Tag Archive for: myeloma relapse

PODCAST: Myeloma Patient Expert Q&A: Dr. Sikander Ailawadhi

 

 
In this START HERE myeloma program, Dr. Sikander Ailawadhi from Mayo Clinic spotlights priorities in the rapidly expanding myeloma treatment landscape. Watch as Dr. Ailawadhi addresses pressing questions submitted by patients and families, providing invaluable guidance and reassurance in navigating the complexities of myeloma care.

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Transcript:

Lisa Hatifield:

Hello and welcome. My name is Lisa Hatfield, your host for this Patient Empowerment Network START HERE program, where we bridge the expert and patient voice to enable you and me to feel comfortable asking questions of our healthcare teams. The world is complicated, but understanding your multiple myeloma doesn’t have to be. The goal is to create actionable pathways for getting the most out of myeloma treatment and survivorship.

Joining me today is Dr. Ailawadhi, back by popular demand. Dr. Ailawadhi is a respected multiple myeloma expert from Mayo Clinic. Dr. Ailawadhi’s career focus includes the treatment of plasma cell disorders like myeloma and understanding the epidemiology and pathophysiology of this disorder. It’s always such a pleasure having you, Dr. Ailawadhi. I’m really excited you’re joining us again. So thank you for joining us.

Dr. Sikander Ailawadhi:

And thanks a lot for having me, Lisa. This is excellent. I look forward to this next iteration of the Patient Empowerment Network START HERE program.

Lisa Hatfield:

Thank you. So before we dive into today’s discussion, please take a moment to download the program resource guide using the QR code. This guide contains pertinent information to guide you both before and after the program. And this program will provide you with a comprehensive update on the latest myeloma news and its implications for you and your family. Following that, we’ll launch into some questions that we have received from you.

So let’s start here. Dr. Ailawadhi, at this juncture in myeloma history, we are witnessing unprecedented activity, a surge of new treatment options, and a wealth of insights. Today, we are privileged to have your expertise to help us decipher these developments and shed light on the advancements shaping the landscape of myeloma care. First, we’re going to get a high-level update from Dr. Ailawadhi on what the latest myeloma news means for you and your family. And then we’re going to talk about some questions that you’ve sent in. So let’s get started with the high-level update, Dr. Ailawadhi. Can you speak to the latest news and priorities in the rapidly expanding myeloma treatment landscape?

Dr. Sikander Ailawadhi:

Excellent. I think, Lisa, that’s an excellent and important question. Because as you rightly mentioned, there is such a large amount of data that is coming through for myeloma all the time. I mean, it’s almost, we kind of talk about the fact that every time you turn your shoulder or look over your shoulder, there is a new drug approved. So I can imagine this can be very overwhelming. So what I’ll say is that in my opinion, there are some categories of new data that are pertinent and important for our patients. 

The two or three out of them that come to my mind, one is what’s called CELMoDs, or there are a couple of agents there called iberdomide, mezigdomide. These are showing some interesting data. Important to keep in mind that they are somewhat related to the immunomodulatory drugs lenalidomide (Revlimid), pomalidomide (Pomalyst), but they’re showing benefit in patients who have had len and pom before and have progressed. So exciting stuff there.

We’re also seeing some interesting data about newer CAR Ts and bispecific antibodies. They are all coming up with some benefits in some cases. I think it’s important to keep in mind that the bispecifics are landing at the 60 to 70 percent response rate, and CAR Ts are typically landing at the 80 to 90 percent response rate, but there are more agents expected.

There are also some newer bispecifics in different classes, like one of them is called cevostamab, which is an FcRH5 inhibitor or targeting bispecific. So newer bispecific, not just more of the same category. And there has also been recent data about Bcl-2 inhibitors, which have been traditionally used for patients with translocation 11;14.

There have been some negative data, negative as in trials, which did not pan out with a drug called venetoclax (Venclexta), but there are two other drugs that had some recent data shown from different companies, which were exciting information. So in my mind, those are kind of the broad new drug categories. There is another, a couple of other quick things that I’ll mention.

One is we’re getting more and more information about real world experience with these new drugs. It’s good to see that CAR Ts are panning out very similar in the real world as they are in clinical trials. We’re also seeing that the side effect profile of a lot of these newer novel immunotherapy drugs is similar as seen in the clinical trials.

Racial ethnic disparities are something which are very close to my heart, and there is more and more information coming out in that. Unfortunately, highlighting the disparities more still rather than yet coming up with solutions. And I think the last thing that I feel which has been recent has been at the American Society of Hematology meeting in 2023, which was in December in San Diego.

One of the myeloma studies actually became a plenary session presentation, which is a pretty big deal for any disease area. So one thing is that it gets highlighted. Secondly, it was a combination of a regimen called isatuximab-irfc (Sarclisa) with carfilzomib (Kyprolis), lenalidomide, and dexamethasone (Decadron) in newly diagnosed patients.

It’s a randomized trial, Phase III, which was presented. I think the important part is we saw unprecedented deep responses and patients in much, much higher numbers than before becoming MRD-negative. So very deep responses. So these are kind of some very broad, but lots of highlights that I talked about.

Lisa Hatfield:  

All right. Thank you. So can you also talk about some of the newer tools for myeloma progression and relapse and what patients might want to know about that? And in particular, maybe talk a bit about MRD testing and the role of MRD testing for patients who relapse.

Dr. Sikander Ailawadhi:

Excellent question. Lisa, I think the first and foremost thing an important part for our patients to learn is what are their “tumor markers,” for the, or disease markers for myeloma. We can follow myeloma by either the M spike or monoclonal protein, by light chains, by monoclonal protein in the urine or blood. And it’s important to keep that in mind because every now and then we’ll see patients who say, Hey, my ratio changed. So I’m progressing. Well, that comes after the light chains change. So it’s important to understand the role of these things.

So M spike in the urine, M spike in the serum and light chains. One of them is typically the marker for a patient. Now the MRD status or minimal residual disease that is looking for one cell, one myeloma cell from amongst 100,000 cells in the bone marrow. So it is looking at a very deep level. The most important benefit of MRD testing right now is to understand that if a patient turns MRD negative, then they have a superior outcome. Their prognosis is better. Their progression free survival, or the time before their disease comes back is longer. 

But when a patient is MRD-negative and is being followed or maintenance or whatever, if the bone marrow turns MRD-positive, then that might be the sign that the disease might be coming back. Right now, we do not keep switching drugs to get to MRD-negative. That is not the goal of treatment. The way to think about it is we want to get to MRD-negative, but that means it’s incumbent upon us to try and pick a regimen that is more likely to get to MRD-negative. That’s the way to think about it.

Let’s pick a regimen more likely to get us into MRD-negative and hope that we get to MRD-negative. We see every now and then that the patients keep switching regimens just to get to MRD-negative. That’s not the way to go because you’re just using up options too quickly, too fast. A common question that patients ask is, well, does that mean I need to get annual bone marrow biopsies and MRD testing? Probably not.

That’s too much testing. So what I suggest is that once somebody has turned MRD-negative, it’s important to keep an eye on every single thing. Now, change in any of the routine labs, imaging, new symptoms, etcetera. That’s when we switch to the bone marrow again and see if the patient has turned MRD-positive. There are clinical trials going on right now which are stopping drugs based on repeat MRD negativity or starting drugs on MRD positivity. But those are clinical trial questions.

Lisa Hatfield:

Okay. Thank you for that. So along those same lines, since you’re a Mayo physician, I’m curious about the mass spec testing. So if a patient say has been MRD-negative for some time, still wants to monitor at a deeper level, even though it’s not commercialized yet, do you see a role for mass spec testing on a regular basis in the future and being rolled out to community facilities also?

Dr. Sikander Ailawadhi:

Absolutely, Lisa. I did not specifically bring it up because mass spec is not, like you rightly said, is not yet commercially available. Now we’re doing mass spec quite frequently at Mayo Clinic. Basically mass spec is taking up a blood sample. Important to keep in mind, it’s not a bone marrow test, it’s a blood test, but it looks for those abnormal proteins based on the protein weight at a much, much lower level. Our SPEP or serum protein electrophoresis does not pick up very small quantities of the protein mass spec does. So in an essence, the mass spec, if somebody is negative on that, turning mass spec negative to mass spec positive may be an earlier sign of the disease coming back rather than the SPEP yet turning positive. But as you rightly said, it is not yet commercially available. I do see the benefit of it.

There is more and more data coming in favor of it, and there was data that was also at ASH. So I do see that in the future we’ll be able to most likely have it available more widely. At this point, it is just a blood test to attempt to check the disease level at a much deeper level and be able to notice if the disease is progressing sooner than our currently available tools.

Lisa Hatfield:

Great. Thank you. And as a patient, I like to have one more data point that they can get from my blood, not from my bone marrow to assess the disease. So thank you for explaining that. Regarding survivorship, patients are living longer with myeloma in general because of the novel therapies that have come out in the past few years. So how is myeloma survivorship evolving, and what’s different now than it was five or 10 years ago in terms of treatment planning?

Dr. Sikander Ailawadhi:

Yeah, I think it’s very important to keep that in mind. When I see a newly diagnosed patient, I’m not just telling them, “Hey, this is your induction therapy, and your transplant is the goal.’ We’re trying our best to decide that patient’s life journey with myeloma over the next 10, 15 and hopefully more years. So we’re trying to pick and choose the regimen that is most likely going to help the patient the most today and most likely will give a longer duration of the response. So when you say survivorship, that also very importantly brings up the point that patients are living with myeloma longer. We have to manage their health overall. So looking for any side effects from treatment, managing them very well so the patient is able to stay on the treatment and maintain good quality of life.

There are actually, are clinical trials looking at stopping treatment when there is a very deep, prolonged response. Again, going towards survivorship and giving the patient’s quality of life. There is looking for other cancers. In fact, I had a patient in the clinic and we were talking about just myeloma in general and I was telling them, “Okay, please remember you may not want to do a colonoscopy, but you already have one myeloma cancer diagnosis. The risk of subsequent cancers is always there in any cancer patient.” So that was a male person. So I said, “Okay, please do not miss your colonoscopy. Please do not miss your prostate screening and whatever is age-appropriate must be done.” So managing everything because myeloma is not a sprint, it’s a marathon.

We want to make sure that we pace ourselves well so we manage all the symptoms, all the signs. Bone health becomes much, much more important because the same bone structure is now going to carry us longer and many more years. And as you rightly said, planning, which treatment comes first, which comes next, when does CAR T come? It’s not that everybody must get CAR T today. That’s not the answer. So what to use when becomes extremely more important.

Lisa Hatfield:

Thank you for that. And thank you, Dr. Ailawadhi, for that important reminder. All of you watching, get your regular screenings, like he said, prostate cancer, mammograms, colonoscopies, get it done. So thank you for that.

One of the things that comes up with that regular, not regular screening, but monitoring after certain therapies for future malignancies, there’s been some discussions about post-CAR T, particularly with T-cell malignancies and monitoring for that. Can you just give a little description of that and any concerns that you have with that or any encouragement you have regarding that and whether that weighs into your treatment options that you give to patients when they are asking about CAR T therapy?

Dr. Sikander Ailawadhi:

Absolutely. Extremely important question, Lisa. This really had a lot of discussion going on. It’s been going on for the past few months now. Okay. So first let’s explain the landscape. The FDA reviewed CAR T-cell treatment because of the fact that there were about 19 T-cell malignancies noted in several thousand patients.

Out of those 19 cases of T-cell malignancies, there was one case of multiple myeloma to the best of my knowledge. Now, risk of subsequent cancers is something, unfortunately, every cancer patient lives with, but in myeloma, we have known about that, especially from our historical knowledge of second malignancies with lenalidomide-based maintenance therapy post-transplant. So subsequent malignancies have always been a risk. There is some risk that is being talked about with CAR T, but frankly speaking, the way I look at it, the risk is significantly lesser than the potential benefit.

Because remember when these CAR T therapies, the two agents got approved in myeloma, they were approved in a situation that there was no standard therapy. And we saw somewhere about 70, 75 percent response rate with one of them and about 98 percent response rate with the other one. So in a setting where there was nothing, you can see the degree of benefit. And the risk of second malignancies is relatively small. So we must discuss this.

A patient must be aware of it, but I think the benefit is way more than the risk. So we document, we discuss, we have specific documentation that we do and specific information that we share with patients, but I think still the benefit is significantly more than the risk.

Lisa Hatfield:

Great. Thank you so much for explaining that. And for any of you out there watching this, Dr. Ailawadhi is a myeloma specialist, and I highly encourage anybody who is looking at CAR T therapy or even for a first consult for myeloma, seek out even one consult from a myeloma specialist. It is so important in trying to understand these therapies and any fears you may have regarding those therapies and the risks of that. So really appreciate that, Dr. Ailawadhi. Thank you. So I think it’s time now to start answering questions from patients that we received from all of you in the audience.

Please remember, this is not a substitute for medical care. Always consult with your medical team. And we are going to jump right in, Dr. Ailawadhi. We have a lot of questions from patients here and I’ll just start with the first one. This patient is asking, my M spike keeps rising in spite of chemo. What can I do?

Dr. Sikander Ailawadhi:

Very important question, Lisa. Every patient must understand what their disease marker is. This patient is asking about the M spike, which is the monoclonal spike, whether it’s in the blood or in the urine. And if the M spike is continuing to increase and there is a significant increase, significant is defined by at least 25 percent from the nadir or from the bottom most point with the, at least a absolute increase of 0.5 gram per deciliter. So half a gram per deciliter. So we want a 25 percent increase, but we also want at least 0.5 gram per deciliter.

So if somebody had an M spike of one at their best point, then the increase to 1.5 is significant. If somebody had the M spike of 0.2, then it’s not the 25 percent increase, it’s the 0.5 that must happen. So they hit 0.7 and that’s a significant increase. So that’s how we think about M spike, 25 percent with an absolute of at least 0.5 gram per deciliter.

If that is indeed happening, this would be considered a biochemical progression. And at that point, it should be considered to switch around the treatment because we don’t want the disease to grow to the point that there are actually symptoms showing up or organ damage happening. We want to be able to capture the disease progression sooner and act upon it.

Lisa Hatfield:

Great, thank you. Do you have any recommendations for people who, as we might have some patients watching this, who are light chain only? Any guidelines on if those numbers are rising?

Dr. Sikander Ailawadhi:

That’s an excellent question too. So if somebody has light chains as their marker, we are looking at an increase in the involved serum free light chain. So if somebody has kappa as their marker, the kappa is going up, or if they have lambda as the marker, the lambda is going up. Typically, if both of them go up, that is not disease progression. That could be coming from kidney dysfunction. Somebody is dehydrated and they get labs checked. Both kappa and lambda might be elevated. Again, a 25 percent increase in the absolute. But at the same time, we are also looking at at least 10 milligram per deciliter change.

So if somebody had a light chain of two milligram per deciliter, if it goes to 12, that might be a significant change. But I can say that light chains are a little bit more volatile and they do get affected by our fluid status. So if I ever notice a patient with a light chain increase, I’m more likely to repeat the test very soon, maybe even at a couple of days, one week interval, just to make sure that there is a trend rather than just a fluctuating light chain.

Lisa Hatfield:

Okay. Thank you for that information.

Dr. Sikander Ailawadhi:

And I should maybe, very quickly add, we do not check light chains in the urine. Light chains should be checked in the blood. Urine light chains are very nonspecific and there’s no need to test them.

Lisa Hatfield:

Okay. That’s helpful also. So patients don’t have to walk around with their big orange jugs full of fluids. So thank you. All right. This might be a complicated question to answer. But in general terms, for those who relapse for the first time, what are the best treatment options?

Dr. Sikander Ailawadhi:

I think that’s a very important, and I can imagine a scary situation. So somebody who relapses in general, not just even the first time, the factors that are taken into account for deciding what treatment they should get, there are broadly three categories of factors. Patient factors deciding what’s the age, what’s the other comorbidities, are they diabetic, are they heart disease, kidney dysfunction, because those things go into the decision of what may or may not be given. So patient factors.

Also importantly, how close are you to your treatment center? Can you come in for infusion or injection drugs time? And again, can you prefer or do you prefer oral drugs only? Et cetera. Those things become important. Then that…so that’s patient factors and disease factors. How fast is the progression? Is it high-risk disease, standard risk disease? Is it biochemical progression like the previous person asked?

Or is it actually a clinical progression in which there’s kidney dysfunction or anemia or bone disease? Because the choices and the urgency of treatment may change. So patient factors, disease factors, and then drug factors are the third class or third category, which is what have you had before? How long have you been on it? Are you on maintenance or not? Is your disease considered refractory to a certain agent, meaning resistant to a certain agent? Typically, if you were on a treatment and your disease is progressing, that same drug may not be used again.

And there are some times that we will reuse a drug, but generally not. We can use the same class, but we may not typically use the same drug. So I think the choice of treatment depends on all of those factors put in. And then we come up with one or two or three regimens and we discuss them with patients. And, of course, being an academic, physician, I must say there is always, you must always seek out good clinical trials if they’re available to you. That is the way our field moves forward.

Lisa Hatfield:

Yes, thank you for that information. So we have another patient asking, “Do myeloma patients require multiple prior therapies prior to being eligible for CAR T?” And what’s the rationale for not implementing CAR T immediately, which probably has to do with FDA approval based on clinical trials at this point?

Dr. Sikander Ailawadhi:

Absolutely. You’re absolutely right, Lisa. So any drug, let alone CAR T, any drug can only be given in the situation that it is approved by the FDA. So basically in accordance with that drug’s FDA approval label. Currently, CAR T-cell therapy is approved in the U.S. after at least four prior lines of therapy. And the patient must have had treatment with at least one proteasome inhibitor,  for which we have three drugs, bortezomib (Velcade), ixazomib (Ninlaro), and carfilzomib. They must have been treated with at least one prior immunomodulatory drug; lenalidomide, thalidomide (Thalomid), pomalidomide. And they must have been previously treated by at least one monoclonal antibody, daratumumab (Darzalex) or Isatuximab (Sarclisa).

Once the patient has had all these criteria met, they’ve become a candidate for CAR T-cell therapy. Frankly, we cannot just use a drug anywhere because we cannot use a drug where it has not shown to be of benefit. And importantly, it has not shown to be of any risk. So CAR T-cell therapy in the first line setting is being studied in clinical trials, but is not FDA-approved. Currently approved only after four prior lines, but the FDA is reviewing data for both the CAR T’s to see if they may be available sooner. As of right now, that approval is still pending.

Lisa Hatfield:

Okay, thank you. We’re hopeful that that will happen soon.

Dr. Sikander Ailawadhi:

Hopeful.

Lisa Hatfield:

Yeah. So interesting question from a patient, “Does CAR-T therapy actually change one’s DNA?”

Dr. Sikander Ailawadhi:

No. The CAR T therapy does not change one’s DNA. What happens is, there are T cells taken out of a patient. The DNA of those T cells is modified and then those T cells are given back to the patient. Those T cells do not go and integrate into your other healthy body cells or your stem cells, et cetera. Those T cells, it’s almost like giving a boost of immunity, which is targeted against your myeloma. So those T cells go in and they fill those myeloma cells. Now we hope that those T cells perpetuate and teach or create some memory T cells and that immunity lasts a little bit longer. But all of that genetic modification stays within the T cells. It does not integrate anywhere else.

Now, I know there was a previous question about T-cell lymphomas, that is related to this question in a way because the risk that is theoretical is, that that genetic modification in the T cells might make those T cells replicate uncontrollably leading to a T-cell cancer or T-cell lymphoma. But I’m saying that this is theoretical because while it is possible, it happens extremely rarely and even in the cases where the cancer happened, it has been seen that the cancer may not come from that portion of the DNA that was…that’s where the modification was done. So, low risk.

Lisa Hatfield:

Okay. Thank you very much for that.

Lisa Hatfield:

Okay. So what would be the next steps, Dr. Ailawadhi for a patient who’s had CAR T and reaches a relapse state or is relapsed?

Dr. Sikander Ailawadhi:

Yep. This is something, unfortunately is the truth of the matter in myeloma at least that we are, we don’t seek cures. We have had some long remissions. I have, for example, patients who are now reaching three, three-and-a-half years of remission on CAR T treatment who received it on clinical trials even before they got FDA-approved.

But, unfortunately, the disease does come back. So what happens is, we are seeing data that the novel, other novel immunotherapies like bispecific antibodies, even the ones who go after the same target as CAR T, BCMA targeting bispecifics, they do have some response rates, good response rates in post CAR T setting. So the bispecific antibodies by themselves may give us 60 to 65 percent response, but in the post CAR T setting, that response might go down to 40, 45 percent. So less responses, but still possible.

There are also bispecific antibody. There is one available, which is not against BCMA, it is against GPRC5D. That’s a bispecific called talquetamab-tgvs (Talvey). So a novel target. There is…there are of course a lot of clinical trials. There are some clinical trials that are even looking at CAR T post-CAR T. So different kind of a CAR T. Those clinical trials are going out. So what I would suggest is that if your disease progresses after CAR T-cell treatment, you should very strongly consider getting to a specialist myeloma center and get an opinion like you mentioned, Lisa.

That is so important because the choice of treatment is extremely important at that time. And we are trying our best to sequence all the options we have, in a way, actually one of my patients mentioned, one of these days, Hey, does that mean that I’m basically buying time till something new and exciting comes along? And I said in a way that is true. That we are trying to stretch all our treatments and get to the point that something new and promising just like CAR T comes, and hopefully we get longer benefits again.

Lisa Hatfield:

Thank you for that. So when you say there’s a possibility of CAR T and then a post-CAR T maybe a second CAR T. Would that be a different target then?

Dr. Sikander Ailawadhi:

So there could be a different target. I have, in fact, just yesterday I saw a patient who had received one CAR T in a clinical trial and then they were subsequently able to receive a CAR T standard of care, which had been FDA approved. So they used different CAR Ts, but one was in clinical trials and one was standard of care.

Lisa Hatfield:

Oh, great. Okay. Again, important to see a myeloma specialist to tease out all this information. Thank you. All right. This patient is asking, “I’m 81 and living with comorbidities. The myeloma was diagnosed after bone marrow test. How is treatment fitness determined?” And also a question about that is if you’re given an ECOG status of something you don’t like it, can that be improved after you’ve had treatment?

Dr. Sikander Ailawadhi:

Absolutely.

Lisa Hatfield:

Maybe be eligible for a trial or something.

Dr. Sikander Ailawadhi:

Correct. Correct. That is so important. When this patient mentioned that they’re 81-year-old and they’re living with comorbidities, I think, so when I’m talking to a patient who’s new to me, it’s very important for me to try to tease out what was their performance status or their fitness status prior to myeloma. Because my goal is to try to get them as close to that as possible. Now if this patient is saying that they were already quite frail before the diagnosis of myeloma and myeloma is added to the frailty, then it becomes a little tricky because we’re starting in a difficult spot. We do determine fitness by asking questions, simple questions like, what can a patient do at baseline? Can they do grocery store or grocery shopping by themselves? Can they walk around the block? Do they get short of breath? Et cetera.

And frankly, there are 81-year-olds who are playing golf every day and are fitter than me. So I’m just saying that age by itself is not the criteria. And, Lisa, like you rightly mentioned, if there are fitness issues coming from the disease itself, then that’s the time that we actually have to work with the treatment, get the treatment started, and then assess the fitness a couple of months later, a couple of cycles later. Because the treatment may have worked and may have improved the fitness quite a bit.

Lisa Hatfield:

Great thank you for that. So this person is asking, their husband is starting maintenance therapy, so I am assuming they just finished induction therapy, having leg pains mostly at night. Could this be a form of peripheral neuropathy or is maybe from bisphosphonates or from any of the medications that maybe were used during induction?

Dr. Sikander Ailawadhi:

So, excellent question. So, this is almost going back to that survivorship question that we discussed earlier, that it’s so important to manage the side effects and maintain quality of life. So, a lot of patients with myeloma will say that I have cramping or symptoms or some pins and needles at night more so. Part of it is because body’s at rest, relaxed, things, symptoms become more focused. Yes, it could be peripheral neuropathy, but at the same time certain drugs caused muscle cramping or what’s called myalgias, sometimes maintenance therapies can cause that.

It’s important for somebody to be able to determine is it coming from muscles or nerves? Is it coming because some electrolytes are abnormal. Like one of the common things is low magnesium or low potassium can cause neuropathy, for example, or cramping. I’ve had patients who will get some over-the-counter lotions or some forms et cetera, which are infused with some electrolytes and say that they feel some benefit. So topical things are good. So I think it’s important to figure out is it muscle or nerve and is it coming from drugs or disease? And that’s where your physician can help tease it out.

Lisa Hatfield:

Okay, thank you. So we have a patient who is talking about her genetic abnormalities, but has been through both auto and allo stem cell transplant in the last two years and has relapsed. And is asking, “Can CAR T-cell therapy help me?” And would she even be eligible for CAR T therapy given the allotransplant?

Dr. Sikander Ailawadhi:

That’s an important question. So first of all, sorry to hear that, that your disease is behaving that aggressively, that you’ve had both the transplants in the past two years and still having issues. So yes, CAR T can still be used after an allotransplant. There are some criteria. You should not be on any graft versus host suppressive medications, and you should not have any active graft versus host disease going on. So depending on those, yes patients can get CAR T post. And, in fact, I’ve had a couple of patients who’ve had CAR T after allotransplant.

Lisa Hatfield:

Great, thank you. I’m sure that’ll give this patient some hope. Are there any studies showing that treatment can be tapered? Tapered to by daily, once 90 percent reduction in myeloma has occurred with various therapies. So in general, you may know what medication this patient’s talking about, but is that possible to do that, to taper therapy?

Dr. Sikander Ailawadhi:

So, absolutely, first of all, in myeloma care, Lisa, you had mentioned initially that as somebody went to maintenance, they have had induction. So there are these terms used for categories of treatment, induction, consolidation, maintenance. But if the disease gets controlled adequately at a certain time point, the treatment can be modified to a maintenance. It depends on the regimen.

Some regimens, for example, we are able to get rid of the steroids after a certain time and then in certain regimens the drugs can be reduced in dose or frequency, et cetera. All of the drugs we use have maintenance regimens and maintenance doses. But I should put a word of caution there. I see very frequently that the moment the labs improve, this quote unquote “maintenance” is brought in.

That’s not the right way to do things. The right way is to go back to the clinical trial based on which this regimen was started. And according to that clinical trial, after however many cycles of treatment the maintenance was supposed to happen, it should happen. So if I’ll very quickly say if somebody stays, starts on a regimen and within four months their M spike comes down, and now it has plateaued. Because our drugs are so good that they work that fast. And somebody says, “Okay, four months of that is enough, let’s save it for the future. Let’s go to maintenance.” I would say, “Absolutely not.”

In fact, there is data suggested from a couple of regimens that if significant modifications were made prior to one year of the regimen, then the outcomes were inferior. And I’m not going in specific regimens and I’m not saying that that is applicable to everything, but what I’m saying is, yes, maintenance and tapering is possible. In fact, there are clinical trials looking at even stopping medication. But when and how that change is to be made is very very important. It’s critical. If your physician is not comfortable about that time point, reach out to a myeloma specialist. They should be able to guide when and how to reduce or taper or put on maintenance.

Lisa Hatfield:

Thank you. And that’s very important what you said about induction therapy. Go back to the clinical trial and look and see what the clinical trial said as far as how long that treatment should last because it is exciting as a patient when you start seeing those numbers dropping exponentially. They’re just plummeting, and you want to go off it, you don’t feel great. It’s hard to stay on a therapy for 6 to 12 months that you don’t really enjoy and nobody really does. So that’s important. And then maybe talk about maintenance therapy later. It would be nice to have limited duration maintenance, sometime in the future for induction therapy. Stick with what the clinical trial says. So, okay, this patient is asking another really important question, “I have myeloma and now my daughter does as well. She’s 37, is multiple myeloma hereditary?”

Dr. Sikander Ailawadhi:

I’m sorry to hear about this situation and I’m so sorry that your daughter who’s 37 got diagnosed. There is a small, very small number of very young patients and I’m saying using this term very young, which is just a generic thing that I’ve said because myeloma median age of diagnosis 68. I saw a patient who was diagnosed at 33 and they’re 40 now and they’ve already gone through every single thing that they can think of. And we were talking about clinical trials. So, typically myeloma is not hereditary. It is not something that is passed along through the generations. But what I would say is that there is, if this sort of a situation is happening that you have myeloma and now your daughter has it at a young age, it is important for you to consider getting genetic counseling.

So a genetic counsel for them to be able to look deeper into it. There is not a very standard specific test, so for me to say, Hey, you go and get this genetic test done and that’ll find out this mutation, whatever. But it’s important to get, go through some genetic counseling for them to be able to look a little bit deeper, some next-generation sequencing, what is called germline testing or somatic testing. They should be able to compare both the parent and the daughter’s disease as well as what’s called germline, which is their native DNA, which they were born with, to see if there is anything that jumps out of that. But that would be important to go through at a larger cancer center or if that service is available through your local physician also. That would be great.

Lisa Hatfield:

Great, thank you. Well, I think that’s it for our questions. That’s all that we have time for. But Dr. Ailawadhi, thank you so much for once again, being part of our Patient Empowerment Network START HERE Program. Because it really is these kinds of conversations that help patients, me included, feel more empowered to take questions back to our providers and our healthcare team. So thank you so much for joining us and thank you out there to everybody who’s watching this program, we appreciate you and we appreciate your time and expertise.

Dr. Sikander Ailawadhi:

Thanks and I look forward to the next time.

Lisa Hatfield:

Thank you. I’m Lisa Hatfield. Thank you for joining this Patient Empowerment Network Program and we look forward to seeing you again soon.

How is Treatment Fitness Determined in Multiple Myeloma?

How is Treatment Fitness Determined in Multiple Myeloma? from Patient Empowerment Network on Vimeo.

How is treatment suitability assessed in myeloma care? Dr. Sikander Ailawadhi, an expert from Mayo Clinic, elaborates on the factors taken into account when determining the appropriateness of treatment for myeloma patients.

Download Guide  |  Descargar Guía

See More from START HERE Myeloma

Related Programs:

What Factors Shape Myeloma Treatment Options After Relapse?

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale

Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps


Transcript:

Lisa Hatfield:

Oh, great. Okay. Again, important to see a myeloma specialist to tease out all this information. Thank you. All right. This patient is asking, “I’m 81 and living with comorbidities. The myeloma was diagnosed after bone marrow test. How is treatment fitness determined?” And also a question about that is if you’re given an ECOG status of something you don’t like it, can that be improved after you’ve had treatment?

Dr. Sikander Ailawadhi:

Absolutely.

Lisa Hatfield:

Maybe be eligible for a trial or something.

Dr. Sikander Ailawadhi:

Correct. Correct. That is so important. When this patient mentioned that they’re 81-year-old and they’re living with comorbidities, I think, so when I’m talking to a patient who’s new to me, it’s very important for me to try to tease out what was their performance status or their fitness status prior to myeloma. Because my goal is to try to get them as close to that as possible.

Now if this patient is saying that they were already quite frail before the diagnosis of myeloma and myeloma is added to the frailty, then it becomes a little tricky because we’re starting in a difficult spot. We do determine fitness by asking questions, simple questions like, what can a patient do at baseline? Can they do grocery store or grocery shopping by themselves? Can they walk around the block? Do they get short of breath? Et cetera.

And frankly, there are 81-year-olds who are playing golf every day and are fitter than me. So I’m just saying that age by itself is not the criteria. And, Lisa, like you rightly mentioned, if there are fitness issues coming from the disease itself, then that’s the time that we actually have to work with the treatment, get the treatment started, and then assess the fitness a couple of months later, a couple of cycles later. Because the treatment may have worked and may have improved the fitness quite a bit.


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Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps

Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps from Patient Empowerment Network on Vimeo.

What are next steps for myeloma CAR T-cell patients who experience relapse? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains options for relapsed myeloma patients and shares patient advice.

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See More from START HERE Myeloma

Related Programs:

What Factors Shape Myeloma Treatment Options After Relapse?

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale

How is Treatment Fitness Determined in Multiple Myeloma?


Transcript:

Lisa Hatfield:

Okay. So what would be the next steps, Dr. Ailawadhi, for a patient who’s had CAR T and reaches a relapse state or is relapsed?

Dr. Sikander Ailawadhi:

Yep. This is something, unfortunately is the truth of the matter in myeloma at least that we are, we don’t seek cures. We have had some long remissions. I have, for example, patients who are now reaching three, three-and-a-half years of remission on CAR T treatment who received it on clinical trials even before they got FDA-approved.

But, unfortunately, the disease does come back. So what happens is, we are seeing data that the novel, other novel immunotherapies like bispecific antibodies, even the ones who go after the same target as CAR T, BCMA targeting bispecifics, they do have some response rates, good response rates in post CAR T setting. So the bispecific antibodies by themselves may give us 60 to 65 percent response, but in the post CAR T setting, that response might go down to 40, 45 percent. So less responses, but still possible.

There are also bispecific antibodies. There is one available, which is not against BCMA, it is against GPRC5D. That’s a bispecific called talquetamab-tgvs (Talvey). So a novel target. There is…there are of course a lot of clinical trials. There are some clinical trials that are even looking at CAR T post-CAR T. So different kind of a CAR T. Those clinical trials are going out. So what I would suggest is that if your disease progresses after CAR T-cell treatment, you should very strongly consider getting to a specialist myeloma center and get an opinion like you mentioned, Lisa.

That is so important because the choice of treatment is extremely important at that time. And we are trying our best to sequence all the options we have, in a way, actually one of my patients mentioned, one of these days, ”Hey, does that mean that I’m basically buying time till something new and exciting comes along?” And I said, “In a way that is true. That we are trying to stretch all our treatments and get to the point that something new and promising just like CAR T comes, and hopefully we get longer benefits again.”

Lisa Hatfield:

So when you say there’s a possibility of CAR T and then a post-CAR T maybe a second CAR T. Would that be a different target then?

Dr. Sikander Ailawadhi:

So there could be a different target. I have, in fact, I saw a patient who had received one CAR T in a clinical trial and then they were subsequently able to receive a CAR T standard of care, which had been FDA-approved. So they used different CAR Ts, but one was in clinical trials and one was standard of care.


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What Factors Shape Myeloma Treatment Options After Relapse?

What Factors Shape Myeloma Treatment Options After Relapse? from Patient Empowerment Network on Vimeo.

What myeloma treatment options are there for patients who relapse? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains patient factors that must be considered in treatment options and how treatment options may be impacted.

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See More from START HERE Myeloma

Related Programs:

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale

Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps

How is Treatment Fitness Determined in Multiple Myeloma?


Transcript:

Lisa Hatfield:

For those who relapse for the first time, what are the best treatment options?

Dr. Sikander Ailawadhi:

I think that’s a very important, and I can imagine a scary situation. So somebody who relapses in general, not just even the first time, the factors that are taken into account for deciding what treatment they should get, there are broadly three categories of factors. Patient factors deciding what’s the age, what’s the other comorbidities, are they diabetic, are they heart disease, kidney dysfunction, because those things go into the decision of what may or may not be given. So patient factors.

Also importantly, how close are you to your treatment center? Can you come in for infusional or injection drugs time? And again, can you prefer or do you prefer oral drugs only? Et cetera. Those things become important. Then that…so that’s patient factors and disease factors. How fast is the progression? Is it high-risk disease, standard risk disease? Is it biochemical progression like the previous person asked?

Or is it actually a clinical progression in which there’s kidney dysfunction or anemia or bone disease? Because the choices and the urgency of treatment may change. So patient factors, disease factors, and then drug factors are the third class or third category, which is what have you had before? How long have you been on it? Are you on maintenance or not? Is your disease considered refractory to a certain agent, meaning resistant to a certain agent?

Typically, if you were on a treatment and your disease is progressing, that same drug may not be used again. And there are some times that we will reuse a drug, but generally not. We can use the same class, but we may not typically use the same drug. So I think the choice of treatment depends on all of those factors put in. And then we come up with one or two or three regimens and we discuss them with patients. And, of course, being an academic, physician, I must say there is always, you must always seek out good clinical trials if they’re available to you. That is the way our field moves forward.


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Navigating Priorities in the Expanding Myeloma Treatment Landscape

Navigating Priorities in the Expanding Myeloma Treatment Landscape from Patient Empowerment Network on Vimeo.

What should myeloma patients know about the latest treatments and monitoring? Expert Dr. Sikander Ailawadhi from Mayo Clinic shares updates about new research and treatments as well as new tools for monitoring myeloma progression and relapse.

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See More from START HERE Myeloma

Related Programs:

How Are Myeloma Survivorship and Treatment Planning Evolving?

Is There a Link Between CAR-T Therapy and T-Cell Malignancies?

What Are Guidelines for Rising Myeloma Marker Levels?

What Are Guidelines for Rising Myeloma Marker Levels?


Transcript:

Lisa Hatfield:

Dr. Ailawadhi, can you speak to the latest news and priorities in the rapidly expanding myeloma treatment landscape?

Dr. Sikander Ailawadhi:

I think, Lisa, that’s an excellent and important question. Because as you rightly mentioned, there is such a large amount of data that is coming through for myeloma all the time. I mean, it’s almost, we kind of talk about the fact that every time you turn your shoulder or look over your shoulder, there is a new drug approved. So I can imagine this can be very overwhelming. So what I’ll say is that in my opinion, there are some categories of new data that are pertinent and important for our patients.

The two or three out of them that come to my mind, one is what’s called CELMoDs, or there are a couple of agents there called iberdomide, mezigdomide. These are showing some interesting data. Important to keep in mind that they are somewhat related to the immunomodulatory drugs lenalidomide (Revlimid), pomalidomide (Pomalyst), but they’re showing benefit in patients who have had len and pom before and have progressed. So exciting stuff there.

We’re also seeing some interesting data about newer CAR Ts and bispecific antibodies. They are all coming up with some benefits in some cases. I think it’s important to keep in mind that the bispecifics are landing at the 60 to 70 percent response rate, and CAR Ts are typically landing at the 80 to 90 percent response rate, but there are more agents expected.

There are also some newer bispecifics in different classes, like one of them is called cevostamab, which is an FcRH5 inhibitor or targeting bispecific. So newer bispecific, not just more of the same category. And there has also been recent data about Bcl-2 inhibitors, which have been traditionally used for patients with translocation 11;14.

There have been some negative data, negative as in trials, which did not pan out with a drug called venetoclax (Venclexta), but there are two other drugs that had some recent data shown from different companies, which were exciting information. So in my mind, those are kind of the broad new drug categories. There is another, a couple of other quick things that I’ll mention.

One is we’re getting more and more information about real world experience with these new drugs. It’s good to see that CAR Ts are panning out very similar in the real world as they are in clinical trials. We’re also seeing that the side effect profile of a lot of these newer novel immunotherapy drugs is similar as seen in the clinical trials.

Racial ethnic disparities are something which are very close to my heart, and there is more and more information coming out in that. Unfortunately, highlighting the disparities more still rather than yet coming up with solutions. And I think the last thing that I feel which has been recent has been at the American Society of Hematology meeting in 2023, which was in December in San Diego. One of the myeloma studies actually became a plenary session presentation, which is a pretty big deal for any disease area. So one thing is that it gets highlighted. Secondly, it was a combination of a regimen called isatuximab-irfc (Sarclisa) with carfilzomib (Kyprolis), lenalidomide, and dexamethasone (Decadron) in newly diagnosed patients.

It’s a randomized trial, Phase III, which was presented. I think the important part is we saw unprecedented deep responses and patients in much, much higher numbers than before becoming MRD-negative. So very deep responses. So these are kind of some very broad, but lots of highlights that I talked about.

Lisa Hatfield:

So can you also talk about some of the newer tools for myeloma progression and relapse and what patients might want to know about that? And in particular, maybe talk a bit about MRD testing and the role of MRD testing for patients who relapse.

Dr. Sikander Ailawadhi:

Excellent question. Lisa, I think the first and foremost thing an important part for our patients to learn is what are their “tumor markers,” for the, or disease markers for myeloma. We can follow myeloma by either the M spike or monoclonal protein, by light chains, by monoclonal protein in the urine or blood. And it’s important to keep that in mind because every now and then we’ll see patients who say, Hey, my ratio changed. So I’m progressing. Well, that comes after the light chains change. So it’s important to understand the role of these things. So M spike in the urine, M spike in the serum and light chains. One of them is typically the marker for a patient.

Now the MRD status or minimal residual disease that is looking for one cell, one myeloma cell from amongst 100,000 cells in the bone marrow. So it is looking at a very deep level. The most important benefit of MRD testing right now is to understand that if a patient turns MRD negative, then they have a superior outcome. Their prognosis is better. Their progression free survival, or the time before their disease comes back is longer. 

But when a patient is MRD-negative and is being followed or maintenance or whatever, if the bone marrow turns MRD-positive, then that might be the sign that the disease might be coming back. Right now, we do not keep switching drugs to get to MRD-negative. That is not the goal of treatment. The way to think about it is we want to get to MRD-negative, but that means it’s incumbent upon us to try and pick a regimen that is more likely to get to MRD-negative. That’s the way to think about it.

Let’s pick a regimen more likely to get us into MRD-negative and hope that we get to MRD-negative. We see every now and then that the patients keep switching regimens just to get to MRD-negative. That’s not the way to go because you’re just using up options too quickly, too fast. A common question that patients ask is, well, does that mean I need to get annual bone marrow biopsies and MRD testing? Probably not.

That’s too much testing. So what I suggest is that once somebody has turned MRD-negative, it’s important to keep an eye on every single thing. Now, change in any of the routine labs, imaging, new symptoms, etcetera. That’s when we switch to the bone marrow again and see if the patient has turned MRD-positive. There are clinical trials going on right now which are stopping drugs based on repeat MRD negativity or starting drugs on MRD positivity. But those are clinical trial questions.

Lisa Hatfield:

So along those same lines, since you’re a Mayo physician, I’m curious about the mass spec testing. So if a patient say has been MRD-negative for some time, still wants to monitor at a deeper level, even though it’s not commercialized yet, do you see a role for mass spec testing on a regular basis in the future and being rolled out to community facilities also?

Dr. Sikander Ailawadhi:

Absolutely, Lisa. I did not specifically bring it up because mass spec is not, like you rightly said, is not yet commercially available. Now we’re doing mass spec quite frequently at Mayo Clinic. Basically mass spec is taking up a blood sample. Important to keep in mind, it’s not a bone marrow test, it’s a blood test, but it looks for those abnormal proteins based on the protein weight at a much, much lower level. Our SPEP or serum protein electrophoresis does not pick up very small quantities of the protein mass spec does. So in an essence, the mass spec, if somebody is negative on that, turning mass spec negative to mass spec positive may be an earlier sign of the disease coming back rather than the SPEP yet turning positive. But as you rightly said, it is not yet commercially available. I do see the benefit of it.

There is more and more data coming in favor of it, and there was data that was also at ASH. So I do see that in the future we’ll be able to most likely have it available more widely. At this point, it is just a blood test to attempt to check the disease level at a much deeper level and be able to notice if the disease is progressing sooner than our currently available tools.


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Myeloma Patient Expert Q&A: Dr. Sikander Ailawadhi

Myeloma Patient Expert Q&A: Dr. Sikander Ailawadhi from Patient Empowerment Network on Vimeo.

 In this START HERE myeloma program, Dr. Sikander Ailawadhi from Mayo Clinic spotlights priorities in the rapidly expanding myeloma treatment landscape. Watch as Dr. Ailawadhi addresses pressing questions submitted by patients and families, providing invaluable guidance and reassurance in navigating the complexities of myeloma care.

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Related Programs:

Are Myeloma Therapies Showing Deeper Responses?

How Are Myeloma Therapies and Clinical Trials Becoming More Accessible?

What Treatments Are There for Myeloma Patients Who Relapse After CAR T

What Treatments Are There for Myeloma Patients Who Relapse After CAR T


Transcript:

Lisa Hatifield:

Hello and welcome. My name is Lisa Hatfield, your host for this Patient Empowerment Network START HERE program, where we bridge the expert and patient voice to enable you and me to feel comfortable asking questions of our healthcare teams. The world is complicated, but understanding your multiple myeloma doesn’t have to be. The goal is to create actionable pathways for getting the most out of myeloma treatment and survivorship.

Joining me today is Dr. Ailawadhi, back by popular demand. Dr. Ailawadhi is a respected multiple myeloma expert from Mayo Clinic. Dr. Ailawadhi’s career focus includes the treatment of plasma cell disorders like myeloma and understanding the epidemiology and pathophysiology of this disorder. It’s always such a pleasure having you, Dr. Ailawadhi. I’m really excited you’re joining us again. So thank you for joining us.

Dr. Sikander Ailawadhi:

And thanks a lot for having me, Lisa. This is excellent. I look forward to this next iteration of the Patient Empowerment Network START HERE program.

Lisa Hatfield:

Thank you. So before we dive into today’s discussion, please take a moment to download the program resource guide using the QR code. This guide contains pertinent information to guide you both before and after the program. And this program will provide you with a comprehensive update on the latest myeloma news and its implications for you and your family. Following that, we’ll launch into some questions that we have received from you.

So let’s start here. Dr. Ailawadhi, at this juncture in myeloma history, we are witnessing unprecedented activity, a surge of new treatment options, and a wealth of insights. Today, we are privileged to have your expertise to help us decipher these developments and shed light on the advancements shaping the landscape of myeloma care. First, we’re going to get a high-level update from Dr. Ailawadhi on what the latest myeloma news means for you and your family. And then we’re going to talk about some questions that you’ve sent in. So let’s get started with the high-level update, Dr. Ailawadhi. Can you speak to the latest news and priorities in the rapidly expanding myeloma treatment landscape?

Dr. Sikander Ailawadhi:

Excellent. I think, Lisa, that’s an excellent and important question. Because as you rightly mentioned, there is such a large amount of data that is coming through for myeloma all the time. I mean, it’s almost, we kind of talk about the fact that every time you turn your shoulder or look over your shoulder, there is a new drug approved. So I can imagine this can be very overwhelming. So what I’ll say is that in my opinion, there are some categories of new data that are pertinent and important for our patients. 

The two or three out of them that come to my mind, one is what’s called CELMoDs, or there are a couple of agents there called iberdomide, mezigdomide. These are showing some interesting data. Important to keep in mind that they are somewhat related to the immunomodulatory drugs lenalidomide (Revlimid), pomalidomide (Pomalyst), but they’re showing benefit in patients who have had len and pom before and have progressed. So exciting stuff there.

We’re also seeing some interesting data about newer CAR Ts and bispecific antibodies. They are all coming up with some benefits in some cases. I think it’s important to keep in mind that the bispecifics are landing at the 60 to 70 percent response rate, and CAR Ts are typically landing at the 80 to 90 percent response rate, but there are more agents expected.

There are also some newer bispecifics in different classes, like one of them is called cevostamab, which is an FcRH5 inhibitor or targeting bispecific. So newer bispecific, not just more of the same category. And there has also been recent data about Bcl-2 inhibitors, which have been traditionally used for patients with translocation 11;14.

There have been some negative data, negative as in trials, which did not pan out with a drug called venetoclax (Venclexta), but there are two other drugs that had some recent data shown from different companies, which were exciting information. So in my mind, those are kind of the broad new drug categories. There is another, a couple of other quick things that I’ll mention.

One is we’re getting more and more information about real world experience with these new drugs. It’s good to see that CAR Ts are panning out very similar in the real world as they are in clinical trials. We’re also seeing that the side effect profile of a lot of these newer novel immunotherapy drugs is similar as seen in the clinical trials.

Racial ethnic disparities are something which are very close to my heart, and there is more and more information coming out in that. Unfortunately, highlighting the disparities more still rather than yet coming up with solutions. And I think the last thing that I feel which has been recent has been at the American Society of Hematology meeting in 2023, which was in December in San Diego.

One of the myeloma studies actually became a plenary session presentation, which is a pretty big deal for any disease area. So one thing is that it gets highlighted. Secondly, it was a combination of a regimen called isatuximab-irfc (Sarclisa) with carfilzomib (Kyprolis), lenalidomide, and dexamethasone (Decadron) in newly diagnosed patients.

It’s a randomized trial, Phase III, which was presented. I think the important part is we saw unprecedented deep responses and patients in much, much higher numbers than before becoming MRD-negative. So very deep responses. So these are kind of some very broad, but lots of highlights that I talked about.

Lisa Hatfield:  

All right. Thank you. So can you also talk about some of the newer tools for myeloma progression and relapse and what patients might want to know about that? And in particular, maybe talk a bit about MRD testing and the role of MRD testing for patients who relapse.

Dr. Sikander Ailawadhi:

Excellent question. Lisa, I think the first and foremost thing an important part for our patients to learn is what are their “tumor markers,” for the, or disease markers for myeloma. We can follow myeloma by either the M spike or monoclonal protein, by light chains, by monoclonal protein in the urine or blood. And it’s important to keep that in mind because every now and then we’ll see patients who say, Hey, my ratio changed. So I’m progressing. Well, that comes after the light chains change. So it’s important to understand the role of these things.

So M spike in the urine, M spike in the serum and light chains. One of them is typically the marker for a patient. Now the MRD status or minimal residual disease that is looking for one cell, one myeloma cell from amongst 100,000 cells in the bone marrow. So it is looking at a very deep level. The most important benefit of MRD testing right now is to understand that if a patient turns MRD negative, then they have a superior outcome. Their prognosis is better. Their progression free survival, or the time before their disease comes back is longer. 

But when a patient is MRD-negative and is being followed or maintenance or whatever, if the bone marrow turns MRD-positive, then that might be the sign that the disease might be coming back. Right now, we do not keep switching drugs to get to MRD-negative. That is not the goal of treatment. The way to think about it is we want to get to MRD-negative, but that means it’s incumbent upon us to try and pick a regimen that is more likely to get to MRD-negative. That’s the way to think about it.

Let’s pick a regimen more likely to get us into MRD-negative and hope that we get to MRD-negative. We see every now and then that the patients keep switching regimens just to get to MRD-negative. That’s not the way to go because you’re just using up options too quickly, too fast. A common question that patients ask is, well, does that mean I need to get annual bone marrow biopsies and MRD testing? Probably not.

That’s too much testing. So what I suggest is that once somebody has turned MRD-negative, it’s important to keep an eye on every single thing. Now, change in any of the routine labs, imaging, new symptoms, etcetera. That’s when we switch to the bone marrow again and see if the patient has turned MRD-positive. There are clinical trials going on right now which are stopping drugs based on repeat MRD negativity or starting drugs on MRD positivity. But those are clinical trial questions.

Lisa Hatfield:

Okay. Thank you for that. So along those same lines, since you’re a Mayo physician, I’m curious about the mass spec testing. So if a patient say has been MRD-negative for some time, still wants to monitor at a deeper level, even though it’s not commercialized yet, do you see a role for mass spec testing on a regular basis in the future and being rolled out to community facilities also?

Dr. Sikander Ailawadhi:

Absolutely, Lisa. I did not specifically bring it up because mass spec is not, like you rightly said, is not yet commercially available. Now we’re doing mass spec quite frequently at Mayo Clinic. Basically mass spec is taking up a blood sample. Important to keep in mind, it’s not a bone marrow test, it’s a blood test, but it looks for those abnormal proteins based on the protein weight at a much, much lower level. Our SPEP or serum protein electrophoresis does not pick up very small quantities of the protein mass spec does. So in an essence, the mass spec, if somebody is negative on that, turning mass spec negative to mass spec positive may be an earlier sign of the disease coming back rather than the SPEP yet turning positive. But as you rightly said, it is not yet commercially available. I do see the benefit of it.

There is more and more data coming in favor of it, and there was data that was also at ASH. So I do see that in the future we’ll be able to most likely have it available more widely. At this point, it is just a blood test to attempt to check the disease level at a much deeper level and be able to notice if the disease is progressing sooner than our currently available tools.

Lisa Hatfield:

Great. Thank you. And as a patient, I like to have one more data point that they can get from my blood, not from my bone marrow to assess the disease. So thank you for explaining that. Regarding survivorship, patients are living longer with myeloma in general because of the novel therapies that have come out in the past few years. So how is myeloma survivorship evolving, and what’s different now than it was five or 10 years ago in terms of treatment planning?

Dr. Sikander Ailawadhi:

Yeah, I think it’s very important to keep that in mind. When I see a newly diagnosed patient, I’m not just telling them, “Hey, this is your induction therapy, and your transplant is the goal.’ We’re trying our best to decide that patient’s life journey with myeloma over the next 10, 15 and hopefully more years. So we’re trying to pick and choose the regimen that is most likely going to help the patient the most today and most likely will give a longer duration of the response. So when you say survivorship, that also very importantly brings up the point that patients are living with myeloma longer. We have to manage their health overall. So looking for any side effects from treatment, managing them very well so the patient is able to stay on the treatment and maintain good quality of life.

There are actually, are clinical trials looking at stopping treatment when there is a very deep, prolonged response. Again, going towards survivorship and giving the patient’s quality of life. There is looking for other cancers. In fact, I had a patient in the clinic and we were talking about just myeloma in general and I was telling them, “Okay, please remember you may not want to do a colonoscopy, but you already have one myeloma cancer diagnosis. The risk of subsequent cancers is always there in any cancer patient.” So that was a male person. So I said, “Okay, please do not miss your colonoscopy. Please do not miss your prostate screening and whatever is age-appropriate must be done.” So managing everything because myeloma is not a sprint, it’s a marathon.

We want to make sure that we pace ourselves well so we manage all the symptoms, all the signs. Bone health becomes much, much more important because the same bone structure is now going to carry us longer and many more years. And as you rightly said, planning, which treatment comes first, which comes next, when does CAR T come? It’s not that everybody must get CAR T today. That’s not the answer. So what to use when becomes extremely more important.

Lisa Hatfield:

Thank you for that. And thank you, Dr. Ailawadhi, for that important reminder. All of you watching, get your regular screenings, like he said, prostate cancer, mammograms, colonoscopies, get it done. So thank you for that.

One of the things that comes up with that regular, not regular screening, but monitoring after certain therapies for future malignancies, there’s been some discussions about post-CAR T, particularly with T-cell malignancies and monitoring for that. Can you just give a little description of that and any concerns that you have with that or any encouragement you have regarding that and whether that weighs into your treatment options that you give to patients when they are asking about CAR T therapy?

Dr. Sikander Ailawadhi:

Absolutely. Extremely important question, Lisa. This really had a lot of discussion going on. It’s been going on for the past few months now. Okay. So first let’s explain the landscape. The FDA reviewed CAR T-cell treatment because of the fact that there were about 19 T-cell malignancies noted in several thousand patients.

Out of those 19 cases of T-cell malignancies, there was one case of multiple myeloma to the best of my knowledge. Now, risk of subsequent cancers is something, unfortunately, every cancer patient lives with, but in myeloma, we have known about that, especially from our historical knowledge of second malignancies with lenalidomide-based maintenance therapy post-transplant. So subsequent malignancies have always been a risk. There is some risk that is being talked about with CAR T, but frankly speaking, the way I look at it, the risk is significantly lesser than the potential benefit.

Because remember when these CAR T therapies, the two agents got approved in myeloma, they were approved in a situation that there was no standard therapy. And we saw somewhere about 70, 75 percent response rate with one of them and about 98 percent response rate with the other one. So in a setting where there was nothing, you can see the degree of benefit. And the risk of second malignancies is relatively small. So we must discuss this.

A patient must be aware of it, but I think the benefit is way more than the risk. So we document, we discuss, we have specific documentation that we do and specific information that we share with patients, but I think still the benefit is significantly more than the risk.

Lisa Hatfield:

Great. Thank you so much for explaining that. And for any of you out there watching this, Dr. Ailawadhi is a myeloma specialist, and I highly encourage anybody who is looking at CAR T therapy or even for a first consult for myeloma, seek out even one consult from a myeloma specialist. It is so important in trying to understand these therapies and any fears you may have regarding those therapies and the risks of that. So really appreciate that, Dr. Ailawadhi. Thank you. So I think it’s time now to start answering questions from patients that we received from all of you in the audience.

Please remember, this is not a substitute for medical care. Always consult with your medical team. And we are going to jump right in, Dr. Ailawadhi. We have a lot of questions from patients here and I’ll just start with the first one. This patient is asking, my M spike keeps rising in spite of chemo. What can I do?

Dr. Sikander Ailawadhi:

Very important question, Lisa. Every patient must understand what their disease marker is. This patient is asking about the M spike, which is the monoclonal spike, whether it’s in the blood or in the urine. And if the M spike is continuing to increase and there is a significant increase, significant is defined by at least 25 percent from the nadir or from the bottom most point with the, at least a absolute increase of 0.5 gram per deciliter. So half a gram per deciliter. So we want a 25 percent increase, but we also want at least 0.5 gram per deciliter.

So if somebody had an M spike of one at their best point, then the increase to 1.5 is significant. If somebody had the M spike of 0.2, then it’s not the 25 percent increase, it’s the 0.5 that must happen. So they hit 0.7 and that’s a significant increase. So that’s how we think about M spike, 25 percent with an absolute of at least 0.5 gram per deciliter.

If that is indeed happening, this would be considered a biochemical progression. And at that point, it should be considered to switch around the treatment because we don’t want the disease to grow to the point that there are actually symptoms showing up or organ damage happening. We want to be able to capture the disease progression sooner and act upon it.

Lisa Hatfield:

Great, thank you. Do you have any recommendations for people who, as we might have some patients watching this, who are light chain only? Any guidelines on if those numbers are rising?

Dr. Sikander Ailawadhi:

That’s an excellent question too. So if somebody has light chains as their marker, we are looking at an increase in the involved serum free light chain. So if somebody has kappa as their marker, the kappa is going up, or if they have lambda as the marker, the lambda is going up. Typically, if both of them go up, that is not disease progression. That could be coming from kidney dysfunction. Somebody is dehydrated and they get labs checked. Both kappa and lambda might be elevated. Again, a 25 percent increase in the absolute. But at the same time, we are also looking at at least 10 milligram per deciliter change.

So if somebody had a light chain of two milligram per deciliter, if it goes to 12, that might be a significant change. But I can say that light chains are a little bit more volatile and they do get affected by our fluid status. So if I ever notice a patient with a light chain increase, I’m more likely to repeat the test very soon, maybe even at a couple of days, one week interval, just to make sure that there is a trend rather than just a fluctuating light chain.

Lisa Hatfield:

Okay. Thank you for that information.

Dr. Sikander Ailawadhi:

And I should maybe, very quickly add, we do not check light chains in the urine. Light chains should be checked in the blood. Urine light chains are very nonspecific and there’s no need to test them.

Lisa Hatfield:

Okay. That’s helpful also. So patients don’t have to walk around with their big orange jugs full of fluids. So thank you. All right. This might be a complicated question to answer. But in general terms, for those who relapse for the first time, what are the best treatment options?

Dr. Sikander Ailawadhi:

I think that’s a very important, and I can imagine a scary situation. So somebody who relapses in general, not just even the first time, the factors that are taken into account for deciding what treatment they should get, there are broadly three categories of factors. Patient factors deciding what’s the age, what’s the other comorbidities, are they diabetic, are they heart disease, kidney dysfunction, because those things go into the decision of what may or may not be given. So patient factors.

Also importantly, how close are you to your treatment center? Can you come in for infusion or injection drugs time? And again, can you prefer or do you prefer oral drugs only? Et cetera. Those things become important. Then that…so that’s patient factors and disease factors. How fast is the progression? Is it high-risk disease, standard risk disease? Is it biochemical progression like the previous person asked?

Or is it actually a clinical progression in which there’s kidney dysfunction or anemia or bone disease? Because the choices and the urgency of treatment may change. So patient factors, disease factors, and then drug factors are the third class or third category, which is what have you had before? How long have you been on it? Are you on maintenance or not? Is your disease considered refractory to a certain agent, meaning resistant to a certain agent? Typically, if you were on a treatment and your disease is progressing, that same drug may not be used again.

And there are some times that we will reuse a drug, but generally not. We can use the same class, but we may not typically use the same drug. So I think the choice of treatment depends on all of those factors put in. And then we come up with one or two or three regimens and we discuss them with patients. And, of course, being an academic, physician, I must say there is always, you must always seek out good clinical trials if they’re available to you. That is the way our field moves forward.

Lisa Hatfield:

Yes, thank you for that information. So we have another patient asking, “Do myeloma patients require multiple prior therapies prior to being eligible for CAR T?” And what’s the rationale for not implementing CAR T immediately, which probably has to do with FDA approval based on clinical trials at this point?

Dr. Sikander Ailawadhi:

Absolutely. You’re absolutely right, Lisa. So any drug, let alone CAR T, any drug can only be given in the situation that it is approved by the FDA. So basically in accordance with that drug’s FDA approval label. Currently, CAR T-cell therapy is approved in the U.S. after at least four prior lines of therapy. And the patient must have had treatment with at least one proteasome inhibitor,  for which we have three drugs, bortezomib (Velcade), ixazomib (Ninlaro), and carfilzomib. They must have been treated with at least one prior immunomodulatory drug; lenalidomide, thalidomide (Thalomid), pomalidomide. And they must have been previously treated by at least one monoclonal antibody, daratumumab (Darzalex) or Isatuximab (Sarclisa).

Once the patient has had all these criteria met, they’ve become a candidate for CAR T-cell therapy. Frankly, we cannot just use a drug anywhere because we cannot use a drug where it has not shown to be of benefit. And importantly, it has not shown to be of any risk. So CAR T-cell therapy in the first line setting is being studied in clinical trials, but is not FDA-approved. Currently approved only after four prior lines, but the FDA is reviewing data for both the CAR T’s to see if they may be available sooner. As of right now, that approval is still pending.

Lisa Hatfield:

Okay, thank you. We’re hopeful that that will happen soon.

Dr. Sikander Ailawadhi:

Hopeful.

Lisa Hatfield:

Yeah. So interesting question from a patient, “Does CAR-T therapy actually change one’s DNA?”

Dr. Sikander Ailawadhi:

No. The CAR T therapy does not change one’s DNA. What happens is, there are T cells taken out of a patient. The DNA of those T cells is modified and then those T cells are given back to the patient. Those T cells do not go and integrate into your other healthy body cells or your stem cells, et cetera. Those T cells, it’s almost like giving a boost of immunity, which is targeted against your myeloma. So those T cells go in and they fill those myeloma cells. Now we hope that those T cells perpetuate and teach or create some memory T cells and that immunity lasts a little bit longer. But all of that genetic modification stays within the T cells. It does not integrate anywhere else.

Now, I know there was a previous question about T-cell lymphomas, that is related to this question in a way because the risk that is theoretical is, that that genetic modification in the T cells might make those T cells replicate uncontrollably leading to a T-cell cancer or T-cell lymphoma. But I’m saying that this is theoretical because while it is possible, it happens extremely rarely and even in the cases where the cancer happened, it has been seen that the cancer may not come from that portion of the DNA that was…that’s where the modification was done. So, low risk.

Lisa Hatfield:

Okay. Thank you very much for that.

Lisa Hatfield:

Okay. So what would be the next steps, Dr. Ailawadhi for a patient who’s had CAR T and reaches a relapse state or is relapsed?

Dr. Sikander Ailawadhi:

Yep. This is something, unfortunately is the truth of the matter in myeloma at least that we are, we don’t seek cures. We have had some long remissions. I have, for example, patients who are now reaching three, three-and-a-half years of remission on CAR T treatment who received it on clinical trials even before they got FDA-approved.

But, unfortunately, the disease does come back. So what happens is, we are seeing data that the novel, other novel immunotherapies like bispecific antibodies, even the ones who go after the same target as CAR T, BCMA targeting bispecifics, they do have some response rates, good response rates in post CAR T setting. So the bispecific antibodies by themselves may give us 60 to 65 percent response, but in the post CAR T setting, that response might go down to 40, 45 percent. So less responses, but still possible.

There are also bispecific antibody. There is one available, which is not against BCMA, it is against GPRC5D. That’s a bispecific called talquetamab-tgvs (Talvey). So a novel target. There is…there are of course a lot of clinical trials. There are some clinical trials that are even looking at CAR T post-CAR T. So different kind of a CAR T. Those clinical trials are going out. So what I would suggest is that if your disease progresses after CAR T-cell treatment, you should very strongly consider getting to a specialist myeloma center and get an opinion like you mentioned, Lisa.

That is so important because the choice of treatment is extremely important at that time. And we are trying our best to sequence all the options we have, in a way, actually one of my patients mentioned, one of these days, Hey, does that mean that I’m basically buying time till something new and exciting comes along? And I said in a way that is true. That we are trying to stretch all our treatments and get to the point that something new and promising just like CAR T comes, and hopefully we get longer benefits again.

Lisa Hatfield:

Thank you for that. So when you say there’s a possibility of CAR T and then a post-CAR T maybe a second CAR T. Would that be a different target then?

Dr. Sikander Ailawadhi:

So there could be a different target. I have, in fact, just yesterday I saw a patient who had received one CAR T in a clinical trial and then they were subsequently able to receive a CAR T standard of care, which had been FDA approved. So they used different CAR Ts, but one was in clinical trials and one was standard of care.

Lisa Hatfield:

Oh, great. Okay. Again, important to see a myeloma specialist to tease out all this information. Thank you. All right. This patient is asking, “I’m 81 and living with comorbidities. The myeloma was diagnosed after bone marrow test. How is treatment fitness determined?” And also a question about that is if you’re given an ECOG status of something you don’t like it, can that be improved after you’ve had treatment?

Dr. Sikander Ailawadhi:

Absolutely.

Lisa Hatfield:

Maybe be eligible for a trial or something.

Dr. Sikander Ailawadhi:

Correct. Correct. That is so important. When this patient mentioned that they’re 81-year-old and they’re living with comorbidities, I think, so when I’m talking to a patient who’s new to me, it’s very important for me to try to tease out what was their performance status or their fitness status prior to myeloma. Because my goal is to try to get them as close to that as possible. Now if this patient is saying that they were already quite frail before the diagnosis of myeloma and myeloma is added to the frailty, then it becomes a little tricky because we’re starting in a difficult spot. We do determine fitness by asking questions, simple questions like, what can a patient do at baseline? Can they do grocery store or grocery shopping by themselves? Can they walk around the block? Do they get short of breath? Et cetera.

And frankly, there are 81-year-olds who are playing golf every day and are fitter than me. So I’m just saying that age by itself is not the criteria. And, Lisa, like you rightly mentioned, if there are fitness issues coming from the disease itself, then that’s the time that we actually have to work with the treatment, get the treatment started, and then assess the fitness a couple of months later, a couple of cycles later. Because the treatment may have worked and may have improved the fitness quite a bit.

Lisa Hatfield:

Great thank you for that. So this person is asking, their husband is starting maintenance therapy, so I am assuming they just finished induction therapy, having leg pains mostly at night. Could this be a form of peripheral neuropathy or is maybe from bisphosphonates or from any of the medications that maybe were used during induction?

Dr. Sikander Ailawadhi:

So, excellent question. So, this is almost going back to that survivorship question that we discussed earlier, that it’s so important to manage the side effects and maintain quality of life. So, a lot of patients with myeloma will say that I have cramping or symptoms or some pins and needles at night more so. Part of it is because body’s at rest, relaxed, things, symptoms become more focused. Yes, it could be peripheral neuropathy, but at the same time certain drugs caused muscle cramping or what’s called myalgias, sometimes maintenance therapies can cause that.

It’s important for somebody to be able to determine is it coming from muscles or nerves? Is it coming because some electrolytes are abnormal. Like one of the common things is low magnesium or low potassium can cause neuropathy, for example, or cramping. I’ve had patients who will get some over-the-counter lotions or some forms et cetera, which are infused with some electrolytes and say that they feel some benefit. So topical things are good. So I think it’s important to figure out is it muscle or nerve and is it coming from drugs or disease? And that’s where your physician can help tease it out.

Lisa Hatfield:

Okay, thank you. So we have a patient who is talking about her genetic abnormalities, but has been through both auto and allo stem cell transplant in the last two years and has relapsed. And is asking, “Can CAR T-cell therapy help me?” And would she even be eligible for CAR T therapy given the allotransplant?

Dr. Sikander Ailawadhi:

That’s an important question. So first of all, sorry to hear that, that your disease is behaving that aggressively, that you’ve had both the transplants in the past two years and still having issues. So yes, CAR T can still be used after an allotransplant. There are some criteria. You should not be on any graft versus host suppressive medications, and you should not have any active graft versus host disease going on. So depending on those, yes patients can get CAR T post. And, in fact, I’ve had a couple of patients who’ve had CAR T after allotransplant.

Lisa Hatfield:

Great, thank you. I’m sure that’ll give this patient some hope. Are there any studies showing that treatment can be tapered? Tapered to by daily, once 90 percent reduction in myeloma has occurred with various therapies. So in general, you may know what medication this patient’s talking about, but is that possible to do that, to taper therapy?

Dr. Sikander Ailawadhi:

So, absolutely, first of all, in myeloma care, Lisa, you had mentioned initially that as somebody went to maintenance, they have had induction. So there are these terms used for categories of treatment, induction, consolidation, maintenance. But if the disease gets controlled adequately at a certain time point, the treatment can be modified to a maintenance. It depends on the regimen.

Some regimens, for example, we are able to get rid of the steroids after a certain time and then in certain regimens the drugs can be reduced in dose or frequency, et cetera. All of the drugs we use have maintenance regimens and maintenance doses. But I should put a word of caution there. I see very frequently that the moment the labs improve, this quote unquote “maintenance” is brought in.

That’s not the right way to do things. The right way is to go back to the clinical trial based on which this regimen was started. And according to that clinical trial, after however many cycles of treatment the maintenance was supposed to happen, it should happen. So if I’ll very quickly say if somebody stays, starts on a regimen and within four months their M spike comes down, and now it has plateaued. Because our drugs are so good that they work that fast. And somebody says, “Okay, four months of that is enough, let’s save it for the future. Let’s go to maintenance.” I would say, “Absolutely not.”

In fact, there is data suggested from a couple of regimens that if significant modifications were made prior to one year of the regimen, then the outcomes were inferior. And I’m not going in specific regimens and I’m not saying that that is applicable to everything, but what I’m saying is, yes, maintenance and tapering is possible. In fact, there are clinical trials looking at even stopping medication. But when and how that change is to be made is very very important. It’s critical. If your physician is not comfortable about that time point, reach out to a myeloma specialist. They should be able to guide when and how to reduce or taper or put on maintenance.

Lisa Hatfield:

Thank you. And that’s very important what you said about induction therapy. Go back to the clinical trial and look and see what the clinical trial said as far as how long that treatment should last because it is exciting as a patient when you start seeing those numbers dropping exponentially. They’re just plummeting, and you want to go off it, you don’t feel great. It’s hard to stay on a therapy for 6 to 12 months that you don’t really enjoy and nobody really does. So that’s important. And then maybe talk about maintenance therapy later. It would be nice to have limited duration maintenance, sometime in the future for induction therapy. Stick with what the clinical trial says. So, okay, this patient is asking another really important question, “I have myeloma and now my daughter does as well. She’s 37, is multiple myeloma hereditary?”

Dr. Sikander Ailawadhi:

I’m sorry to hear about this situation and I’m so sorry that your daughter who’s 37 got diagnosed. There is a small, very small number of very young patients and I’m saying using this term very young, which is just a generic thing that I’ve said because myeloma median age of diagnosis 68. I saw a patient who was diagnosed at 33 and they’re 40 now and they’ve already gone through every single thing that they can think of. And we were talking about clinical trials. So, typically myeloma is not hereditary. It is not something that is passed along through the generations. But what I would say is that there is, if this sort of a situation is happening that you have myeloma and now your daughter has it at a young age, it is important for you to consider getting genetic counseling.

So a genetic counsel for them to be able to look deeper into it. There is not a very standard specific test, so for me to say, Hey, you go and get this genetic test done and that’ll find out this mutation, whatever. But it’s important to get, go through some genetic counseling for them to be able to look a little bit deeper, some next-generation sequencing, what is called germline testing or somatic testing. They should be able to compare both the parent and the daughter’s disease as well as what’s called germline, which is their native DNA, which they were born with, to see if there is anything that jumps out of that. But that would be important to go through at a larger cancer center or if that service is available through your local physician also. That would be great.

Lisa Hatfield:

Great, thank you. Well, I think that’s it for our questions. That’s all that we have time for. But Dr. Ailawadhi, thank you so much for once again, being part of our Patient Empowerment Network START HERE Program. Because it really is these kinds of conversations that help patients, me included, feel more empowered to take questions back to our providers and our healthcare team. So thank you so much for joining us and thank you out there to everybody who’s watching this program, we appreciate you and we appreciate your time and expertise.

Dr. Sikander Ailawadhi:

Thanks and I look forward to the next time.

Lisa Hatfield:

Thank you. I’m Lisa Hatfield. Thank you for joining this Patient Empowerment Network Program and we look forward to seeing you again soon.


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Making Treatment Decisions | Understanding Common Myeloma Therapies

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

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

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

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Transcript:

Katherine:

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

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

Dr. Rosko:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Should You Push for a Stronger Myeloma Treatment at Relapse?

Should You Push for a Stronger Myeloma Treatment at Relapse? from Patient Empowerment Network on Vimeo.

Should myeloma patients consider choosing a more aggressive treatment at relapse? Expert Dr. Jeffrey Matous explains the revised approach to choosing treatment at this stage and shares examples of second-line therapies that may be options for relapsed patients.

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

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Transcript:

Katherine:

Kendall writes, “I’m in the maintenance stage following initial diagnosis and treatment. At first relapse, is it appropriate to push for stronger treatment in hopes of a cure?” 

Dr. Jeffrey Matous:

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

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

What Is Known About the Risk of Myeloma Relapse?

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

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

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

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Transcript:

Katherine:  

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

Dr. Derman:  

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

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

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

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

What Are the Treatment Options for Relapsed/Refractory Myeloma?

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

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

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

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Transcript:

Katherine:

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

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

Dr. Derman:

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

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

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

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

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

What Treatments Are There for Myeloma Patients Who Relapse After CAR T?

What Treatments Are There for Myeloma Patients Who Relapse After CAR T? from Patient Empowerment Network on Vimeo.

Do multiple myeloma patients who relapse after CAR T have other treatment options? Dr. Sikander Ailawadhi from the Mayo Clinic explains patients who typically receive CAR T-cell therapy and options for those who relapse after CAR-T therapy.

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Transcript:

Lisa Hatfield:

So this next question has to do with the sequencing of treatments, which, again, speaks to the fact that it’s super important to see a myeloma specialist, but the question is what treatments are available for myeloma patients who relapse after CAR T?

Dr. Sikander Ailawadhi:

Very, very important question, and unfortunately a tough situation that we are dealing with because CAR T initially has been used for later lines of therapy as it is currently FDA-approved. With time, hopefully it will start making it may sooner in the treatment also, but when a person…when a patient has had treatment with CAR T, generally, they have already had treatment with most of the standard available drugs prior to CAR T, because the way CAR T is currently approved is the patient has to have at least four prior lines of therapy, and generally, at least in the U.S. system, with the first three to four regimens or lines of therapy, we’ve already seen and exhausted most of the available drugs.

So you can imagine most CAR T, there is less drug availability that the patient has not had before or may not be resistant to, but if the CAR-T response lasted long enough, sometimes we are recycling some of the drugs after previously used, and the patient may respond to them again.

Another thing to think about in that place is from my standpoint, clinical trials are extremely important and patients must seek clinical trial options, as you mentioned, again, important to see a specialized myeloma center, but one of the drugs that was approved in 2022 bispecific antibody, teclistamab (Tecvayli), and there are some other related by specific antibodies which have actually shown some benefit despite the fact that they also target BCMA, which CAR T targets, but patients who had prior BCMA therapy still had a very good response rate to, for example, teclistamab or some other…bispecific antibodies in clinical trials, so I don’t say that everybody who’s been treated with a BCMA CAR T should go immediately to a BCMA and bispecific may not be the best option in all cases.

But sometimes recycling older drugs in certain different combinations, clinical trials or options promising options like bispecific antibodies. We do have more options today than even what we had a year ago for patients who are progressing after CAR T-cell therapy. 

What Are Some Clinical Myeloma Relapse Predictors?

What Are Some Clinical Myeloma Relapse Predictors? from Patient Empowerment Network on Vimeo.

Some multiple myeloma patients may relapse, but are there clinical predictors for relapse? Dr. Sikander Ailawadhi from the Mayo Clinic discusses mutations, clinical responses, and test results that may signal a higher likelihood of relapse.

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Transcript:

Lisa Hatfield:

Great, what are some of the clinical predictors for relapse in myeloma and when should patients speak up?

Dr. Sikander Ailawadhi:

Okay, so when we say clinical predictors of relapse, well, let me look at this from the standpoint of a patient’s been diagnosed, they’ve been treated, which patients are more likely to relapse is one way of looking at, and if we are looking for our following up a patient, what are we monitoring to look for relapse? So I’ll address mutates very quickly. So when we say what are the predictors of earlier relapse, the most important things that we know of are on any of the high-risk communications we’ve been talking about, the fact that it’s standard of care to look for any genetic mutations in the center diseased plasma.

So the myeloma cells, presence of any high-risk mutations, for example, there’s one called deletion 17p to certain chromosome mutations like 14;16 translocation, etcetera. Patients should be aware of what mutations their plasma cells have, having high-risk mutations, risk of early relapse or short duration of response.

Similarly, if a patient does not get a deep response to their prior treatment, they are more likely to come out of that response state sooner. One of the tests that has recently been used over the past few years, there’s something called the MRD test, minimal residual disease test, looking for one myeloma cell out of 100,000 or even one million bone bone marrow cells.

If somebody’s MRD-negative, they are more likely to have a longer duration of response. If they’re MRD-positive, meaning detectable disease on MRD test, comparatively shorter duration of response, etcetera. So these are predictors of earlier relapse, there are some other predictors like kidney dysfunction, and typically that happens if somebody has persistent kidney dysfunction because they don’t typically get access to all the drugs, typically relapse occurs sooner.

Now, when somebody is getting monitored for their disease, as I mentioned, we do labs every so frequently every month, every two months, every three months. That is what involves all the myeloma markers, serum lectrophoresis is to look for M spike, free light chains, look for light chain changes. You see what I mean? We know globules look for increases in immunoglobulins, and that’s what helps pick up the recurrence of the disease. 

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. 

Understanding Relapse in Myeloma

Understanding Relapse in Myeloma  from Patient Empowerment Network on Vimeo.

What are indicators that a myeloma patient has relapsed? Dr. Mark Schroeder explains how relapsed and refractory myeloma are monitored and treated. 

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:

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:

I think you’ve already answered this, but I’m going to ask you in case you give different or more information. 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.