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What’s the Latest in Emerging Myeloma Research?

What’s the Latest in Emerging Myeloma Research? from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Benjamin Derman shares research updates from the 2022 American Society of Hematology (ASH) annual meeting, including information about newly approved CAR T-cell therapies and a bispecific antibody therapy, as well as research on the new target, GPRC5D (G protein-coupled receptor 5D).

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

Related Resources:

What Are Current Myeloma Treatment Approaches

Understanding Myeloma Treatment Types

What Emerging Myeloma Treatments Are Showing Promise

Transcript:

Katherine:

Joining me is Dr. Benjamin Derman. Dr. Derman, welcome. Would you please introduce yourself?  

Dr. Derman:

Yeah. Thanks so much for having me. As you said, my name is Ben Derman. I’m an assistant professor at the University of Chicago. And I specialize in actually, plasma cell disorders, which is mainly multiple myeloma, amyloidosis, Waldenstrom’s. If a plasma cell is the problem, then I address it. So, that’s what I do. And that’s my clinical and research focus as well.  

Katherine:

Excellent. Thank you so much for taking the time to join us today. Before we get into our discussion about available myeloma treatments, let’s talk about emerging therapies. And I know there are many. 

The American Society of Hematology or ASH annual meeting took place in December. What are some of the highlights from that meeting?  

Dr. Derman:

Yeah, ASH is always a very exciting time because it’s when we get to see all the latest and greatest of what’s on the way or what’s already here to stay.  

I think the biggest focus in the myeloma field, if I could really pin it down, was more in the later stages of the disease and focusing on treatments in that setting. We already have two FDA-approved chimeric antigen receptors, or CAR T-cell therapies, in Ide-cel (Abecma), and Cilta-cel (Carvykti). Those are the brand names. And then more recently, we just had a bispecific antibody, which is another type of immune therapy that was approved. But there are actually many under investigation.  

And so, at this ASH we heard a lot. Not only about the target that’s been most popular in this setting, which is something called BCMA or B-cell maturation antigen.  

That’s what the CAR T-cell therapies that I mentioned are going after and the teclistamab (Tecvayli) bispecific antibody that I mentioned.

But there are a lot of other candidate drugs that are also targeting that same molecule. So, we heard a little bit about – more about those. We’ve been hearing about them pretty much at every conference these days.  

So, there’s a lot of competition in that space. Which is good for patients because ultimately, what we’re trying to figure out is, is one of these better than the others? Or at least, if we have multiple options, there may be different side effect profiles that we have to think about.

But now as BCMA therapies are getting used more and more, one of the questions is, well, is there any other target that we could go after? And really, the one that was hot at ASH this year was something called GPRC5D, or G-protein coupled receptor 5D. This is expressed pretty strongly in myeloma cells, and not in many other tissues. Maybe the skin, nails, tongue. So, basically, that’s what you want, is you want a target that’s not going to be expressed elsewhere.

So, there were a couple of different types of therapies that were discussed. One was a CAR T-cell therapy going after GPRC5D, and the others were – there were two bispecific antibodies actually targeting the same GPRC5D. And that’s actually already in addition to another GPRC5D-directed bispecific that’s in development.

So, basically, the idea is that if patients may experience progression on one of these BCMA targeting agents, we’re going to have another target to be going after. And I think that part is really, really exciting.

And as far as other highlights, I think the other thing is, how do we reduce the toxicity from these drugs? And exploring avenues in order to be able to decrease sort of the inflammatory effects of these drugs, which are important.   

How Can You Engage in Your Myeloma Treatment Decisions?

How Can You Engage in Your Myeloma Treatment Decisions? from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Benjamin Derman shares advice for partnering with your team when choosing a myeloma therapy, discusses important factors that should be considered, and provides key questions to ask your healthcare team to help you engage in your care. Dr. Derman also reviews research updates from the December 2022 American Society of Hematology (ASH) meeting.

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.

Download Resource Guide

See More from Engaging in Myeloma Treatment Decisions

Related Resources:

Understanding Myeloma Treatment Types

Expert Advice for Newly Diagnosed Myeloma Patients

Transcript:

Katherine:

Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to talk about myeloma treatments, what the options are both current and emerging, and how you can play a role in your care and treatment decisions.  

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.  

Well, let’s meet our guest today. Joining me is Dr. Benjamin Derman. Dr. Derman, welcome. Would you please introduce yourself?  

Dr. Derman:

Yeah. Thanks so much for having me. As you said, my name is Ben Derman. I’m an assistant professor at the University of Chicago. And I specialize in actually, plasma cell disorders, which is mainly multiple myeloma, amyloidosis, Waldenstrom’s. If a plasma cell is the problem, then I address it. So, that’s what I do. And that’s my clinical and research focus as well.  

Katherine:

Excellent. Thank you so much for taking the time to join us today. Before we get into our discussion about available myeloma treatments, let’s talk about emerging therapies. And I know there are many. 

The American Society of Hematology or ASH annual meeting took place in December. What are some of the highlights from that meeting?  

Dr. Derman:

Yeah, ASH is always a very exciting time because it’s when we get to see all the latest and greatest of what’s on the way or what’s already here to stay.  

I think the biggest focus in the myeloma field, if I could really pin it down, was more in the later stages of the disease and focusing on treatments in that setting. We already have two FDA-approved chimeric antigen receptors, or CAR T-cell therapies, in Ide-cel (Abecma), and Cilta-cel (Carvykti). Those are the brand names. And then more recently, we just had a bispecific antibody, which is another type of immune therapy that was approved. But there are actually many under investigation.  

And so, at this ASH we heard a lot. Not only about the target that’s been most popular in this setting, which is something called BCMA or B-cell maturation antigen.  

That’s what the CAR T-cell therapies that I mentioned are going after and the teclistamab (Tecvayli) bispecific antibody that I mentioned.  

But there are a lot of other candidate drugs that are also targeting that same molecule. So, we heard a little bit about – more about those. We’ve been hearing about them pretty much at every conference these days.  

So, there’s a lot of competition in that space. Which is good for patients because ultimately, what we’re trying to figure out is, is one of these better than the others? Or at least, if we have multiple options, there may be different side effect profiles that we have to think about.  

But now as BCMA therapies are getting used more and more, one of the questions is, well, is there any other target that we could go after? And really, the one that was hot at ASH this year was something called GPRC5D, or G-protein coupled receptor 5D. This is expressed pretty strongly in myeloma cells, and not in many other tissues. Maybe the skin, nails, tongue. So, basically, that’s what you want, is you want a target that’s not going to be expressed elsewhere.  

So, there were a couple of different types of therapies that were discussed. One was a CAR T-cell therapy going after GPRC5D, and the others were – there were two bispecific antibodies actually targeting the same GPRC5D. And that’s actually already in addition to another GPRC5D directed bispecific that’s in development.  

So, basically, the idea is that if patients may experience progression on one of these BCMA targeting agents, we’re going to have another target to be going after. And I think that part is really, really exciting.  

And as far as other highlights, I think the other thing is, how do we reduce the toxicity from these drugs? And exploring avenues in order to be able to decrease sort of the inflammatory effects of these drugs, which are important.  

Katherine:

That’s great. It sounds so promising. And all of that information is going to be very helpful as we move through today’s discussion.  

Let’s start with a general overview of treatment options. What types of treatment are offered for myeloma patients?  

Dr. Derman:

Right. So, if you think about at the point where a patient is diagnosed with myeloma, unfortunately, always a tough – always tough news to receive and to share with patients as well, we start to think about dividing treatment into phases. And in part, some of it’s going to depend on, what is the fitness level of a patient in front of me? And not so much age per se, but really fitness level. And what I mean by that is independence in their activities of daily living, their ability to walk, go up flights of stairs, carry out just their daily life.  

So, assuming that all options are on the table, we consider those patients to sort of be what we call stem cell transplant-eligible. 

And that picks a sort of variety of pathways that we can go down. And then the other variety of pathways we can go down are patients where either because of a comorbid conditions, there are other medical problems, or because of their fitness level, a stem cell transplant is not really going to be something that we consider.  

But either way, in either case, we start with something called induction therapy, where we’re aiming to induce a remission. Or induce a response as we typically say more commonly in myeloma.  

And usually that involves a combination of three or now possibly four drugs. And it’s really, really different the way that we treat myeloma than we treat other cancers. And what I mean by that is the traditional thought of using very harsh chemotherapy drugs that make people feel very sick, very ill, lose their hair, those kinds of things. Things that are maybe more outwardly associated with chemotherapy, we don’t see that with myeloma.  

In fact, I often tell patients if they’re fortunate to not have the disease affect them so much at diagnosis, a lot of people may not even know that they’re on treatment. And that can be good and bad, because they don’t know that what you’re going through, which can be challenging in its own right.  

So, really what we use are a combination of therapies. They can be oral drugs, they can be subcutaneous injections under the skin, or infusions. And one of the newer advances is using immunotherapy in myeloma. And this is a little different than it is in solid organ cancers like lung cancer or melanoma where immunotherapy is very popular as well.  

One of the main targets that we go after is something called CD38 on the surface of myeloma cells. And CD38 can be targeted with a type of monoclonal antibody.  

And there are two that are out right now, daratumumab (Darzalex) and isatuximab (Sarclisa). Daratumumab is actually approved to be used in the frontline setting, meaning at diagnosis. And that has really allowed us to augment the already – the backbone that we’ve been already using for quite some time in myeloma.  

Dexamethasone (Decadron), which is a steroid, is typically employed in all of these cases. And then we use drugs that are in the class of what’s called immunomodulatory iMiDs, chiefly lenalidomide (Revlimid) is the main one that we use in oral drug, and that’s been approved since 2006 or so.  

And then bortezomib (Velcade), which is something called the proteasome inhibitor, or its cousin carfilzomib (Kyprolis), can be used as well in the frontline. So, we’re usually combining these three or four drugs together in order to create this sort of symphony that really targets the myeloma from many different aspects.  

Katherine:

Yeah. How do patients know if they have any of these targets, such as CD38?  

Dr. Derman:

So, actually it’s interesting. CD38 is pretty much ubiquitously exposed on the surface and expressed on the surface of myeloma cells. So, it’s in a pathology report. It’s actually one of the ways in which we can identify what makes a plasma cell a plasma cell. But CD38 is one that is essentially ubiquitously expressed.  

And I say that with the idea that that expression may go down if you use these drugs to target that specific – that target. So, as time goes on, it’s not a drug that you may be able to reuse over and over. Or at least there might need to be a nice long break.  

Katherine:

So, obviously there are very – there are a lot of available therapies for myeloma. And I’m wondering what factors might impact treatment decisions. You did mention comorbidities. But what other factors are there?  

Dr. Derman:

Sure. And I think in part, it depends on if we’re talking about induction therapy or in the relapsed refractory setting. Let’s focus on induction therapy, right?  

So, there are some drugs that we’re typically going to employ pretty much universally. For those who are inclined to use that CD38 monoclonal antibody that I mentioned, it pretty much plays well with patients of all walks of life. So, that’s one where I feel really comfortable regardless.  

Lenalidomide is a drug that we don’t necessarily know from the get-go if there’s going to be a patient that’s not going to tolerate it well.  

We might reduce doses up front. But for the most part, that’s another drug that we’re typically going to use. I would say the one exception is for patients who have a simultaneous diagnosis of amyloidosis. And we know that in amyloidosis, lenalidomide may not be as well-tolerated.  

But actually, one of the key decisions that I’m often making in clinic myself is around that drug class that I mentioned earlier called proteasome inhibitors. And I mentioned two different drugs. There’s bortezomib and carfilzomib. And they actually come with very different side effects that I think are important to mention.  

Bortezomib is one that is typically associated with a high rate of numbness and tingling, what we call neuropathy in the fingers and toes. And about 75 percent of patients have been reported in the trials to get this. And most of it is what we call lower grade. But I’m not in the patient’s body, and I don’t know what that – what even a grade 1, which would be the lowest grade, really feels like. And if I have a mechanic, somebody who types for a living, a surgeon, somebody who uses their hands or their or rely on their feet for their day-to-day, that’s a scary prospect, right?  

The flip side is this drug, carfilzomib, is one that does not really cause nearly as much neuropathy, but has been associated with cardiac effects. Heart issues. And so, that can scare people, right? Heart’s important I hear. So, we have to be really careful in how we pick these therapies and talk about it with patients.  

Katherine:

Yeah. When we talk about making treatment decisions, it’s important to choose a therapy with your healthcare team.  

Let’s share some tips for having that conversation. I’d like to start with induction therapy, which is the first line of treatment for patients. What questions should patients ask when choosing therapy early in their diagnosis?   

Dr. Derman:

Yeah, that’s a great question. And it’s of course – it’s really the patient priorities I would say. So, one of the things that I like to discuss with patients is, number one, what are the things that they value? And that’s a hard question to ask without any qualifiers.  

So, one of the things that I often ask patients to think about is the – first of all, the number of visits to the medical center. Certain therapies are weekly, certain therapies may actually decrease in frequency overtime. So, if that is something, it’s hard to travel, it’s hard to get someone to take you or to come yourself, or you just don’t want to be in the clinic as much – right? If that’s your number one priority, there are going to be certain therapies that are – or regimens that may be better suited for that patient. If somebody says, “I don’t care how many times I have to come, my goal is the deepest response possible,” you can think about things from that standpoint.  

I mentioned side effects. What are the things that are scary to you personally, as a patient? Some people may look at that neuropathy, as I mentioned, and say “No way. That sounds horrible. I can’t do my job.” Other people would say, “I already have some cardiac issues. I don’t want to take that risk.” Right? So, there are different side effects that we have to take into account.  

Especially when it comes to talking about transplant, there is not just the acute issues that we have to deal with in terms of side effects, but also long-term immunosuppression. Meaning the immune system is suppressed, and there’s a risk of infections, and it’s going to be higher than if you had not gotten a transplant. So, those are at least some of the things that I encourage patients to be thinking about.  

I would also say, on top of that, patients may be approached about clinical trials. And I work at a university where we really value enrolling patients in clinical trials. But that they do come with some inconveniences as well, even though I think they really help to advance the field forward, and sometimes offer patients options they wouldn’t normally be able to get. But there are typically more visits associated with that, more evaluations, more blood draws, more bone marrow biopsies, so those are things that you really have to take into account.  

Katherine:

That’s great advice, Dr. Derman. 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.  

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.  

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. 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. 

Katherine:

Let’s get to a few audience questions, Dr. Derman.   

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.  

Katherine:

Yeah. Lauren wants to know, what is the best way to measure current immunity status? And should we mix COVID vaccine and flu vaccine?  

Dr. Derman:

Mm-hmm. This has become sort of a hot button issue all of the sudden over the last few years. Well, so, as far as immunity status, I wish there was a one good test that we could know.  

I mean, there are some features. Patients who have low white blood cell counts, especially low neutrophil counts, are certainly going to be at higher risk for infection. And that can happen due to myeloma, or more commonly, due to therapies. We can look at immunoglobulin levels, especially the IgG level. Patients who have IgG levels typically less than 400 milligram per deciliter seem to be historically at higher risks of infections. So, something called IVIG, which is an infusion of donated antibodies from plasma from healthy donors, can be used for that.  

There’s been a lot of discussion about, how do we know immune status related to COVID? And there are antibody levels that can be checked, but the truth is nowadays most people have high antibody levels, even if they’re on therapies because of the number of vaccines they received or natural infection. And it may not be a really good surrogate for understanding immunity to COVID. COVID’s outsmarted us time and time again, and probably will continue to do so.  

As far as the vac – I mean vaccines are super important. We do this for all our patients after transplant as well, revaccination them for all of their childhood vaccines. As far as the COVID and flu, I personally – I’m happy and feel fine administering both at the same time. We’ve seen no real safety signals there in my anecdotal experience. But I’m perfectly fine if patients want to split them up. It’s not something that is a 10 out of 10 for me. It’s more that it is as long as they’re getting both, I think that’s really important.  

Katherine:

Yeah. 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.  

Katherine:

Right. And so, there are lots of resources out there, it’s just asking your healthcare team what they are. Right.  

So, these were all really great questions, and we ask our audience to continue sending in questions to question@powerfulpatients.org. And we’ll work to get them answered on future programs.  

Dr. Derman, what advice do you have for patients? What would you like to leave the audience with?  

Dr Derman:

You know, myeloma is a funny – it’s a funny disease in the sense that patients who were diagnosed 10 years ago, who I still see, they remind me of the action movie where the building is maybe blowing up in the background, blurred out, and they’re running out of the building just in time. And that is because the pace of progress is fast enough in myeloma that we have all these new therapies coming down.  

So, really, I think maintaining hope and thinking about – don’t worry so much about what’s going to happen next. Figure out what you’re going to do now, and make sure that you’re living your best life now, and making sure that you’re doing what you can to treat your disease, I think, and help you feel good during that period too.  

Katherine:

Yeah.  

Dr. Derman:

So, I think it’s a message of hope mainly, that I feel really good about the future of myeloma. There’s a lot of innovation in this space that you can feel good about.  

Katherine:

Yeah. Dr. Derman, thank you so much for joining us today. It was a pleasure talking to you.  

Dr. Derman:

Likewise. Thanks so much.  

Katherine:

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.  

Myeloma Expert Gives an Overview of Novel Therapies

Myeloma Expert Gives an Overview of Novel Therapies from Patient Empowerment Network on Vimeo.

What novel multiple myeloma therapies are available for patients? Dr. Sikander Ailawadhi from the Mayo Clinic shares an overview of novel therapies of CAR T-cell therapy, monoclonal antibodies, bispecifics, and immunomodulators and discusses therapies currently in rapid development.

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Transcript:

Lisa Hatfield:

We are going to jump right into a discussion about some of the novel therapies that there is much buzz about right now, and it’s kind of an alphabet soup these novel therapies. I actually was trying to digest all of this information and divide it into the general categories.

And correct me if I’m wrong, but we have monoclonal antibodies, we have bispecific antibodies like the CAR-T therapies, and they target different things. We have BCMA, we have GPRC5D, FcRH5, we have things called antibody drug conjugates and cell mods. So, Dr. Ailawadhi, if you can just give us kind of a broad overview of these therapies and how they may be used to harness our immune system, and how they come into play when you’re treating your patients, how and when they come into play when treating your patients.

Dr. Sikander Ailawadhi:

Surely, so I think thanks a lot for bringing up that discussion, this is extremely important, and I think it’s most important because if a myeloma patient goes online and wants to search for information or research, these things start coming up this term start coming up. So it’s extremely important for a knowledgeable and empowered patient to learn about these, understand them, so that they are able to digest that information. And I should mention that a lot of what we’ll talk about about these particular treatments may not be applicable to newly diagnosed patients or a recently diagnosed patient, but this is important enough and exciting enough that I would want every single patient to pick up this information. Learn it hopefully, and maybe park it for now somewhere, so that hopefully down the road it becomes important and handy.

So you asked about monoclonals, bispecific, CAR-Ts, cell mols, etcetera. Let’s take a step back, let’s think about these as strategies to target myeloma. Myeloma treatment is going through a change where immunotherapy and harnessing the body’s own immune system is becoming extremely important, and when we do that, the immunotherapy is typically very targeted, so what these drugs these agents, these terms, this alphabet soup is doing is it is targeting specific markers on the myeloma cell on the plasma cell.

For example, one of the markers is CD38. There is a monoclonal antibody. There are actually two monoclonal antibodies. Daratumumab (Darzalex), rituximab (Rituxan) that are FDA-approved, but there are other ways of targeting CD38, for example, CD38 targeting CAR-T cells, CD38 targeting antibody drug conjugates, etcetera. So CD38 is one important part. A very, very, very important thing in the past one year or a year-and-a-half has been what’s called B-C-M-A, B cell maturation antigen. BCMA is another target on plasma cells. Very effective, very specific.

So there are many, many drugs that are available and becoming available to target BCMA. Right now, there are three drugs that are FDA-approved that can target BCMA. Two of them are CAR-T cells, a particular way of going after BCMA in which the body’s own T cells are collected. These are not stem cells, these are T cells, T lymphocytes, these T cells are collected, they are actually genetically modified to go and fight against the BCMA, and then those modified T cells are multiplied in the lab and given to the person as a drug, they go and seek the plasma cells because of BCMA kill them harnessing the body’s immune system.

So there are two CAR-T cells against BCMA, one called ide-cel (Abecma) and one called cilta-cel (Avekti). There has recently been available a bispecific antibody against BCMA, we call it bispecific because it connects to BCMA from one end and from a second it connects to the body’s T cells again, bring the T cells close to the plasma cells to kill them. Then bispecific antibodies called teclistamab (Tecvayli). And until recently there was another drug available against BCMA which was what’s called an antibody drug conjugate. This drug is called belantamab (Blenrep) for the timing, belantamab has been removed or withdrawn from the market in the U.S., but there are ongoing clinical trials and down the road, it may come back again.

Now, antibody drug conjugate is another way of targeting something in which there is a seeker for the BCMA in this case, and it has a payload of some kind of a toxin, so that when the drug connects to the plasma cell through the BCMA in this case, that toxin is released, it can kill the cell, so either we harness the body’s immune cells, the T cells by CAR-T or bispecific, or we kill the cell by releasing a toxic payload from a drug, antibody drug conjugate, these are all different methods of targeting the myeloma cell. So I talked to you about monoclonal bispecific CAR-T and ADC as different strategies, CD38 and BCMA, some of these strategies are available, but there are other targets which are very exciting and new drugs are being developed against them, two of the very interesting targets there one is called GPRC5D, and the other is FcRH5.

These GPR5CD or FcRH5 are two different targets on myeloma cells. No drugs are currently FDA-approved, but they are being developed very rapidly, and we have a couple of extremely promising agents which will be coming down the pipe. And you also mentioned something called cell mods. Cell mods are some newer drugs in the family of what’s called IMiDs or immunomodulators, in which our patients may be aware of thalidomide (Thalomid), lenalidomide (Revlimid), and pomalidomide (Pomalyst). The cell mods are kind of the same family, and there are a couple of them that are also being developed.

So why is this important for everybody, whether they are newly diagnosed or relapsed or long-term survivor with myeloma, because this tells you that not only are we getting newer drugs in the same classes, we are also getting brand new classes of drugs, and you can imagine that means that those brand new strategies are ways to target the plasma cell, we know cancer cells are smart and they develop invasive mechanisms to become resistant to drugs, but every time something gets resistant if we have a brand new mechanism to go against the disease, but that’s exciting because that’s why we are seeing deeper responses, even in very heavily pre-treated patients, because we are using newer specific, relatively safe, convenient strategies to going after the plasma cell.

I know that was a lot of information, but I hope this helps our listeners learn a little bit about what you rightly said is an alphabet soup, but I would like us to think about it as an exciting time for being a myeloma doctor, and certainly a very hopeful situation for all our patients. 

How Is Myeloma Treatment Response Measured?

How Is Myeloma Treatment Response Measured? from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Betsy O’Donnell reviews the terms that define myeloma treatment response, such as complete remission (CR) and partial remission (PR). Dr. O’Donnell goes on to discuss the new tools that are being used to monitor treatment effectiveness, including MRD (minimal residual disease).

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.

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Transcript:

Katherine Banwell:

Dr. O’Donnell, Alex wrote in with this question. “What is the difference between a complete response, VGPR, and PR as it applies to prognosis and maintenance after an autologous stem cell transplant?” And before you answer the question, would you define VGPR and PR for us?   

Dr. Betsy O’Donnell:

Sure. So, we have different criteria that help us understand how well a drug is working, and they’re uniformly used across clinical trials so that we’re all speaking the same language. And so we talk about a PR, a VGPR, and a CR. So, a CR is a complete response, which is 100 percent of that monoclonal protein that we initially detected is gone. We can’t measure it. Or if you have an elevated light chain, which is another piece of the protein, that has gone back down to normal. 

Taking that a step further, astringent CR is if we do a bone marrow biopsy and we can’t find any cancer plasma cells in there. A VGPR is where we see a 90 percent reduction in the amount of protein we can measure, and a PR is anything over – a partial response is anything over 50 percent. 

So, that’s a language we speak really just so that when we’re interpreting clinical trials, we all are using the same criteria. 

And so these are different terms that classify it. If the example that you gave, someone’s had a transplant, what would typically happen 100 days after that transplant is a patient would restart maintenance therapy.   

The classic maintenance is just lenalidomide (Revlimid), which is the pill that they were probably taking before that. And there’s a lot of controversy now but no good answers about changing therapy after a transplant, if you haven’t received a deep response. 

What we do know is that after a transplant, when someone goes on lenalidomide maintenance, they continue to respond. So, the greatest depth of response is not necessarily achieved in the induction phase or right immediately after transplant, but over time on maintenance. 

There’s another tool that we’re now using and incorporating, both in terms of how we assess treatment but also potentially in how we modify treatment, which is something called minimal residual disease, MRD, which goes a step beyond. When people have astringent CR, a CR, looking for really just traces of the disease on a molecular level.  

And all of those help us understand how well the patient has responded and how long that remission might last, but they’re not definitive in terms of how we should adjust treatment based on those right now. 

How Is Relapsed or Refractory Myeloma Managed?

How Is Relapsed or Refractory Myeloma Managed? from Patient Empowerment Network on Vimeo.

Drs. Irene Ghobrial and Betsy O’Donnell discuss next steps if myeloma relapse occurs or the disease doesn’t respond to treatment. The experts review the necessary tests following a myeloma relapse and how a treatment choice is determined.

Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Learn more about Dr. Ghobrial.

Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders. 

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Transcript:

Katherine Banwell:

We know that relapse can happen. Dr. Ghobrial, how common is relapsed or refractory disease? 

Dr. Irene Ghobrial:

Yes, and, fortunately, we do have amazing remissions. We have very long remissions. Many people are living 10 years, 15 years and longer, which as Dr. Nadeem said, was not something we knew about years ago. I trained 20 years ago as a fellow, and myeloma was a survival of three to five years.  

We’ve come a long way, but we want to change that even better. We want a cure. We want to tell a patient, “You are done. You’re cured,” and we will not stop until that happens. So, when people have a progression again or relapse, then we want to consider what is the next available option. What is the best option to give them yet one more long, long remission? We are failing sometimes, and that’s because the disease is so bad, the biology of the disease is so bad, and the drugs that we’re using may not be the best drugs for that patient. 

And that’s why we need to understand better the biology and pick the right drugs for the right patient up front as much as we can, and also think about earlier treatment. We were just saying we probably have amazing drugs, but we’re waiting way too long until people have almost metastatic disease, and then we treat them. Why not think of an earlier interception when the disease is less mutated, when you have less cancer cells, a better immune system, and use your best drugs then? And hopefully we will achieve cure in many of those patients. 

Katherine Banwell:

What testing takes place after a relapse? Is it different than what has happened before, the testing that was done before? 

Dr. Irene Ghobrial:

No, the same tests exactly. We sort of say it’s restaging. We check everything again – the bone marrow biopsy, the FISH, because you may now develop a 17p that was probably there, but the very, very small number of cells that you cannot detect, and now it grows because of something called chrono selection. The drugs kill the sensitive cells, but they don’t kill the bad cells, and that’s how we can get all of those changes and mutations.  

Katherine Banwell:

Okay. Dr. O’Donnell, is the process for choosing treatment different for a relapsed or refractory patient? 

Dr. Irene Ghobrial:

So, that’s a great question. Yes, it can be. I mean, again, it always depends on how the person is doing at that time. It also depends, there are certain drugs that may not be approved in the front lines, something like venetoclax (Venclexta). If a person has a specific translocation, this 11;14, that’s something that we would like it in a second-line setting, for example. 

Usually one of the big questions people ask is if you’re on a specific class of drugs, should you change classes? So, this example is if you’re on lenalidomide (Revlimid), and you have evidence that your disease is progressing, should you change to a different type of drug? A proteasome inhibitor, monoclonal antibody? Should that include one of the same classes of drug, like pomalidomide (Pomalyst), which is the next generation? 

So, there are a lot of different factors that we consider. The number of drugs. So, you know, as Dr. Nadeem said, historically – there’s a lot of history in myeloma therapy, and it’s been an evolution, and so now we’ve had people who were treated with the three-drug combination that are starting, after many years, to progress. So, we might choose a monoclonal antibody for those patients because it wasn’t available at the time they were diagnosed. Versus patients now, who are typically on a four-drug regimen that includes those monoclonal antibodies and all the different classes of drugs. 

We’re looking at different and, if available, novel agents to put those patients on. And again, I think Dr. Nadeem made a really important point that I want to underscore, which is that very often our best therapies are available in clinical trials. And so when and if there is the opportunity to be on a clinical trial, you may be then able to get something that would not otherwise be available to you. So, I encourage people to always have an open mind to being on a clinical trial at any stage in their disease treatment. 

Katherine Banwell:

What therapies are available for relapse or refractory disease? Are they different than other therapies? 

Dr. Betsy O’Donnell:

You know, so that’s a great question. So, yes and no. I highlighted one example that might be a little bit different, but in general, we’re very fortunate that we have multiple classes of drugs, meaning we have different drugs that work differently to kill your myeloma cells. And as Dr. Nadeem said earlier, we use those in combinations to increase the effectiveness of those medicines. Within each class we have a variety of drugs. 

You used the example of immunomodulators, and show that we have three different of those type of drugs.   

We have two different proteasome inhibitors. Beyond that, we have other classes of drugs that were mentioned. We have monoclonal antibodies, immunotherapies.  

And so very often we make, it’s almost like a mix where we pick what we think is going to be most effective, sometimes based on cytogenetics. The biology. Sometimes based on patient selection. What are their other medical problems, what are their current issues? And we pick the combination that we feel is going to be most effective from the different classes of drugs that we have together, usually trying to use multiple drugs in combination. 

Katherine Banwell:

Well, what newer therapies are available or in development for refractory and relapsed disease? 

Dr. Betsy O’Donnell:

So, I think that the greatest interest that I think we’re all most excited about is the immunotherapy space, and I think we’ve seen – for myeloma, we see that this is a relapsing and remitting disease. 

And what’s been so exciting about CAR-T cells and the bispecific antibodies is that in patients who have had, on average, five relapses, we’re seeing tremendous results. So, complete remissions or very good partial remissions that last. In fact, can last up to two years, on average, with one of our CAR T-cell products. 

So, this is really exciting, especially when you compare to what historically has been out there for patients who have had that many relapses. And just as Dr. Nadeem said, the way that drugs enter, they enter from the relapse refractory setting, ethically that’s what makes the most sense, and they march their way forward. And so that process is happening right now as we speak, and I think like Dr. Ghobrial talked about, is the importance in early disease of thinking about using these really exciting therapies in patients who have lower burdens of disease with a goal of cure. 

And so I think all of us on this call are committed to one thing, and that is curing multiple myeloma, and even the precursors that lead up to it so that patients never have to go through the process of years and years of therapy. And so I think we’re very excited about what immunotherapy might be able to offer as we move forward in myeloma treatment. 

How Are Patients on Myeloma Maintenance Therapy Monitored?

How Are Patients on Myeloma Maintenance Therapy Monitored? from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Omar Nadeem explains how a follow-up care and monitoring plan for patients on maintenance therapy is determined.

Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.

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Transcript:

Katherine Banwell:

Dr. Nadeem, many patients are on maintenance therapy following active treatment. So, how is a patient on maintenance therapy monitored? 

Dr. Omar Nadeem:

Yes, so, majority of the time just with blood work. We don’t necessarily need to do a lot of bone marrow biopsies and PET scans for a majority of patients that are on maintenance therapy unless we’re either worried about their blood markers or some symptoms. Generally speaking, any time – it depends on what maintenance therapy they’re on, of course. If they’re just on lenalidomide (Revlimid), which is the most commonly used maintenance therapy, a lot of times we check in with them every one to three months. 

Depending on how their disease status is and how they’ve been doing and whether there’s any side effects that we need to worry about. So, they still have to see their doctors, still have to get the blood work. Usually you can get away with having it done no more than once a month or so, unless they are on other medications along with Revlimid, where we then have to check in with them a little bit more frequently. 

And some of that changes, so patients can be on maintenance therapy for five plus years, and we get a very good sense of how they are doing and kind of how their disease is doing, and we can kind of be a moving target in terms of the frequency of the follow-ups. 

Understanding Myeloma Treatment Types

Understanding Myeloma Treatment Types  from Patient Empowerment Network on Vimeo.

What are the types of treatment available for myeloma? Myeloma expert Dr. Mark Schroeder reviews the myeloma treatment classes, including proteasome inhibitors, immunomodulatory drugs (iMids), and immunotherapy. Dr. Schroeder also discusses factors to consider when choosing therapy for patients with myeloma. 

Dr. Mark Schroeder is a hematologist at Siteman Cancer Center of Washington University School of Medicine in St. Louis. Dr. Schroeder serves as Associate Professor in the Department of Medicine. Learn more about Dr. Schroeder.

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Transcript:

Katherine Banwell:

There are a number of treatments for myeloma patients. Can you talk about the types that are available? 

Dr. Mark Schroeder:

Yeah. So, the classes of – actually there is lots of drugs approved for treating myeloma but also recently approved.  

And we classify them into big categories. One of the categories is called immunomodulatory drugs – those are drugs like lenalidomide (Revlimid) and pomalidomide (Pomalyst), or even thalidomide (Thalomid), which was one of the first immunomodulatory drugs. Those are oral drugs that work on a specific pathway in the myeloma that leads to the myeloma cell dying. Another class of drugs are called proteasome inhibitors. Those include drugs like bortezomib or carfilzomib. Those drugs are often given under the skin or in the vein, and we know that they work really effectively on their own, but also when we combine them with an immunomodulatory drug like Revlimid or pomalidomide, the effect is even better. Another class is steroids. Steroids are kind of one of the first drugs used to treat this cancer, and steroids are effective at treating myeloma cells.  

Plasma cells are responsive to steroids. One of the first treatment regimens used to treat myeloma were traditional chemotherapies, and those are usually reserved for later on. You might think of traditional chemotherapy that causes hair loss, nausea, vomiting, low blood counts. Those, decades ago, were used to treat myeloma, but now we have effective oral, IV, or injection into the skin that don’t cause a lot of the traditional chemotherapy side effects but are very effective at treating the myeloma. And then another major class of drugs are considered immunotherapies. So, these are treatments that are engineered to either stimulate the immune system to go attack the myeloma, or maybe it’s even using part of your own immune system to engineer it to go attack the myeloma. 

Examples of those are called bispecific antibodies which kind of binds to the myeloma but binds to an immune cell, brings them together, or a CAR T-cell which takes your own T cells genetically modifies them to attack the cancer. 

Katherine Banwell:

And there is also a bone marrow transplant. Is that right? 

Dr. Mark Schroeder:

That’s right, yeah. I neglected – so, bone marrow transplant has been around for a while in myeloma. And despite it being around for so long and really good therapies being approved for myeloma, it’s still a standard treatment for myeloma. And bone marrow transplant in myeloma uses a traditional chemotherapy called melphalan that is associated with the chemotherapy side effects we talked about. But the advantage of bone marrow transplant is that it prolongs the time before the myeloma comes back and needs other treatments, and that’s why we do it. It can be toxic, but it can prolong the time before a patient needs another line of therapy. 

Katherine Banwell:

We know that everyone’s diagnosis is different. So, how do you determine a treatment plan for an individual patient? 

Dr. Mark Schroeder:

So, it depends in terms of the patient – initially, I will evaluate patients and determine how fit they are. Is it a patient that I think is strong enough to undergo a stem cell transplant? Is that going to be a benefit to them? That’s not necessarily a factor of just age, but it’s also, are they doing well functionally, or do they have any other medical problems like heart disease or kidney problems? Those things play into my decision on a treatment initially with patients.

So, whether you’re fit or unfit will help to guide what your treatment is going to be in general. Fit patients are somebody that could undergo multiple treatments, go through a transplant, have minimal toxicity, and recover fully after more intensive treatments.  

Whereas, unfit may need more assistance, and we tend to reduce the intensity of treatments. It doesn’t mean the treatments, if you’re unfit, are less effective – they can be very effective. But our goals for treatment change in that situation. And we’re looking for responses but also looking for quality of life. And then it changes also depending on the genetics of the myeloma. Our treatment for patients who have genetic changes that are high risk will change compared to those that have what are called standard risk genetic changes.  

So, that is an important point to discuss with your oncologist if you have – Do I have standard risk or high-risk genetic changes in my cancer? And does that effect my treatment? And then also, treatment in somebody who is being treated a second time or third time or beyond for their myeloma depends on what treatments you had before and how effective they were.  

And what were your toxicities or side effects from those treatments? So, all those factors play into a decision of treatment for an individual. 

What Do You Need to Know About Follicular Lymphoma?

What Do You Need to Know About Follicular Lymphoma? from Patient Empowerment Network on Vimeo.

What should you and your loved ones know after a follicular lymphoma diagnosis? This animated video provides an overview of follicular lymphoma, current treatment options, and important steps for engaging in your care.

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Transcript:

What do you need to know if you or a loved one has been diagnosed with follicular lymphoma? 

Follicular lymphoma is a type of B-cell non-Hodgkin lymphoma. It is typically slow-growing and can begin in the lymph nodes, bone marrow, or other organs. The disease does not always cause symptoms. But if symptoms are present, they can include swollen lymph nodes, fever, unintentional weight loss, and night sweats.  

Follicular lymphoma is classified as “low grade” if the disease is slow-growing, or “high grade,” if the disease is more aggressive and growing more rapidly. 

Follicular lymphoma is staged to understand where the lymphoma is in the body and to help determine which treatment options are best. There are four stages – 

  • Stage I, in which the lymphoma is localized in one single lymph node area or one non-lymph node site. When there is a non-lymph node site involved, an “E” is added to the stage, meaning “extra nodal.” 
  • In stage II, the lymphoma is in two or more areas on one side of the diaphragm. Again, “E” designation means that there is a non-lymph node site involved. 
  • Stage III means the lymphoma is in two or more lymph node areas above and below the diaphragm. 
  • And finally, stage IV is when the lymphoma is widespread, with involvement above and below the diaphragm, including at least one non-lymph node site. 

Unlike in many other types of tumors, stage IV follicular lymphoma is often very treatable, because lymphomas tend to be sensitive to many different therapies. 

Treatment recommendations are based on a variety of factors, including: 

  • Disease stage 
  • Tumor size and tumor grade 
  • Disease symptoms 
  • And a patient’s age and overall health 

For some patients, treatment doesn’t begin right away, and an approach called “watchful waiting,” “observation,” or “active surveillance” is used to monitor the progression of the disease. This usually involves regular oncology clinic visits and lab checks – and sometimes repeat imaging scans. 

When it is time to treat, options may include: 

  • Radiation therapy 
  • Chemotherapy 
  • Targeted therapy 
  • Immunotherapy 
  • Or cellular therapy, such as CAR T-cell therapy or a bone marrow transplant.
  • Your physician may also recommend clinical trial options. 

Now that you understand more about follicular lymphoma, how can you take an active role in your care?  

  • First, continue to educate yourself about your condition. Ask your healthcare team to recommend credible resources of information.  
  • Next, understand the goals of treatment and speak up about your personal preferences.
  • Consider a second opinion or a consult with a specialist following a diagnosis to confirm your treatment approach.
  • And, write down your questions before and during your appointments. Visit powerfulpatients.org/FL to access office visit planners to help you organize your thoughts. Bring loved ones to your appointments to help you recall information and to keep track of important details.
  • Ask your doctor whether a clinical trial might be right for you.
  • Finally, remember that you have a voice in your care. Don’t hesitate to ask questions and to share your concerns. You are your own best advocate. 

To learn more about follicular lymphoma and to access tools for self-advocacy, visit powerfulpatients.org/Follicular. 

Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma

Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma from Patient Empowerment Network on Vimeo.

Dr. Abdullah Khan, of Ohio State University Comprehensive Cancer Center – The James, reviews currently available treatments as well as those in development for patients with relapsed or refractory myeloma. 

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

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Relapsed and Refractory Myeloma Defined

Transcript:

Katherine:

Are there any recent advances in treatment for patients with relapsed or refractory disease?  

Dr. Khan:

Currently and in the past 20 years or so, we’ve seen about 20 approvals for new drugs for patients with multiple myeloma. The way the approval process works it typically looks at the effectiveness of a drug in the relapsed refractory setting first. And after establishing the safety and efficacy, the therapies are moved earlier in the disease course.   

The great example of this are the anti-CD38 monoclonal antibodies daratumumab and isatuximab. They were first approved in the relapsed refractory setting in combination with other antimyeloma treatments. And due to their impressive effectiveness and relative safety, they’re already being used in the frontline setting for patients with newly diagnosed multiple myeloma.   

In the newly diagnosed setting, a commonly cited study is the phase two GRIFFIN trial. And that added daratumumab to the BRd, or bendamustine (Bendeka, Treanda), lenalidomide (Revlimid), dexamethasone backbone.  

And Europe, they completed the phase three study of adding isatuximab, the other anti-CD38 monoclonal antibody to the BRd backbone. And what we’re finding what was very effective in the relapsed refractory setting was actually adding to the efficacy of newly diagnosed treatment regiments. As a side note, these trials – there are also trials looking at daratumumab and isatuximab in the smoldering myeloma phase, so moving it even earlier.  

I think one of the most attractive new targets in myeloma is targeting this antigen called B-cell maturing antigen, and a number of therapies are being developed or are already developed for it. The first approved was belantamab mafodotin, and this is an antibody drug conjugate. 

So, when the antibody binds to BCMA on the multiple myeloma cells, it releases its toxic payload into the myeloma cell. And so, it’s very effective towards myeloma, and no other good cells or fewer other good cells are affected by it. To provide some numbers, in patients with a median of seven prior lines of treatments, meaning their myeloma had relapsed that many times, the response rate was about 30 percent. And a fifth of those patients had VGPR, very good partial response, or better response.  

There are also bispecific antibodies that target this myeloma marker, and we anticipate getting one approved soon in the U.S. called teclistamab. Teclistamab is an antibody that binds both CD3 on T cells of the immune system and B-cell maturating BCMA on the myeloma cells. 

So, the way this antibody kills myeloma is by activating the T cells, the immune system, and directly killing the tumor. So, this was recently published in the New England Journal of Medicine. And in people who were treated with at least five prior lines of therapy, the response rate was about 63 percent, and the median progression-free survival, or the time until the myeloma progressed, was about 11 months.  

We were very active in a clinical trial looking at the effectiveness of another antibody, a bispecific antibody, called Regeneron 5458. In a similar patient population, the response rates were 75 percent in the higher-dose level group, and right now it’s actually a bit too early to tell how long the progression free survival is or the duration of response. 

There are also other bispecifics in development targeting other myeloma markers ssuch as talquetamab, that binds to a marker called GPRC5D, and cevostamab, which binds to a marker called FcRH5. The response rates as single agents in patients with relapsed refractory multiple myeloma are 66 percent and 45 percent respectively. These are all incredible numbers for a single drug in the relapsed refractory setting.  

What You Should Know About DLBCL Treatment Side Effects

What You Should Know About DLBCL Treatment Side Effects from Patient Empowerment Network on Vimeo.

Once a patient begins diffuse large B-cell lymphoma (DLBCL) treatment, what side effects could they experience? Dr. Kami Maddocks, reviews potential side effects and how they may be managed.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks.

See More From The Pro-Active DLBCL Patient Toolkit

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Transcript:

Katherine:

What are the side effects that patients can expect with these treatments?  

Dr. Maddocks:

So, when they get the treatment, on the day they get it, there can be an infusion reaction to the rituximab or antibody therapies. So, the first treatment, that treatment is given very slowly and titrated up. If patients have a reaction, we stop it, treat the reaction, and then they’re able to continue therapy but again, that first day, it can take several hours for that one antibody to get in. And then, later, therapies are given at a more rapid pace.   

So, about 70 percent of people who react, it can be really almost anything. Some people get flushing, some people will get a fever, some people –have shortness of breath or their heart rate will go up. 

Katherine:

Okay. All right. Any other side effects? 

Dr. Maddocks:

Yeah. So then chemotherapy is meant to kill cells during the cell cycle. So, cancer cells divide more rapidly, chemotherapy is targeting them, but it also effects good cells in the body, specifically those that divide at a more rapid pace. The biggest risk of chemotherapy is infection.  

So, it effects the good white blood cells that fight infections. It can affect your red cells that carry your iron, gives you your energy. Or your platelets which help you to clot or not bleed when you get caught. So, infection is the biggest risk of chemotherapy. So, usually, with this regimen, that infectious risk is highest within the second week of treatment, that treatment is given every three weeks.  

So, we tell patients they should buy a thermometer, check their temperature, they have to notify their doctor or go to the ER if they have a fever. Besides infection, there’s a small percentage of patients who might need a transfusion. GI toxicity. So, nausea, vomiting, diarrhea, mouth sores, constipation, all of which we have good treatments for. So, we give medication before chemo to try to prevent people from getting sick and then give them medicine to go home with, if they have any nausea. We can alter those medications as time goes on, if they’re having any problems. So, we just need to know about it. Most patients will lose their hair with this regimen.  

It can affect people’s tastes, it can make their skin more sensitive to the sun, and then, less common but potential side effects are it can cause damage to the nerves. Or something we call neuropathy, which most often patients will start with getting numbness or tingling in their fingers and toes, and we can dose adjust if that’s causing some problems.  

And then, there’s a risk to the heart with one of the drugs. So, the heart should pump like this. The heart pump function can go down. So, we always check a patient’s heart pump function before they get their chemo, to make sure that they’re not at higher risk for that to happen.  

Katherine:

So, all of these approaches are used in initial treatment?  

Dr. Maddocks:

Mm-hmm. 

Katherine:

Okay. 

Is My DLBCL Treatment Working? What Happens If It Doesn’t Work?

Is My DLBCL Treatment Working? What Happens If It Doesn’t Work? from Patient Empowerment Network on Vimeo.

Diffuse large B-cell lymphoma (DLBCL) expert Dr. Kami Maddocks describes how a treatment’s effectiveness is evaluated and reviews the options available for refractory patients.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks.

See More From The Pro-Active DLBCL Patient Toolkit

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Transcript:

Katherine:

So, how do you know if a treatment is working?  

Dr. Maddocks:

So, as far as evaluating treatment, you get a scan before you start treatments, so we know where all the lymphoma is at. And then, typically, you get some sort of scan in the middle of treatment, and then after, you complete your six cycles of treatment. Or for early stages, sometimes patients will get less than six cycles. So, we get scans to make sure it’s working. So, you can tell by those things, how much has gone, hopefully all of it has gone by the end. Occasionally, patients that had a lot of symptoms to start with, their symptoms will go away, and then they’ll start coming back.  

This is less common, because the majority of patients do respond to chemotherapy. It’s less common to get patients who are what is called refractory, meaning they don’t get any response to therapy. So, occasionally they’ll note symptoms but a lot of times, we’ll see something on that mid-therapy or end of therapy scan, if it’s not going to make it all go away.  

Katherine:

So, if a treatment doesn’t work, what happens then?  

Dr. Maddocks:

If treatment doesn’t work, it depends a little bit – and now it depends a little bit on the timing of that treatment not working. So, it used to be that patients who were eligible for treatment, no matter if it didn’t work right away or if it put them into what we call a remission, so there’s no evidence of disease and then it relapsed, they would have the option of further chemotherapy and then an autologous stem cell transplant. So, a bone marrow transplant where they donate their own cells.  

If they were in a good enough health or if they were not – to do that, you have to donate your own bone marrow cells and as we age, we make less bone marrow cells. So, once you reach a certain age, your body can’t produce enough cells to donate to a transplant. In those patients, we offer them less aggressive chemo options, which were not known to be curable but could put them into remission again, for a while. More recently, there has been some that chimeric antigen receptor T-cell therapy that I mentioned where you actually donate your own T cells. So that’s –. And your lymphoma is of your B cells.  

Your T cells are in another immune cell that should recognize that lymphoma is bad and attack it, and they’re not functioning properly. So, you donate your own T cells, and they’re sent off and reengineered to target a protein on the tumor. Then, you get those cells back, and they’re meant to target the lymphoma and kill the lymphoma cells.  

So, that is now an approved therapy for patients who don’t achieve the remission – so, who’s first chemo doesn’t work or if they relapse within a year of completing chemo. So, that’s a possibility. The chemo and transplants a possibility. Or there’s other approved therapies now, that can be given as second options or third or later options, which have been shown to keep patients in remission for a while.  

Katherine:

Dr. Maddocks, you touched up on this a moment ago, but what are the approaches if a patient relapses? What do you do?   

Dr. Maddocks:

So, you would rework them up if they relapsed. Similar to that, if they relapse within a year and they have access to the CAR-T and they’re healthy for that, then that’ll be an option. The second type of chemotherapy in the transplant. So, you can’t just go straight to a transplant. You have to get a different type of chemotherapy to try to get the disease under control again, before you would go to a transplant.  

Or there’s a number of other targeted therapies that are approved. So, there’s other – I talked about rituximab (Rituxan) is given in the first line, that targets a CD-20 protein, there’s an antibody that targets a CD-19 protein that’s given out in relapse. There’s another antibody drug – there’s actually two antibody drug conjugates. So, an antibody that targets the protein on the cells that are attached to a chemo, that’s given. Or there’s different chemotherapy and then even some oral therapies.  

Katherine:

Okay. So, there’s a lot of different options available for people.  

Dr. Maddocks:

Correct. And there’s always clinical trials. So, there’s always the option to find something where we’re studying some of these newer therapies. They’re therapies in combination.  

Understanding DLBCL Treatment Classes

Understanding DLBCL Treatment Classes from Patient Empowerment Network on Vimeo.

Dr. Kami Maddocks reviews diffuse large B-cell lymphoma (DLBCL) treatment approaches, including options for patients who are considered high-risk or who have relapsed. Dr. Maddocks goes on to review which factors are considered when selecting a therapy and the potential for curative treatment.

Dr. Kami Maddocks is a hematologist who specializes in treating patients with B-cell malignancies at the The Ohio State University Comprehensive Cancer Center – The James. Learn more about Dr. Maddocks.

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Transcript:

Katherine:

Let’s turn to treatment options. Is a person with DLBCL treated right away?  

Dr. Maddocks:

They’re treated pretty quickly after the diagnosis. So, typically, when somebody has a diagnosis, they undergo a number of different tests, including lab work, imaging work, sometimes for their biopsies.  

So, that information is gathered over days to sometimes a few weeks process. Then, when you have all that information, you go over the results, go over the treatment at that time. So, it’s typically treated not within, usually, a day of diagnosis but it’s not something that you spend weeks or months before treating.  

Katherine:

Yeah. What are the different types of treatments available?  

Dr. Maddocks:

So, the diffuse large B-cell lymphoma is treated with chemotherapy and immunotherapy. So, a combination of an immune antibody therapy and chemotherapy. There is a role in some cases for radiation, but never just radiation alone and never just surgery alone. So, there’s always what we call a systemic treatment so, a treatment that goes everywhere. Because this is considered a blood cancer, it’s a cancer of those cells, it can really spread anywhere.  

And so, just cutting it out with surgery or just radiating the area doesn’t treat everything, even if you can’t identify it.  

Katherine:

Can you get specific about some of the treatment classes?   

Dr. Maddocks:

Yeah. So, the most common treatment for diffuse large B-cell lymphoma is a chemo immunotherapy called R-CHOP. So, this is three chemotherapies and antibody therapy that’s direct called rituximab (Rituxan) that’s directed at a protein on the lymphoma cells. And then, a steroid called prednisone, given with the chemo and then for a few days after. There was a study that recently showed an improvement with switching one of those drugs with another immunotherapy that’s an antibody conjugated to a chemo drug. But that’s not yet been approved. There are clinical trials available. So, looking at these treatments that might be new or combining therapies with this standard treatment.  

And then, very occasionally, there are certain features of diffuse large B-cell lymphoma. There are particular few different subtypes that are classified a little bit differently, that are treated within an infusional therapy called Dose Adjusted R-EPOCH.  

Katherine:

What about stem cell therapy? Is that used?  

Dr. Maddock:

Stem cell therapy is used in the relapse setting. So, if a patient doesn’t go into a remission or if they relapse after achieving a remission with their chemotherapy, then stem cell transplant is an option. So, there are actually two different types of stem cell transplant. One from yourself and one from somebody else. In lymphoma, we typically do one from yourself, where you donate your own cell before. But we don’t use that as part of the initial treatment.   

Katherine:

So, if somebody is high risk, Dr. Maddocks, is the approach different for them? 

Dr. Maddocks:

So, it depends. We define high risk in different ways. So, there’s a specific type of lymphoma called double hit lymphoma, where there’s a few chromosomal translocations associated with the lymphoma, that we give a little more aggressive chemo immunotherapy regimen. There are also other subtypes, including a rare type of lymphoma called primary mediastinal B-cell lymphoma. Again, categorized a little bit different but sometimes included as a large cell lymphoma. We also give that treatment for.   

Katherine:

Okay. So, there’s a lot of different options available for people.  

Dr. Maddocks:

Correct. And there’s always clinical trials. So, there’s always the option to find something where we’re studying some of these newer therapies. They’re therapies in combination.   

Katherine:

Is a cure possible?  

Dr. Maddocks:

Yes. A cure is possible. When you look at patients who are treated with initial chemotherapy, we cure somewhere between 60 percent to 70 percent of patients with the initial chemotherapy. If patients’ relapse, depending on their age and their condition, they’re candidates for other therapies.  

And therapy including other chemo and stem cell transplant is potentially curable in some patients. And then, there’s a newer therapy called chimeric antigen receptor T-cell, or CAR T-cell therapy, which also looks like it’s curing a subset of patients who relapse or don’t respond to initial therapy.  

Making Myeloma Treatment Decisions at Every Stage of Care

Making Myeloma Treatment Decisions at Every Stage of Care from Patient Empowerment Network on Vimeo.

Dr. Mark Schroeder, of Siteman Cancer Center, reviews the types of treatment approaches available for patients with myeloma, discusses how therapies are chosen and why, including in the relapsed and refractory setting. Dr. Schroeder also shares an update on new and emerging myeloma therapies.

Dr. Mark Schroeder is a hematologist at Siteman Cancer Center of Washington University School of Medicine in St. Louis. Dr. Schroeder serves as Associate Professor in the Department of Medicine. Learn more about Dr. Schroeder, here.

See More from Engaging in Myeloma Treatment Decisions

Download Resource Guide

 

Related Resources:

Expert Advice for Newly Diagnosed Myeloma Patients

The Role of a Myeloma Specialist on Your Care Team

How Is a Myeloma Patient in Active Treatment Monitored?

Transcript:

Katherine Banwell:

Hello, and welcome. I’m Katherine Banwell, your host for today’s webinar. Today’s program is about how to actively engage in myeloma treatment decisions at every stage of your care. 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. Well, let’s meet our guest today. Joining us is Dr. Mark Schroeder. Dr. Schroeder, welcome. Would you please introduce yourself?  

Dr. Mark Schroeder:

Yeah. Hi, Katherine. Thanks for having me. I’m Dr. Mark Schroeder. I’m an Associate Professor of Medicine at Washington University School of Medicine in St. Louis. 

Katherine Banwell:

Thank you so much for taking the time out of your day to join us. As I mentioned, this webinar is about actively engaging in myeloma care decisions. So, I’d like to start with this important question, why is it essential for patients to play a role in their care and treatment decisions? 

Dr. Mark Schroeder:

Yeah, I mean patients are – a patient should be actively involved in decisions with their doctor. As a physician, doctors are thinking about “What is the best treatment for their disease or their cancer?” and patients, I think, have a role in trying to guide the doctor in terms of what outcomes they are seeking from treatment, what is there lifestyle like that we could potentially guide treatment around. Patients have different goals. Sometimes in cancer, we’re going for curative therapies. Sometimes we’re not, and quality of life is more important. Having an actively engaged patient ensures that your doctor is trying to tailor treatment to you.  

The patient who is educated also helps to bring resources to their physician about – sometimes physicians may not know of all the clinical trials that are ongoing or potentially even therapies. But have a patient ask about certain studies or ask about certain therapies, it helps to open a conversation with your physician to discuss those and to kind of talk through why it may or may not be a good idea for them in particular. 

Katherine Banwell:

Well, thank you. That helps guide us as we begin our conversation. As a patient, engaging in your care starts with understanding your diagnosis, so I’d like to go through some definitions. What is multiple myeloma? 

Dr. Mark Schroeder:

Multiple myeloma is a blood cancer. It’s a cancer in particular of a blood cell called a plasma cell. Everybody has normal plasma cells in their body. It’s part of your immune system that responds to infections; they are also cells that respond to vaccinations.  

And when a plasma cell becomes a cancer, it often forms a cancer called multiple myeloma. And that cancer results often times in damage to bones, low blood counts or anemia, potentially kidney problems, or possibly seeing high levels of calcium.  

Katherine Banwell:

What about smoldering myeloma? What is that? 

Dr. Mark Schroeder:

So, smoldering myeloma is a stage that happens prior to the development of myeloma that is causing organ damage. I talked about the damage to bones, kidneys, blood cells – that is called the CRAB criteria. The C stands for calcium, the R renal, A anemia, and B bones. We define myeloma by having damage to one of those four essential systems.  

Smoldering myeloma can happen when we actually see plasma cells that look like myeloma – that look like cancer cells, but they’re not causing the CRAB features of multiple myeloma. And there is a chance that sometimes that smoldering form of myeloma, it’s not causing any damage, but it can evolve and change into myeloma. 

Katherine Banwell:

What is MGUS?  

Dr. Mark Schroeder:

MGUS is a stage that happens prior to smoldering myeloma. We know that MGUS which stands for monoclonal gammopathy of undetermined significance – it’s a mouthful. That’s why we like to say MGUS.  

Katherine Banwell:

Yes. 

Dr. Mark Schroeder:

But it’s a protein that can be detected in your blood. Sometimes that protein does not mean you have a cancer. We can detect proteins like that in blood in patients who have, say, autoimmune diseases, and they’re at low levels. It’s just an immune response; it’s produced by those plasma cells that can be cancerous, but sometimes plasma cells grow because they’re stimulated – they’re overstimulated.  

And so, that monoclonal protein of MGUS can be detected in the blood, but we don’t see an increase in the number of cells in the bones that are classic for myeloma. But we know that about 1 percent of patients who have MGUS, every year, 1 percent might progress on to develop multiply myeloma. So, it’s a risk factor; it’s on the spectrum of disease from MGUS to smoldering myeloma to myeloma.  

Katherine Banwell:

Okay. And how is asymptomatic myeloma monitored?  

Dr. Mark Schroeder:

So, asymptomatic patients, I would consider those are the patients who have smoldering myeloma, so they don’t have the high calcium, the renal issues, anemia, or bone problems. And typically, those patients are followed up about every three to six months, depending on where they fit in kind of that spectrum of MGUS to smoldering myeloma to myeloma.  

Sometimes patients who have clinically identified myeloma and it presents very heterogeneous sometimes. They may not have a lot of organ involvement or organ damage, and maybe they’re frail, they’re elderly. And it may be appropriate also to observe patients who actually have some of the findings of myeloma, but the disease doesn’t seem to be as aggressive. 

Katherine Banwell:

Okay. Let’s talk about the different phases of therapy for myeloma, and I’m going to ask you for some more definitions. What is induction therapy? 

Dr. Mark Schroeder:

Induction therapy is the first treatment that we’re starting for myeloma. It’s oftentimes a combination of a number of chemotherapies that our goal is to get control of the cancer quickly, so reduce the burden of the cancer in a patient’s body.   

Oftentimes, when patients present with myeloma, that’s when the burden of cancer is the highest. So, induction therapy is a combination often of three or four different drugs given over the course of about three to four months to treat the myeloma and get initial control.  

Katherine Banwell:

What about consolidation therapy? What is that?  

Dr. Mark Schroeder:

So, after you have had a response to induction therapy, your oncologist might talk about, “Well, let’s deepen that response.” That’s when we think about consolidation. So, it’s going to be poten – most of the time is a change of therapy from the three or four drugs that you were treated for in the myeloma. An example of consolidation would be going through a stem cell transplant or more chemotherapy after stem cell transplant. So, that’s a change in therapy, and it ends up deepening the response, killing more of the cancer. 

Katherine Banwell:

And what about maintenance therapy?  

Dr. Mark Schroeder:

So, after you have gone through induction, you have control of the myeloma, we’ve deepened that response with consolidation, we know that myeloma is a cancer that tends to come back. And we know from experience that continuing some of the drugs that we used in induction at low doses are effective to try and prevent it from progressing or coming back, and it extends that period of time – and that’s maintenance therapy. It’s using some of the drugs we used to initially treat myeloma at lower doses to continue to suppress low levels of the cancer. 

Katherine Banwell:

Thank you for that. There are a number of treatments for myeloma patients. Can you talk about the types that are available? 

Dr. Mark Schroeder:

Yeah. So, the classes of – actually there is lots of drugs approved for treating myeloma but also recently approved.  

And we classify them into big categories. One of the categories is called immunomodulatory drugs – those are drugs like Revlimid and pomalidomide, or even thalidomide which was one of the first immunomodulatory drugs. Those are oral drugs that work on a specific pathway in the myeloma that leads to the myeloma cell dying. Another class of drugs are called proteasome inhibitors. Those include drugs like bortezomib or carfilzomib. Those drugs are often given under the skin or in the vein, and we know that they work really effectively on their own, but also when we combine them with an immunomodulatory drug like Revlimid or pomalidomide, the effect is even better. Another class is steroids. Steroids are kind of one of the first drugs used to treat this cancer, and steroids are effective at treating myeloma cells.   

Plasma cells are responsive to steroids. One of the first treatment regimens used to treat myeloma were traditional chemotherapies, and those are usually reserved for later on. You might think of traditional chemotherapy that causes hair loss, nausea, vomiting, low blood counts. Those, decades ago, were used to treat myeloma, but now we have effective oral, IV, or injection into the skin that don’t cause a lot of the traditional chemotherapy side effects but are very effective at treating the myeloma. And then another major class of drugs are considered immunotherapies. So, these are treatments that are engineered to either stimulate the immune system to go attack the myeloma, or maybe it’s even using part of your own immune system to engineer it to go attack the myeloma. 

Examples of those are called bispecific antibodies which kind of binds to the myeloma but binds to an immune cell, brings them together, or a CAR-T cell which takes your own T cells genetically modifies them to attack the cancer. 

Katherine Banwell:

And there is also a bone marrow transplant. Is that right? 

Dr. Mark Schroeder:

That’s right, yeah. I neglected – so, bone marrow transplant has been around for a while in myeloma. And despite it being around for so long and really good therapies being approved for myeloma, it’s still a standard treatment for myeloma. And bone marrow transplant in myeloma uses a traditional chemotherapy called melphalan that is associated with the chemotherapy side effects we talked about. But the advantage of bone marrow transplant is that it prolongs the time before the myeloma comes back and needs other treatments, and that’s why we do it. It can be toxic, but it can prolong the time before a patient needs another line of therapy.  

Katherine Banwell:

We know that everyone’s diagnosis is different. So, how do you determine a treatment plan for an individual patient? 

Dr. Mark Schroeder:

So, it depends in terms of the patient – initially, I will evaluate patients and determine how fit they are. Is it a patient that I think is strong enough to undergo a stem cell transplant? Is that going to be a benefit to them? That’s not necessarily a factor of just age, but it’s also, are they doing well functionally, or do they have any other medical problems like heart disease or kidney problems? Those things play into my decision on a treatment initially with patients. So, whether you’re fit or unfit will help to guide what your treatment is going to be in general. Fit patients are somebody that could undergo multiple treatments, go through a transplant, have minimal toxicity, and recover fully after more intensive treatments.  

Whereas, unfit may need more assistance, and we tend to reduce the intensity of treatments. It doesn’t mean the treatments, if you’re unfit, are less effective – they can be very effective. But our goals for treatment change in that situation. And we’re looking for responses but also looking for quality of life. And then it changes also depending on the genetics of the myeloma. Our treatment for patients who have genetic changes that are high risk will change compared to those that have what are called standard risk genetic changes.  

So, that is an important point to discuss with your oncologist if you have – Do I have standard risk or high-risk genetic changes in my cancer? And does that effect my treatment? And then also, treatment in somebody who is being treated a second time or third time or beyond for their myeloma depends on what treatments you had before and how effective they were.  

And what were your toxicities or side effects from those treatments? So, all those factors play into a decision of treatment for an individual.  

Katherine Banwell:

Oh, that’s great information. Let’s discuss what happens after treatment. How is the effectiveness of a treatment monitored? 

Dr. Mark Schroeder:

When you are initially diagnosed with myeloma, we will perform testing of blood. We look for that monoclonal protein or protein in the blood that is produced by the cancer cells. That protein level will be used to monitor the response of the cancer, and that’s a blood test – that’s called a serum protein electrophoresis. Also, initially, we’ll have x-rays of the bones, or it might be a CT scan or an MRI or PET scan that’s used to document if there is any bone damage. And oftentimes when we’re following up, we follow the bloodwork to look for reduction in that protein level.  

We may follow up additional x-rays to see if there are new areas in the bones that are damaged or if prior areas have responded to the treatment. And then oftentimes a bone marrow biopsy is used to document if you are in a complete remission which means that the protein we detected before or the cancer cells in the bone marrow cannot be detected after treatment. 

Katherine Banwell:

Why is it essential for patients to share any symptoms or issues they may be having with their healthcare team during and after treatment? 

Dr. Mark Schroeder:

Yeah, I mean, the treatments for multiple myeloma, they are typically continued in patients, and as we continue these treatments, side effects happen.  And as a physician, we can support patients through side effects. It may be as simple as adding a medicine to help with nausea. It may be modifying the dose of the treatments.  

So, it’s important to kind of monitor for things like, “I’m having a rash or diarrhea” or “I am getting nausea,” and letting us know right away. What the bad outcome would be if a patient is taking a medicine doesn’t let us know about side effects and decides to stop the medicine. Obviously, if you’re not taking a chemotherapy medicine, it’s not going to be effective to treat your cancer. That happens sometimes. So, having a good communication with your physician and your team of medical providers is important so that we can modify treatment. There are lots of alternatives for adjustments in the treatment that can be made that can be just as effective as the treatment you started on. 

Katherine Banwell:

So, communication is key. 

Dr. Mark Schroeder:

Yes. For sure, for sure. 

Katherine Banwell:

If treatment is successful, then when is a patient considered in remission? And what does remission mean? 

Dr. Mark Schroeder:

Remission – there are gradients on remission in myeloma. And we can have a partial remission which means we kill about half of the cancer cells. We can have very good partial remissions, or we can have complete remissions. And those equate to the depth of response or how well the myeloma responded. Those are measured by bloodwork, bone marrow biopsy, and may be repeat imaging or x-rays. So, if you have a complete remission, that means, we can’t detect that protein in the blood that was detected before, or protein that was detected in the urine, and we can’t detect the cancer cells on a bone marrow biopsy. We know that the deeper your remission or response to treatment, that equates typically with a longer time before the cancer may come back or need other therapies.   

Myeloma is a type of cancer that tends to come back, so we have very effective therapies, and sometimes, these therapies can get the myeloma to a state that we can’t detect one in a million cancer cells, but it tends to come back. And so, complete remissions means that, “Yes, it’s a good chance that the myeloma is not going to come back for years for you, but you still need to be monitored. You’re not necessarily cured of the cancer.” 

Katherine Banwell:

Unfortunately, relapse can occur after treatment as you’ve been talking about. And sometimes, a patient’s disease doesn’t respond to therapy, and that’s called refractory disease. What are the indicators that a patient’s disease may have relapsed?  

Dr. Mark Schroeder:

Yeah, so we would typically be following a patient about every three months. Somebody that has gone through the initial induction, consolidation, maybe they’re on maintenance therapy, or maybe they’re on active therapy for after they have relapsed from a myeloma. Each of those visits every three months, we are monitoring bloodwork, we’re monitoring the monoclonal protein that the myeloma produces.  

Or if it doesn’t produce much of that protein, we’re monitoring other parameters, so urine testing or maybe even imaging like a PET scan. And we’re looking for consistent rises in that number, and we’re looking for, not necessarily a little rise in the protein, but incremental continuous rise – that suggests that the myeloma is starting to grow again, and it’s growing on the current treatment, and we need to switch gears and try a different treatment. There are some patients who – that protein, the myeloma or the myeloma cancer doesn’t die to treatments – that’s refractory. So, we try a treatment, and there’s just no response. We don’t see a drop in the protein in the blood, we still see a good burden of the myeloma in the bone marrow biopsy. And those patients, that’s also an indication to try a different treatment.   

Katherine Banwell:

You mentioned that myeloma often returns, so how typical is it for a patient to relapse? 

Dr. Mark Schroeder:

Yeah, I would say that’s the norm for patients with myeloma. There are reports in patients who undergo things like stem cell transplant, that maybe 10 percent of patients might be out 10 years without detection of their myeloma, but that’s not the norm. So, most patients who are diagnosed with myeloma will go through periods of treatment and hopefully periods of remission – the majority go into periods of remission to myeloma where it’s not very active, but the myeloma tends to come back. 

Katherine Banwell:

If a person is relapsed or refractory, how are they typically treated? 

Dr. Mark Schroeder:

So, when they relapse, it depends on their prior treatment. So, if the myeloma is not responding to a drug, then it is, from the physician’s perspective that’s treating you, a good idea to change the type of chemotherapy drug that you’re on. Any time, whether it’s diagnosis or relapse, clinical trials are appropriate to engage with and potentially even use as primary treatment. All clinical studies in myeloma or for cancer in general are typically engineered around active treatments for the cancer. And so, those studies in myeloma when you’re having the cancer relapse, say, early in the course of your cancer, those studies typically are geared to use drugs that are approved by the FDA. Later in the lines of treatment, maybe you’ve had to progress after four lines of treatment, but trying to move them earlier, and they’re very active in the fourth line.  

So, you could potentially have access to an active treatment moved earlier in the treatment through a clinical trial. There is also a long list of other approved myeloma therapies. There is a good handout, I think, through the NCCN for patients for myeloma that lists a lot of the approved myeloma therapies and kind of guides patients. It’s a good resource book that I would point any of the listeners to. 

Katherine Banwell:

Oh, that’s a great idea. Thank you for that. What about emerging therapies for myeloma? What approaches are showing promise? 

Dr. Mark Schroeder:

So, I think the biggest news in myeloma, and across a lot of cancers now, are immunotherapies. We know in myeloma – now we have two CAR-T cells –  

Now a CAR-T cell is engineering your own immune cell called a T cell to express a receptor on its surface that binds to the myeloma, and then those immune cells go and kill the myeloma. That’s a form of immunotherapy.  

There’s two CAR-T cells for treating myeloma after the myeloma has come back four times, has needed four treatments. Those are very active in that line of therapy, and we can see response rates over 80 percent in patients who otherwise weren’t responding to other approved therapies for myeloma.  

On the other hand, there are other immunotherapies that are used earlier in the treatment course of myeloma. One that is not incorporated more frequently for the initial treatment is a drug called daratumumab – it’s an antibody. It’s a protein that binds to the surface of myeloma and stimulates the immune system to react against the myeloma. And so, it’s not a traditional chemotherapy, but it’s using your own immune system to attack the cancer.  

And then a third one that’s probably just as – it looks just as potentially effective as CAR-T cells are called bispecific antibodies. And that would use a protein similar to daratumumab which is an antibody, but it uses parts of antibodies to bind to – it could be two different proteins – one expressed on a T cell, the other one expressed on the myeloma cells. And when it binds, it brings those two cells together and causes your own immune system to attack the myeloma. Those are also very effective, and within the next month or two, there will be a bispecific antibody approved for treating patients with myeloma. 

Katherine Banwell:

Oh, that’s great news. Any others?  

Dr. Mark Schroeder:

Yeah, well – I mean, the other potential – there are other immune cells called natural killer cells that are also in clinical trials for development to attack myeloma, and potentially even engineering those natural killer cells to attack myeloma.  

There are other antibodies; sometimes the antibodies of protein bind a specific target on the surface of the myeloma. I mentioned one – daratumumab – but there is a whole list of others that are in clinical development. The one other antibody – or two, couple of other antibodies that are approved for treating myeloma are isatuximab which also binds to CD38. And another one called elotuzumab which binds to a protein called CS1 or SLAMF7 on the surface of myeloma.  

That’s more information than you probably wanted or needed, but those antibody therapies can be very effective in treating myeloma. There is another antibody therapy that has a payload of a toxin on the antibody, and it binds to BCMA or B-cell maturation antigen.  

That’s the same antigen that the bispecific antibodies as well as the CAR-T cells are targeting on myeloma surface, and so that is potentially one that is approved by the FDA also to treat myeloma.  

Katherine Banwell:

Okay. Let’s go to some audience questions. PEN community member, Mark, sent in this question prior to the program, “When is the right time for a clinical trial? When everything else is refractory?” 

Dr. Mark Schroeder:

No, I think clinical trials should be – you should engage your oncologist to talk about clinical trials right from the beginning. We typically think about clinical studies – they could be interventional where we’re actually giving a treatment. Some clinical trials are observational where we’re trying to learn about disease course in response to traditional therapies. Either of those may have direct benefit to the patient, or maybe it doesn’t affect the patient, but it affects future patients with myeloma.  

There are clinical studies like I mentioned that are moving therapies that are approved, but they’re approved after patients have been treated four or five times for their myeloma, and they’re now being moved earlier in the treatment. Some of those are at the initial treatment of myeloma in that induction phase. And so, we think that maybe by using some of these newer therapies or that immunotherapy class earlier on in the treatment of myeloma could result in deeper responses. We don’t know if it’s going to result in cures or that long remission beyond five or 10 years, but that’s the hope. If we can move the therapies earlier and prevent the cancer from becoming resistant to multiple treatments, maybe we can lead to longer remissions and longer survival of cancer patients. So, engage with your oncologist from the beginning through all of your treatment lines about clinical trials, is what I would say.  

Katherine Banwell:

Well, how can patients find out about clinical trials and what might be right for them? Where should they start?  

Dr. Mark Schroeder:

I mean, starting with your physician and having that conversation is a good start, but there are resources for patients. The Multiple Myeloma Research Foundation MMRF has good resources. There is a – called Myeloma Crowd that also has resources for patients with myeloma and social support for patients with myeloma to try to find and match you with a clinical trial. And then if you’re really academic and interested in doing your own homework online, all clinical studies in the United States, even internationally, are registered on a website called clinicaltrials.gov. Clinicaltrials.gov is – it can be searched, so you can search for myeloma; you can search for a specific drug.  

That will tell you, where are the studies being done, who are the study personnel, who should I contact to find out about the study? Unfortunately, not everybody can travel for treatment for their myeloma, and the best chance of potentially participating in a research study is to initially talk with your oncologist about it. There may be a larger center nearby that you can visit to consider clinical trials.  

Clinical trials that are trying to use the new immunotherapies would be a great option, but they may not be offered in, say, a community oncology practice. You have to have the infrastructure to conduct those studies. And if you have the resources to be able to travel, then finding something on clinicaltrials.gov and – I’ve had patients do the legwork and talk with their local oncologist and get referred to a center that actually has a study that they’re interested in participating.  

But a lot of times, studies are going to have you visit the center for all the screening tests and all the procedures for study. 

Katherine Banwell:

Right, so you have to know that you have the time available as well as the resources. 

Dr. Mark Schroeder:

Right, and the resources to do it. Yeah.  

Katherine Banwell:

Yeah. Trevor had this question, Dr. Schroeder, “My myeloma is considered high-risk. What treatment options are available to me, and are there clinical trials specifically for high-risk disease?” 

Dr. Mark Schroeder:

Yeah, great question. High-risk myeloma happens in about a quarter of patients, so one in four patients will have high-risk myeloma at the diagnosis. And it’s important because we know that when we say high-risk, that means that the myeloma is going to potentially come back sooner after treatments. It doesn’t mean that the treatment you’re going to be given is less effective, but it has a high propensity to come back sooner.  

Those patients with high-risk myeloma still benefit from a lot of treatments that we have for myeloma, but there are clinical trials geared to try and increase treatment in patients with high-risk myeloma to try to change the fact that their cancer comes back sooner than somebody who doesn’t have the high-risk features by using a novel chemotherapies or novel drugs to try to improve responses. So, there are for sure clinical studies, either at – potentially at initial diagnosis or at the time of relapse that could be entertained for patients with high-risk myeloma. And I would encourage you to seek those out for sure.  

Katherine Banwell:

Yeah. Great. Thank you. And please continue to send in your questions to questions@powerfulpatients.org, and we’ll work to get them answered on future programs. As we close out our conversation, Dr. Shroeder, I wanted to get your take on the future of myeloma. What makes you hopeful? 

Dr. Mark Schroeder:

Well, I am hopeful – just within the last five years, there have been a number of new drugs approved for myeloma. They are approved for later lines of therapy, but they are being moved earlier in the treatment. And within the last 10-20 years, we’ve seen an improvement in the survival of patients with myeloma. As these new therapies are in development, as they’re being moved earlier in the treatment line, I’m very hopeful that survival and potentially cure for this cancer is possible. The only way that we’re going to get to that point is through clinical research and for patients to partner with their physicians and to consider clinical trials because that is the only way that new drugs get approved and are available to other patients with myeloma. So, I’m excited about what is approved; I’m excited about what’s coming through the pipeline to treat myeloma.  

Katherine Banwell:

Dr. Schroeder, thank you so much for taking the time to join us today. 

Dr. Mark Schroeder:

You’re welcome, Katherine. It was a pleasure.  

Katherine Banwell:

And thank you for 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 today. 

What Do DLBCL Patients Need to Know About Treatment and Research?

What Do DLBCL Patients Need to Know About Treatment and Research? from Patient Empowerment Network on Vimeo.

How have diffuse large B-cell lymphoma (DLBCL) treatment options evolved? Lymphoma expert Dr. Matthew Matasar reviews current treatment options for DLBCL and shares his perspective on where research is heading.

Dr. Matthew Matasar is a lymphoma expert at Rutgers Cancer Institute. To learn more about Dr. Matasar, visit here.

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Transcript:

Katherine Banwell:

Dr. Matasar, what are the types of treatments currently available to treat DLBCL? 

Dr. Matasar:

So, DLBCL, or diffuse large B-cell lymphoma, is the most common type of aggressive B-cell non-Hodgkin’s lymphoma in America and really around the world. Aggressive lymphomas are a double-edged sword. They tend to grow quickly over weeks to months, and they tend to make people feel sick if left untreated, but they’re potentially curable in many although not all patients.  

We now have a growing body of treatment options available to maximize the changes of cure and to minimize short and long-term risks in patients diagnosed with aggressive B-cell lymphomas.  

The first recent innovation is a treatment program that seems to improve upon the standard of care treatment called R-CHOP, R-C-H-O-P, which is a combination of chemotherapy and immunotherapies in the treatment of newly diagnosed diffuse large B-cell lymphoma. And this new regimen substitutes out one of those medicines, the O, which is a medicine called Oncovin, or vincristine, with a newer medicine that has a long name called polatuzumab vedotin, or pola for short. And we found in the recent Polarix trial was that by introducing this new pola medicine instead of the older Oncovin treatment, we’re able to lead to longer durations of remission for patients with newly diagnosed large cell lymphoma and is able to do so without any increase in short- or long-term side effects, which makes it a real win in my mind.  

That’s one major innovation. The second is in patients who, unfortunately, have a relapse of their diffuse large B-cell lymphoma or whose disease does not go into remission after first treatments. We now know that patients who have an early relapse or have, what we call, primary refractory disease, meaning it didn’t go away after the first treatment at all, is we now have data using treatments that are calling CAR-T cell, or chimeric antigen receptor modified T-cell therapy. CAR-T cell therapy is a treatment in which we use your own body’s healthy T cells. Some of those are filtered out, and they are genetically re-engineered in way that trains them to attack lymphoma cells and then given back as a living treatment, as a mini-transfusion.  

This CAR T-cell therapy was compared to a standard chemotherapy program that uses high dose therapy with stem-cell rescue or auto transplant, or stem cell transplants, for patients with this high-risk scenario, early relapse or primary refractory disease. 

And what we found is that CAR T-cell therapy with either the treatment called axi-cel (Yescarta) or the treatment called liso-cel (Breyanzi),two different CAR-T therapies, were superior to the traditional chemotherapy and stem-cell transplant approach in these highest risk patients leading to marked improvements in outcomes in these patients and maybe even improving overall survival, which is a very high benchmark at this early time point in these two critical trials. So, improvements in newly diagnosed therapy and improvements for those patients who suffer early relapse or primary refractory disease mark two important advances in the care of patients with DLBCL.  

Katherine Banwell:

What are you excited about when it comes to DLBCL treatment and research?  

Dr. Matasar:

What I’m most excited about is our ability to improve outcomes in the highest risk patients. We often talk in academic circles about unmet need, which is just a silly way of saying we really wish we could do better. And there’s unmet need across the line when we think about how we take care of patients with aggressive B-cell lymphoma, newly diagnosed patients, patients who are newly diagnosed who may be older or more frail, who may need specialized treatment approaches, patients who suffer a relapse of this disease one or multiple times.  

We cure many patients with diffuse large B-cell lymphoma, but many is not enough. And we’re not going to rest until we can have uniform and universal success and, unfortunately, we’re not there. But we’re working to get there day after day. The options are expanding. The trials are promising. Novel therapies are very exciting, and I really believe that these next years are going to see profound innovation and improvements in outcomes. That comes with clinical research and with patients being willing to trust doctors to participate in this journey together and doctors being willing to take a chance and offer patients novel therapies when we know that our current treatments are simply inadequate. 

How Do Test Results Impact Myeloma Treatment Options?

How Do Test Results Impact Myeloma Treatment Options?  from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Melissa Alsina reviews the test results that are taken into consideration when choosing a treatment approach for patients.

Dr. Melissa Alsina is an associate professor of medicine in the Blood and Marrow Transplant Program at Moffitt Cancer Center in Tampa, Florida where she also serves as head of the Multiple Myeloma Transplant Program. Learn more about Dr. Alsina, here.

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Transcript:

Katherine:

We know that patients undergo testing when diagnosed. How do test results affect treatment choices? 

Dr. Alsina:

So, in general, we do a bone marrow, we check for the genetics of the myeloma cells, see what are the genes that are affected in the myeloma cells, and that helps us define myeloma as high-risk or standard-risk, and that can help us decide what treatment we want to give these patients. Unfortunately, it’s not totally well defined. 

I wish we could use that in a better way and there are drugs that could really target, but there is some information. We know, for example, that proteasome inhibitors are important for patients with high-risk myeloma, so we definitely try to include that in a patient that is high-risk, and the other thing is that patients that are high-risk, it’s even more important to get to that remission, so we’re going to push treatment to get there, treat these patients a little bit more aggressively. 

Other than that, depending on, for example, what are the blood counts – some patients have a lot of bone marrow involvement and their blood counts are very low. This is not common, but it happens, and so, when that happens, we might be more aggressive up front and give these patients more aggressive chemotherapy to clean the bone marrow before changing them to the more normal therapies because the treatments that we give, like Revlimid (lenalidomide), Velcade (bortezomib), Darzalex (daratumumab) can depress the counts, right? 

So we’re in that battle. The patients already have low counts, we give the treatment, the treatment lowers the counts further, so it’s hard to give these treatments in these settings. And then, the third thing that we take into account is kidneys. About 25 percent of the patients will have renal insufficiency when they are diagnosed. Some of these drugs, particularly the immunomodulatory drugs like the Revlimid are metabolizing the kidneys, so it’s very hard to dose these drugs when the patients have renal insufficiency. 

So sometimes, for these patients, we avoid the IMiDs up front. We give a different combination until the disease gets better, and then we introduce the IMiDs. We think these immunomodulatory drugs like Revlimid are super important in the treatment of myeloma, so we want to give them, but sometimes we have to delay starting them until the patient’s kidney function improves.