over the years in myeloma that combining different types of drugs that work in different ways, we call those classes, so different classes of drugs, combining them together is the optimal treatment for myeloma.  

And back in the day, we used to use two drugs. Then, we learned that three drugs are better than two drugs, and now, we have data that four drugs are better than three drugs. And so, we bring in drugs from all kinds of different categories for our patients. And we even know that for the non-transplant-eligible patients, for the older patients, for example, that combining drugs from different classes is really, really important to get the best outcomes. And in general, the three classes that we use – the four classes that we use when we’re treating myeloma patients initially include the immunomodulatory drugs, and examples of those are lenalidomide, also called Revlimid. pomalidomide, also called Pomalyst. Thalidomide’s (Thalomid) an older drug, but we still occasionally use it.  

And then, we have the proteasome inhibitors. Examples of those are bortezomib (Velcade), carfilzomib (Kyprolis), and to a much lesser extent, there’s one called ixazomib (Ninlaro). And these days, we know that CD38 antibodies are really important and really getting their foothold into the initial treatment of myeloma.  

Examples of CD38 antibodies are daratumumab (Darzalex) or isatuximab. And then, usually, we combine these treatments with steroid medicines to sort of increase the effectiveness of the regimens. That’s how – those are the classes that we use when we’re treating myeloma. 

Katherine:

Okay and have you learned about adding one treatment to another to another through clinical trials or is trial and error? 

Dr. Jeffrey Matous:

Absolutely. We would not be where we are right now without the conduct of clinical trials. I always tell my patients by the time something’s approved in myeloma, and we had things approved in 2022, the field is already moving past that in clinical trials. It’s unbelievable. So, I’ll give you an example. When daratumumab, one of these antibodies, got approved by the FDA, already when it got approved by the FDA, we knew through clinical trials that were being conducted that combining it with other types of medicines was far more potent. 

And we have countless examples of this, so yeah. Absolutely, so every treatment that we use in myeloma, we discovered and developed through a clinical trial. And I always encourage my patients strongly to consider clinical trials, and then, we have to explain, because when patients hear clinical trials, and I could be deviating a little bit here, Katherine.  

They often think about experimentation and testing things that are unproven. In myeloma, we occasionally do that, but far and away, the overwhelming majority of our clinical trials are testing agents that we know are effective. We’re just trying to figure out what the best combination is and make sure that it’s safe for patients. 

What Should You Know About Emerging Myeloma Treatment Options? Resource Guide

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See More from Evolve Myeloma

What Should You Know About Emerging Myeloma Treatment Options?

What Should You Know About Emerging Myeloma Treatment Options? from Patient Empowerment Network on Vimeo.

With myeloma treatment and research advancing quickly, it’s important to stay up-to-date on the latest therapies. Myeloma expert Dr. Jeffrey Matous reviews new and emerging myeloma treatment approaches, how these therapies work, as well as the potential risks and benefits of each option. Dr. Matous also shares resources for learning about myeloma and how to access better care.

Dr. Jeffrey Matous is a myeloma specialist at the Colorado Blood Cancer Institute and the assistant chair in myeloma research for Sarah Cannon Research Institute. Learn more about Dr. Matous.

Download Resource Guide

See More from Evolve Myeloma

Related Resources:

What Are the Phases of Myeloma Treatment

What Is CAR T-Cell Therapy for Myeloma?

Tools for Choosing Myeloma Therapy

Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is about advances in myeloma treatment and how emerging therapies may affect your care decisions.  

Before we get into discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining me is Dr. Jeffrey Matous. Dr. Matous, welcome. Would you please introduce yourself? 

Dr. Matous:

Thank you very much, Katherine. I’m Dr. Jeff Matous, and I am physician at the Colorado Blood Cancer Institute, and also, the Assistant Chair in Myeloma Research for Sarah Cannon Research Institute here in Colorado. 

Katherine:

Thank you so much for taking the time to join us today. 

Dr. Matous:

It’s a pleasure. 

Katherine:

Before we get into our discussion, would you share with the audience how the field of myeloma has changed over the course of your career? 

Dr. Matous:

It’s unbelievable. I mean, I started treating myeloma back in the days of VAD, vincristine (Oncovin), doxorubicin (Adriamycin), dexamethasone (Decadron) 96-hour pumps with 40 pounds of dexamethasone that we put into patients, and wow. We didn’t have much else. We didn’t know how long to treat people, and then, in the 2000s, we have the revolution of all the new therapies, and it just keeps going and going and going. It really is an exciting to be in this field. 

Katherine:

Yeah. Let’s begin by sharing some advice for navigating myeloma care on a basic level. First, what testing should take place following a myeloma diagnosis? 

Dr. Matous:

Well, I think even before that, Katherine, I always tell my patients that an educated patient, like the people that are on this webinar, are the best patients, and so, when I meet a patient for the first time, we spend a lot of time educating patients even before we delve into a lot of the testing. 

And I refer them to excellent resources out there. Examples of these are the International Myeloma Foundation, or the Multiple Myeloma Research Foundation.  

There are others, of course, and so I really encourage my patients. In fact, I usually show them how to navigate these sites. And then, we get into testing, and testing in myeloma is multifaceted, because myeloma can affect patients in so many different ways. For example, it involves radiology studies to look for bone disease, urine work to see if the kidneys are affected by myeloma, a lot of blood work, and then, we also do a lot of testing to make sure that we understand the whole health of the patient, because that comes into play so much when we’re making treatment decisions in myeloma. 

Katherine:

Yeah. What factors impact treatment decisions? 

Dr. Matous:

Well, there are so many. One of the key ones is fitness, and fitness is a term that myeloma doctors use and rely on tremendously. 

And fitness, more or less, falls into a couple different categories. It’s more complex than that, obviously, but generally speaking, it’s too old or too frail, or young and vigorous and I stress to my patients that vigorous or frail is not determined by chronological age. It’s determined by your physiologic age. That’s really critical, so determining what your patient’s overall fitness is, is really important in myeloma. And then, we have to assess the risk of myeloma. I think we’ll talk about this a little bit later, because not all myeloma is the same and we treat myelomas differently depending on risk, certainly. And then, patient preference is a huge part, because there are so many ways to treat myeloma these days that we explore options with the patients and sometimes patients have pretty strong opinions about, you know, one type of treatment or the other, for example. 

Katherine:

What advice do you have for patients and caregivers related to working with their healthcare team in choosing a therapy? 

Dr. Matous:

Yeah. I think the big thing is to do some research on your own, but really, ask questions when you see your physician. I mean, ask questions about, for example, what are my treatment options? Are there clinical trials that might be available to me? What’s on the cutting edge in myeloma? What are the standard therapies? What are the pros and cons? And a question I often counsel patients to ask when they’re seeking other opinions is if you had 100 people like me and you treated them this way, how many would do well and how many would not do so well, and prognosis, and so forth. And then, the other thing I think is really important sometimes is gauging how experienced your physician is in treating myeloma, because we actually have data that shows that patients who are treated in myeloma centers actually fair a little better than those who are not. 

Involving a myeloma expert in your care doesn’t necessarily mean you have to get your care at that center. It just means you may want a myeloma expert on your team. Pretty much every doctor I know welcomes a myeloma person on their team, because the field is so rapidly evolving. It’s really hard to keep up with for a lot of people. 

Katherine:

Yeah. That’s great advice, Dr. Matous. Thank you. Stem cell transplant is often considered for myeloma patients. Can you talk about who this treatment option might be appropriate for? 

Dr. Matous:

Absolutely, so we’ve known for decades that, what I call high-dose chemotherapy, also called stem cell transplant, is a very effective and very potent treatment of myeloma and we’ve shown that time and time again in clinical trials, including some recent ones that are published just in 2022.  

And so, high-dose chemotherapy and stem cell transplant is not for everyone. You have to be fit enough to undergo it, and this is not age determined. It’s fitness determined. And then, a lot of people live a long way from centers that perform high-dose chemotherapy and stem cell transplants. 

If patients have to travel hundreds of miles, then sometimes that comes into play. Hey, I just can’t do this. I can’t get the time off, and uproot, and bring a caregiver, and travel 300 miles to get this care, so sometimes that comes into play. Physician bias definitely comes into play. We know that some physicians are stronger proponents of high-dose chemotherapy and stem cell transplant, and I fall into that category, but we have other physicians that may not even bring it up as an option to their patients. We know, for example, that African Americans and other minorities are notoriously under-referred for high-dose chemotherapy and stem cell transplant. A lot of decisions go into that, and again, this is one of those situations where if you’re transplant-eligible, that means you’re young and vigorous, and on paper, a candidate. You want to go, at the very minimum, consult with physicians that do high-dose chemotherapy and stem cell transplant and hear about that option. 

Katherine:

Yeah. You mentioned high-risk myeloma earlier. How do you determine if a patient is high risk or low risk? 

Dr. Matous:

Absolutely, so this is not uniformly agreed upon among myeloma doctors, but in general, we assess risk based on a few different things. One is called staging, and we stage myeloma unlike any other cancer, so it’s not staged like breast cancer, or lung cancer, or prostate cancer. It’s staged according to something called R-ISS, RISS, and you get, basically, a one, two, or a three.  

Those are your stages, and in general, if your stage three, you have higher risk disease, but even more than that, we’re beginning to understand how myeloma cells misbehave at the genetic level, and we know that there are certain genetic findings inside the myeloma cell that can convey higher risk features. It’s important to stress to patients that these are not genetic findings that they were born with or can pass on through hereditary. 

These are findings that occurred during the life of the patient that occurred by chance and developed inside that cell that turned into myeloma, and those are the genetic changes that we’re talking about. And we know that certain of these genetic changes confer higher risk disease. And in general, Katherine, if I see 100 people with myeloma, about 85 of the 100 will fall into what I call a standard risk category and about 15 percent will fall into what we call the high-risk category. 

Katherine:

Okay. That’s really good to know. Thank you. There are several treatment classes for myeloma, such as immunomodulatory therapy and proteasome inhibitors, for example. And they’re often used together.  

So, what is a combination therapy and why is it used so frequently for myeloma?  

Dr. Matous:

Absolutely, so with learned over the years in myeloma that combining different types of drugs that work in different ways, we call those classes, so different classes of drugs, combining them together is the optimal treatment for myeloma. 

And back in the day, we used to use two drugs. Then, we learned that three drugs are better than two drugs, and now, we have data that four drugs are better than three drugs. And so, we bring in drugs from all kinds of different categories for our patients. And we even know that for the non-transplant-eligible patients, for the older patients, for example, that combining drugs from different classes is really, really important to get the best outcomes. And in general, the three classes that we use – the four classes that we use when we’re treating myeloma patients initially include the immunomodulatory drugs, and examples of those are lenalidomide, also called Revlimid. pomalidomide, also called Pomalyst.  

Thalidomide’s (Thalomid) an older drug, but we still occasionally use it.  

And then, we have the proteasome inhibitors. Examples of those are bortezomib (Velcade), carfilzomib (Kyprolis), and to a much lesser extent, there’s one called ixazomib (Ninlaro). And these days, we know that CD38 antibodies are really important and really getting their foothold into the initial treatment of myeloma.  

Examples of CD38 antibodies are daratumumab (Darzalex) or isatuximab. And then, usually, we combine these treatments with steroid medicines to sort of increase the effectiveness of the regiments. That’s how – those are the classes that we use when we’re treating myeloma. 

Katherine:

Okay and have you learned about adding one treatment to another to another through clinical trials or is trial and error? 

Dr. Matous:

Absolutely. We would not be where we are right now without the conduct of clinical trials. I always tell my patients by the time something’s approved in myeloma, and we had things approved in 2022, the field is already moving past that in clinical trials. It’s unbelievable. So, I’ll give you an example. When daratumumab, one of these antibodies, got approved by the FDA, already when it got approved by the FDA, we knew through clinical trials that were being conducted that combining it with other types of medicines was far more potent. 

And we have countless examples of this, so yeah. Absolutely, so every treatment that we use in myeloma, we discovered and developed through a clinical trial. And I always encourage my patients strongly to consider clinical trials, and then, we have to explain, because when patients hear clinical trials, and I could be deviating a little bit here, Katherine.  

They often think about experimentation and testing things that are unproven. In myeloma, we occasionally do that, but far and away, the overwhelming majority of our clinical trials are testing agents that we know are effective. We’re just trying to figure out what the best combination is and make sure that it’s safe for patients. 

Katherine:

Yeah. Dr. Matous, some of our viewers may have already been through some therapy at some level. Let’s dive into new and emerging treatment. CAR T-cell therapy has been approved for myeloma patients and it’s certainly a hot topic right now. Can you tell us about this treatment and who it might be right for? 

Dr. Matous:

Absolutely, so these T-cell therapies in myeloma are really exciting, and basically, how they work is T cells are cells that normally, in our body, they’re part of our immune system. When they see something foreign, usually, it’s a foreign infection or some kind. T cells go into kill mode and take out the foreign invader, and they’re supposed to do this with cells that are thinking about turning into cancer, but for various reasons, cancer cells can escape the T cells, and then, kind of brainwash the new system to say, hey. It’s okay if we coexist with you. No big deal. We’ll just hang out together. Okay? And that’s not okay. And so, in CAR T-cell therapy, what we do is we take the patient’s T cells.  

We remove them from the blood with a procedure called apheresis, which is a machine that many patients might be familiar with through their stem cell collections. 

It’s the same machine. And we collect these T cells. Then, they go to a laboratory where they are genetically modified in the laboratory using very sophisticated techniques to become myeloma killers. And we tell – we educate the T cells to become myeloma killers. We grow them up in sufficient numbers, and then, we return them to the patient. We just, basically, put them back in the patient’s bloodstream in the vein and they go and they are really effective at killing myeloma cells. And that’s CAR T-cell therapy, so it’s an amazing immune therapy. It’s way more complicated than I laid out, of course, but that’s the general thought behind it. 

Katherine:

What are the risks of this therapy? 

Dr. Matous:

Absolutely, so we have a lot of patients who come and ask about CAR T-cell therapy and think that it’s the same thing as getting daratumumab in the clinic or carfilzomib in the clinic.  

Get it and you’re on your way. Far from that, and so, CAR T-cell therapy has a lot of risks. The risks fall into a few different categories. The first risk is called CRS, which doesn’t stand for what you think it stands for. It stands for Cytokine Release Syndrome. This occurs when the T cells recognize the myeloma cell and kill it, and when they do this, a lot of substances get released in the body that can cause a lot of symptoms, like fever, or low blood pressure, or low oxygen, and this requires specialized management to shepherd people through this.  

This almost always occurs in about the first week of the treatment after the patients receive the CAR-T cells. In addition, patients who receive CAR-T cells can have what’s called neurologic toxicity that falls into many different categories. It can be something as simple as a headache, or a transient or temporary difficulty, you know, saying words or being confused, or in the most severe situation, even a seizure. 

This requires a lot of close monitoring for neuro toxicity. In addition, we know that patients that get CAR T-cell therapy are, for quite a while after they receive the CAR-T cells, an increased risk for infection. It’s very suppressing of the immune system, immunosuppressive. And lastly, a lot of our patients who go through CAR T-cell therapy have low blood counts for a long time and they have to be monitored for this, might need transfusions, or some different therapies. It’s a complicated therapy for sure. 

Katherine:

Yeah, so what questions should patients be asking their doctor when considering CAR T-cell therapy? 

Dr. Matous:

I think the first thing, of course, is am I a candidate, because the commercially approved CAR-T cells, there are very specific criteria for who’s a candidate, who could receive it. Okay, and then, you want to know, one, if you’re a candidate. Two, what the risks and benefits are. 

Three, are there alternatives besides CAR T-cell therapy. Is it too early or too late to do this? Should we think about maybe another clinical trial or one of the T-cell redirecting antibodies, for example? You want to ask those questions for sure. These treatments are tremendously expensive, of course, and so that may come into play, as well. You want to know what the experience of the center is with CAR T-cell therapy, I think, and then, you also want to know are there clinical research studies for which you might be eligible to have CAR-T cells, not just commercially available ones, because we have two that are commercially available right now, and we have scores of CAR T-cell treatments that are still in clinical trial. [22:32] 

Katherine:

Yeah. Well, thank you for that, Dr. Matous. 

I know many viewers will appreciate all of this information. Let’s switch gears now to another therapy we’ve been hearing about; bispecific antibodies. One has been recently approved for myeloma, teclistamab, so let’s start with what are bispecific antibodies and who might they be right for? 

Dr. Matous:

And strap on your seatbelt, because there’s a whole bunch of them coming, I think, for approval. So, the T-cell redirecting antibodies, it’s a different strategy for trying to get your T cells, the patient’s T cells, to attack the myeloma cells. And in CAR T-cell therapy, it’s a single infusion. That’s the treatment. And the bispecific antibodies that I often call T-cell redirecting antibodies, because they redirect the T cells to the myeloma cell, these are given over a continuous period and it might as long as you tolerate it, as long as it’s working. It might be for a year. And they are given either under the skin as a subcutaneous injection, or in the vein. 

And there are many, many different of these T-cell redirecting antibodies, the bispecific antibodies. How they work, I just do this with my patients. I hold up my hand and I say the bispecific antibodies have two hooks on them, and one hook recognizes the T cell and latches onto the T cell, and the other hook latches onto the myeloma cell. And then, what it does, it brings the T cell in proximity to the myeloma cell. Then, the T cell says “Oh, aha. I’m supposed to kill this myeloma cell,” and usually does it. Now, the part that connects the T cell and these bispecific antibodies is always the same. It’s CD3. However, the part that sticks on the myeloma cell, there are different targets, and you referred to teclistamab (Tecvayli), which was approved by the FDA, and that attaches to something on the outside of a myeloma cell called BCMA, BCMA. 

But we know that other bispecific antibodies that can attach to different markers or antigens on the outside of the myeloma cell and affect the same change, and so, I think these are going to be coming fast and furious. 

Katherine:

Who’s this class of treatment right for? 

Dr. Matous:

I think – well, again, the FDA approval right now is for people who have seen pretty much everything. You know, you’ve had a lot of treatments. You’ve seen all the different classes of the myeloma drugs, but in our clinical research trials right now, we’re testing these as an initial therapy, in second-line therapy, after stem cell transplants. They’re being tested pretty much in every scenario right now in clinical trials, so right now, it’s when you’ve exhausted the normal treatments and you’re considering CAR T-cell therapy, or you’re considering getting treated with a drug called selinexor (Xpovio), or looking at another clinical trial. That’s when it’s the time to ask about the bispecific antibodies. 

Katherine:

What are the risks and benefits of this therapy?  

Dr. Matous:

The risks are pretty similar to the risks from CAR T-cell therapy, so Cytokine Release Syndrome. That usually occurs during the first week. Neurologic toxicity is, I think, less frequent with the bispecific antibodies, but infections and low blood counts definitely a concern with these bispecific antibodies, requires a lot of monitoring without any doubt.  

Now, the other thing about the bispecific antibodies, there’s, right now, they’ve been in the realm of the larger centers, so myeloma centers is where people have been getting these bispecific antibodies, but there’s absolutely no question in my mind that these bispecific antibodies are going to be available through almost every general hematology, oncology practitioner’s office, but not for a while. The docs that aren’t used to giving these medicines are a little – they’re being quite cautious rolling them out in their practices right now. There are still a lot of questions as these roll out, and so, right now, I think teclistamab is still largely unavailable outside myeloma centers, but that’s going to change, I think, even over 2023 and definitely into 2024. 

Katherine:

Okay. That’s really good news. For patients who want to know more about bispecifics, what questions should they be asking their healthcare team? 

Dr. Matous:

Again, the same thing is – the same questions. Well, teclistamab is approved by the FDA. What other bispecifics are there? What about combinations? What about clinical trials? And then, that’s what you want to ask for sure. Then, how often do I need to come in the office? With teclistamab, the answer is weekly.  

If they say for how long, it’s until it quits working or you have side effects, and then you can’t take it anymore. That’s the way the FDA label is. And so, it’s a big commitment to go on these treatments, but they’re effective. You ask me about the effectiveness of these drugs and, essentially, all the studies with these different bispecifics, including teclistamab, have been studied initially in people who have seen every myeloma treatment. They’ve had an average of about six different myeloma treatments. 

They’ve seen all the drugs. They’re not working anymore. They’re in trouble. They’re in a pinch, and roughly, seven out of ten people have dramatic responses to these bispecifics when they’re treated, which we’ve never had anything like this at all in the myeloma world. 

Katherine:

Wow. Do the side effects go away at some point? 

Dr. Matous:

The side effects are completely manageable. Yeah and you can – by and large, you can adjust the bispecific, either the schedule or different things, to make these completely tolerable for patients. 

Katherine:

Okay. 

Dr. Matous:

Very few patients on our trials, with these bispecifics, who we have not been able to manage and, pretty much, handle all the – any side effect that occurs. 

Katherine:

Okay. That’s good. Are there other emerging myeloma therapies that patients should know about? 

Dr. Matous:

There are a bunch of other therapies. Looking at in myeloma, for sure, and a lot of these other therapies are – they’re exploring the same pathway where the proteasome inhibitors work, but in a little different way. 

And proteasome inhibitors, again, just to refresh your memory, are  Velcade or bortezomib, Kyprolis or carfilzomib, and there are different drugs that work in this area that are being explored. And also, for the immunomodulatory drugs, there are different what are called cell mod or cell-modifying drugs that are being developed. Also, at our recent hematology meeting last December where all the blood doctors get together, there was a lot of research presented looking at using different cells for attacking the myeloma, for bringing back an old friend, interferon, to fight the myeloma through a new sophisticated way. The field is just really going at breakneck speed right now. 

Katherine:

Where do clinical trials fit into myeloma care? 

Dr. Matous:

I’m biased, Katherine. I think in every step of your myeloma journey you should ask about a clinical trial, because clinical trials might be appropriate as initial therapy, second-line therapy, third-line therapy, post-transplant maintenance therapy. There are clinical trials available, pretty much, at every phase of myeloma care, and so, I think it’s important that you here about your clinical trial options when you’re talking with your physician. Now, for some folks, it’s going to be hard to get on a clinical trial. You might be a long way from a center that does very many clinical trials, but you should always, always ask about it and there are many resources for researching clinical trials that are out there, right? One example is you can call The Leukemia & Lymphoma Society and they have counselors on the phone that can guide you toward clinical trials. You can go to clinicaltrials.gov. You’re paying for it. Might as well use it and search clinical trials there. It’s a pretty easy site to use, as well. 

My answer is at every phase of your journey, whenever you’re considering a treatment or a new treatment for myeloma, you want to know what your clinical trial options are. 

Katherine:

How can patients and care partners stay informed about the latest myeloma research? You mentioned a couple of websites. Are there others? 

Dr. Matous:

There are. There are a bunch of these that are out there, right? There’s the Myeloma Crowd. There’s – you know, this webinar. The Leukemia & Lymphoma Society in the Rocky Mountain area, we have, every year, a blood cancer conference that we put on free for patients through The Leukemia & Lymphoma Society that reviews new goings on in the field of myeloma, so there’s a lot of information out there and just a little bit of effort on the web. You can find great resources. Again, the ones I mentioned earlier I think are my top ones. Particularly, the IMF, the International Myeloma Foundation, because the physicians who run that and the people who run that, they made sure that everything that’s on there is entirely believable. 

Katherine:

Yeah. Okay. Let’s get to a few audience questions that we received before the webinar. Kendall writes, “I’m in the maintenance stage following initial diagnosis and treatment. At first relapse, is it appropriate to push for stronger treatment in hopes of a cure?” 

Dr. Matous:

Yeah, so the answer to that has changed. The answer is yes, and so, the – it used to be said in myeloma that your best treatment was your first treatment. Then, if you relapsed, that the treatments didn’t work as well, and the remissions did not last as long. Throw it out, so now, we get multiple chances to get really deep remissions in patients, and we should be every bit as greedy when we’re treating relapsed disease, at least initially, as we are when we treat disease at the very beginning. We know, for example, that there are many second-line therapies. I’ll just throw out some examples – daratumumab, pomalidomide dex, daratumumab Revlimid dex, daratumumab Velcade dex.  

Not to mention, the T-cell therapies that can put patients in remissions that are so deep that we can’t even find myeloma cells using very sophisticated molecular techniques, so be greedy. 

Katherine:

Yeah. Okay. Good advice. PEN community member, Greg, sent in this question. “Can you discuss any future or potential changes to using stem cell transplant for myeloma patients?” How would you counsel patients who do not want to pursue a transplant as a treatment option? 

Dr. Matous:

So, for stem cell transplant in myeloma, for years, it’s been the standard of care for suitable patients. And every couple years, I liken this to that game we used to play called King of the Hill growing up where stem cell transplants, King of the Hill, and everyone tries to knock stem cell transplant off the hill. And so far, it really hasn’t happened. And so, transplants still, I think, an important part of the overall care for suitable patients. 

For patients who are eligible and safe enough to undergo transplant. However, not all – now, will this be challenged in the future? And the answer is – I think the next challenger, and this will be a serious challenger, will be CAR T-cell therapy. And so, we have to figure out if CAR T-cell therapy or the bispecific antibodies are safe enough to give at the beginning and as effective as stem cell transplant and what the long-term side effects, how they might differ, as well, so that question is going to be tackled in the myeloma word, but it’s going to be several years until we have an answer there, for sure.  

So, for my patients who are otherwise candidates for stem cell transplant, but who don’t want to do it, usually, I’ll say, “You may change your mind in the future. In myeloma, it’s important to keep all your options open and you should at least discuss with the transplant center collecting and freezing away your stem cells for a rainy day to keep that option open to you.” So, even you’re thinking of not doing it, it might be a good idea, it probably is a good idea, to harvest and store your stem cells at a transplant center. 

And then, if you’re not going to do transplant up front, they key is to stay on prolonged maintenance therapy.  

We know that that’s one of the keys for making survival as long as possible in patients who don’t do a transplant is to continue on ongoing maintenance therapy as long as possible. Don’t curtail your therapy just because you’re not doing a transplant. 

Katherine:

Right. Okay. Well, thanks for that, Dr. Matous.  

Those were all great questions. Please continue to send them in to questtion@powerfulpatients.org and we’ll work to get them answered on future programs.  

So, Dr. Matous, as we close out the program, we’ve definitely learned that the field of myeloma is advancing very quickly. Would you share with us why you’re hopeful? 

Dr. Matous:

Yeah. It’s because for – I’ve been doing this quite a while and I always used to tell my patients if you just hang around. 

If you stay in the game, something else is going to come that we don’t even know what it is right now that’s going to impact your life, your quality of your life, the longevity of your life, and be a good treatment for you. And so far, that’s been the case. And right now, with the T-cell therapies, I’m really, really excited about how they can impact the cure of our patients. I also think that the basic research that’s going on in myeloma right now, and this is done by the real smart scientists, not the clinicians like me, but the really smart people that work in the laboratory. Learning how myeloma cells misbehave at very amazing levels, and when we learn that, it almost always results in a treatment that benefits our patients.  

And so, I think that we have every reason to be optimistic for our patients with myeloma, because of all the treatments that are coming out that we know about, that we know are around the corner, and for those that we don’t even have an idea what they are yet. 

Katherine:

Yeah. Well, it seems like there’s a lot to be hopeful about in myeloma care. Dr. Matous, thank you so much for joining us today. It’s been a pleasure. 

Dr. Matous:

Well, the pleasure’s been mine. I love talking to myeloma patients and I would just encourage you to keep getting all the information you can. The field’s moving really fast. Just keep up with it and don’t lose hope. 

Katherine:

Yeah. And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.  

Is There Financial Assistance for Myeloma Patients?

Is There Financial Assistance for Myeloma Patients? from Patient Empowerment Network on Vimeo.

Can myeloma patients access financial assistance for their care? Expert Dr. Benjamin Derman shares information about available support and resources to reduce the financial burden on patients.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

See More from Engaging in Myeloma Treatment Decisions

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Transcript:

Katherine:

One final question for you. Jennifer asks, “Many new medications for treatment were mentioned. And I’m sure these could be expensive. What are the options to make these available financially for patients who need them?”  

Dr. Derman:

That’s a really good question, and one that we don’t yet have great answers to. As a physician, I don’t receive compensation based on the drugs that I prescribe. And so, I do know – I often have a good sense of what these drugs cost. A lot of the costs that are passed along to patients typically revolve around oral therapies. Even patients who are on Medicare, or sometimes especially patients who are on Medicare. And looking at some of the policy changes that seem to be coming down the pike that include capping Medicare out of pocket costs for medications will be a huge benefit to our myeloma patients.  

It’s important to familiarize yourself with different organizations and the financial support that may be available. Just to name a few, and you’re not limited to these, but The Leukemia & Lymphoma Society does a really great job in providing financial support to patients. But there are definitely other programs that can be contacted for this.  

And also, a lot of the pharmaceutical companies will actually have patient assistance programs as well. Sometimes it’s as simple as asking your provider, and typically they will have their team look into this for you. But we’re fortunate to have a team of pharmacists and my nurses as well who are used to doing this kind of thing. So, it’s important to look into those as well.

How Can Myeloma Patients Cope With Fatigue?

How Can Myeloma Patients Cope With Fatigue? from Patient Empowerment Network on Vimeo.

Fatigue can have a big impact on daily life for people with myeloma, so how can this common symptom be managed? Expert Dr. Benjamin Derman shares insights about why fatigue occurs, advice about treatment timing, and recommended adjustments to optimize energy levels.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

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Transcript:

Katherine:

Craig sent in this question prior to the program. “My primary side effect is fatigue.” And you just mentioned that. “What advice do you have for planning activities through the day?”  

Dr. Derman:

So, this is a very common side effect that we see. In part, it can be from the disease itself. And if that’s the case, it’s going to get better as treatment works. In other cases, it’s due to the treatment itself. And sometimes there are controllable aspects. If it’s a pill, let’s say, where you can control the timing of when you take it. I often tell patients, “Take the drug at night. Because if it makes you tired, at least you’re going to be going to sleep at that point.” 

I do think making sure that you have a good night’s sleep is important. I think making sure that you keep your day-night cycles. So, even if you feel fatigued and you’re at home, it’s not good to be having the windows closed and not being exposed to the outdoors at all. You need light during the day. That’s a normal human need. We do the same thing when patients are in the hospital, and it’s very easy to get your day and night cycles messed up.  

And the other thing too is planning periods of the day when you know that your activity level is going to be, or your energy level is going to be higher, and planning your activities around those times. I think those are at least some important things that we can do.  

Myeloma Maintenance Therapy | What Patients Need to Know

Myeloma Maintenance Therapy | What Patients Need to Know from Patient Empowerment Network on Vimeo.

What should myeloma patients know about maintenance therapy? Expert Dr. Benjamin Derman discusses the role of maintenance therapy, data presented at the 2022 American Society of Hematology (ASH) meeting, and the role of minimal residual disease (MRD) testing in myeloma care.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

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Transcript:

Katherine:

When a patient goes into remission, they’re often placed on a maintenance therapy. What’s the role of maintenance therapy in myeloma care?  

Dr. Derman:

Yeah. So, maintenance, just to specify, is typically something that we call a long duration of usually, less intensive therapy after a more intensive schedule of therapy. So, the most common area that we talk about maintenance is after, let’s say, an autologous stem cell transplant, which came after induction therapy that I mentioned.  

But for patients even who don’t go to a stem cell transplant, they can also go on maintenance therapy. So, when we think about the frontline setting, which in this case would be induction transplant maintenance, the most commonly used drug is a single agent lenalidomide (Revlimid). And that’s been shown to have survival benefits not just in keeping the disease away, but also helping patients live longer. So, maintenance therapy does seem to carry some real importance. One of the things though that we don’t know, is really how long patients need to be on maintenance therapy.  

So, we can all accept I think in the myeloma field, if there’s one thing we can agree on, is that maintenance is important. But the question is, what makes up that maintenance therapy? And then how long? Those are questions we don’t really have the best answers to. And actually, one of the areas that I do quite a bit of research in is about this, how long do patients need to be on therapy?  

So, we recently published some – we presented at ASH this year in 2022, some recent data, at least a preliminary data on patients who had really deep responses, and who we stopped their maintenance therapy after at least one year – but the average was about three-and-a-half years on maintenance therapy – to see if the disease would actually be at risk of coming back.  

And so, what we’re finding is that even in the first year, about 85 percent of patients did not have their disease come back after stopping therapy. So, maintenance therapy is certainly important, but I think we still have to figure out how long patients need to be on that therapy.  

Katherine:

Right. And I can imagine that each person, each patient is different, and some – the maintenance therapy would work really well for them for a long period of time. For others, not necessarily.  

Dr. Derman:

Yeah. I mean, a lot of it comes down to the risk there of the patient’s myeloma. And what I mean by that is – so, somebody has explained to me previously, and I really like the analogy that myelomas are kind of like people. They have different personalities, and they give first impressions. And sometimes your first impression of a myeloma may end up being wrong. You thought it was going to be really hard to treat and you found out that it actually responded pretty nicely to therapy. And other times, it’s the other way around.  

But for the ones that give us a bad first impression, we’re going to be treating those patients typically more aggressively. At least that’s my personal approach. And I take that all the way through from induction, to transplant, even into maintenance therapy where I mentioned already, most people will prescribe a single drug as maintenance therapy. But for those patients, I’m typically going to be prescribing more than that. Or I will continue more aggressive therapy for longer. So, that’s where you have to sort of adapt your therapy in some cases to the patient and their disease characteristics.  

Katherine:

Related to maintenance therapy, we received this question before the program. How do doctors feel about maintenance breaks if you are MRD-negative? Or in a very good response?  

Dr. Derman:

So, I want to be very careful about how I respond to this. Because what I’m going to say is, there’s currently no data to tell us that patients should stop. I mean, in part that’s, you should stop therapy. In part that’s what I’m hoping that we can answer with our study. There’s another large cooperative group study trying to answer this as well, about the duration piece and whether people can stop.  

So, a very good partial response signifies at least a 90 percent reduction in the tumor, in the myeloma, but not 100 percent.  

And there’s also a complete response, which means there’s no detectable disease by conventional methods in the bone marrow or in the blood, but that there can still be microscopic or low levels of cancer cells which we call minimal residual or measurable residual disease. Also called MRD.  

So, MRD negativity is a not so nascent field now, where we are trying to quantify small amounts of cancer cells that may still be present. And the theory is that the presence of residual disease at a small measurable level is what’s ultimately responsible for myeloma relapsing.  

We used to think like, “Oh, a patient is in a complete response. That’s amazing. Let’s clink our champagne glasses. Let’s celebrate.” And there’s still cause for celebration for that. That is a great achievement. But we know that that doesn’t mean we can rest on our laurels. If there is MRD-positive disease, then the disease, it can likely come back. And that’s where suppression of the disease with something like maintenance therapy with lenalidomide is probably helping a lot.  

Katherine:

Yeah. 

Dr. Derman:

But let’s say we have people who don’t have detectable disease, the question is, can they stop? And like I mentioned, we’re trying to answer that question. I would say right now, there’s no recommendation for that. I can’t say in good faith that you should be doing that, unless it’s as part of a clinical trial, which is what we’re hoping to answer.  

What Is Known About the Risk of Myeloma Relapse?

What Is Known About the Risk of Myeloma Relapse? from Patient Empowerment Network on Vimeo.

Myeloma relapse is common, but what is known about the the probability of relapse? Expert Dr. Benjamin Dermain explains the significance of clinical trial data and the important role of blood work, including monitoring M-spike and light chain levels.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

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Transcript:

Katherine:  

Is research being done to determine the likelihood of relapse and when that might occur?   

Dr. Derman:  

Yeah. I mean, we can look at clinical trial data for regimens that have been tested in the relapsed or refractory setting and say, “Okay, we know that this three drug regimen typically gives patients a year before the disease comes back.” Or “This one gives two-and-a-half years or three years.” So, that’s one piece.  

But when you think about who – if you wanted to know ahead of time, “Okay, a patient with high-risk disease, they’re likely not to have as good of a response.” But nobody knows ahead of time the exact amount that they’re going to relapse.  

But one of the things that we focus on, part of the reason that patients get a good amount of blood work when they have myeloma and they’re on therapy is that we have a measure in the blood, or we have several measures in the blood, where we can monitor for relapse. So, we can look at the abnormal proteins, what we call paraproteins in the blood. Either as the M-spike, is what it’s called, or light chains. We look at both of those to see if there are increases in those numbers over time.

When a patient’s responding, those numbers come down. When a patient is losing response and their disease is progressing, that’s when we start to see those numbers go up. And that’s often an indication that we need to switch treatment, even before a patient develops symptoms related to their myeloma.   

What Are the Treatment Options for Relapsed/Refractory Myeloma?

What Are the Treatment Options for Relapsed/Refractory Myeloma? from Patient Empowerment Network on Vimeo.

What do relapsed/refractory myeloma patients need to consider when choosing a treatment approach? Expert Dr. Benjamin Derman explains the impact of previous therapies on options, various treatment classes available, and why combination treatments may be optimal.

Dr. Benjamin Derman is a hematologist and oncologist specializing in multiple myeloma at the University of Chicago Medicine Comprehensive Cancer Center. Learn more about Dr. Derman.

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Transcript:

Katherine:

Unfortunately, relapse is common among myeloma patients. Or it may be that a treatment stops working, and so the person’s myeloma becomes refractory.   

When considering a treatment for relapsed or refractory myeloma, are there different questions that patients should be asking their healthcare team?  

Dr. Derman:

Yeah. I mean, that’s a great question. I think part of it is every patient’s journey with myeloma ends up being quite unique, in part because we don’t have a lot of consensus in terms of how to treat myeloma. So, I may choose one regimen, but the other doc down the street is going to recommend a slightly different one. And now, they all have efficacy. No one’s going to be recommending something that’s not good, right? But what it means is that the journey, the number of therapies, the types of therapies that a patient has received are all going to be quite different than the next.  

So in part, sometimes the past therapies are going to dictate what options are available.  

So, I mentioned some different classes of therapies. The proteasome inhibitors, there’s a certain number of those. The immunomodulatory iMiDs, there’s a certain number of those. The CD38 monoclonal antibodies, there are those. And then there are a few other drug classes as well. 

And if we’re using three or sometimes four drugs at a time for each what we call line of therapy, meaning each time a patient changes treatment – right? Eventually, we’re going to have gone through a number of treatments that now the patient would be – their disease would be resistant to. And so, you don’t really – it’s not really going to be prudent or wise to go back to therapies that didn’t work previously.

And so, we start mixing and matching, and we come up with regimens that we think are going to hopefully throw a curveball to the myeloma to really try to get rid of it again. That’s what I mean by it’s dictated by past therapy.