Tag Archive for: myeloma research

PODCAST | Evolving Myeloma Treatment Options: How You Can Access Cutting-Edge Care

 

 

With the quickly evolving landscape of myeloma treatment and care, it’s important to work with your healthcare team to determine a care plan. In this program, Dr. Omar Nadeem discusses the latest updates in research and clinical trials, the role of new and emerging therapies– including bispecific antibodies and CAR T-cell therapy–and shares advice for accessing quality myeloma care.

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

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Transcript:

Katherine:

Hello, and welcome. I’m your host, Katherine Banwell. As patients collaborate on treatment decisions with their healthcare team, it’s important that they understand all of their options and how these options may be impacted by research developments. That’s why the Patient Empowerment Network created the Evolve series, to arm you with the latest information and help you feel empowered and confident during conversations about your myeloma care.  

In today’s program, we’re going to hear from an expert in the field about the evolving treatment landscape and discuss how you can play an active role in your care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what may be best for you. Well, let’s meet our guest today. Joining us is Dr. Omar Nadeem. Dr. Nadeem, welcome. Would you please introduce yourself.  

Dr. Nadeem:

Thank you. Hi, everyone. My name is Omar Nadeem from the Dana-Farber Cancer Institute. It’s my pleasure to be here.  

Katherine:

Thank you so much for joining us today. Before we get into our discussion, would you share with the audience how the field of myeloma care has changed over the course of your career?   

Dr. Nadeem:

Yeah, and things are changing so rapidly. My career started after my training in 2015 and at that time, daratumumab (Darzalex) just had its approval in relapsed/refractory multiple myeloma. That, along with several other monoclonal antibodies a few immunomodulatory drugs and proteasome inhibitors.  

At that time, it felt like myeloma was at the forefront of significant advances and change in practice, which it was. Little did we know that we were right around the corner with the next renaissance of myeloma therapy, which is these immunotherapies that have been approved over the last three to four years now. So, safe to say things are changing so, so fast and it’s leading to excellent outcomes for patients.  

Katherine:

Yeah, it’s great news. So positive. I’d like to start with the importance of a patient’s healthcare team. What are the benefits to seeking care with a myeloma specialist, even if it’s just for a second opinion or a consult? 

Dr. Nadeem:

Yeah, so, myeloma is a little less than 2 percent of all cancers, and it’s the second most common blood cancer, so certainly not rare. With that being said, if you go to a general community practice, they don’t typically see too, too many patients with this disease. So, alongside that, we have so many different treatment options and combinations and these, as I mentioned, immune therapies.  

And other therapies that are only actually carried out at academic centers for now, such as stem cell transplants, and CAR T-cell therapy. I think it’s important to kind of meet with an academic provider just to get a sense of what the patient may be facing, both in that immediate time, but also in the future, because a lot of myeloma therapy is lifelong. And in that case, you do have to come up with a plan for your whole treatment in a way early. So, it’s important to kind of one: hear it from another person, and then two: really sort of figure out what the outlook would look like for the individual patient.  

With that being said, many of our myeloma regimens that are approved can very easily be given at the local provider, and that’s usually our preference, for patients to be treated closer to home. So, ultimately, this is another way for patients to get input about their treatment program, but also talk about the future.   

Katherine:

That makes sense. Specialists at academic medical centers are typically more involved in research and clinical trials. 

And patient participation is essential to advancing medicine. So, how do clinical trials impact myeloma care? 

Dr. Nadeem:

Well, everything that we have available today for myeloma therapy was once in a clinical trial. So, all these promising therapies usually start in early phase studies and move on to Phase II and Phase III studies, and then those are the ones that the FDA uses to approve a particular combination.  

So, it all depends on kind of where someone is in their disease course. It also kind of depends on what their preferences may be in terms of taking on something that is beyond standard of care. So, as part of any clinical trial in whatever phase it may be, whether its newly diagnosed multiple myeloma, even smoldering myeloma, which is one step before that, relapsed/refractory myeloma.

At each step of the way, there are clinical trials that are there trying to improve upon what’s already out here, right? So, we are, despite all these amazing advances, unfortunately, the disease is still not curable for a vast majority of patients.  

In that case, how do we move to that cure, or how do we kind of advance the disease even beyond this? And a clinical trial is a way to do that.  

Katherine:

What type of patient is most appropriate for a clinical trial? 

Dr. Nadeem:

So, there are criteria that each clinical trial uses in terms of eligibility. Some of that has to do with the disease characteristic itself, kind of where somebody is in their disease course, but many times it’s also patients’ fitness, organ status in terms of kidney function, their blood count to some extent, heart function, etcetera. There are some sort of minimal prerequisite guidelines that we have to enroll patients in trials. So, it really, again, depends on where somebody is in their disease course and what they may be willing to take on beyond what may be offered to them as part of standard of care.  

Katherine:

What questions should patients be asking if they’re entrusted in participating in a clinical trial? 

Dr. Nadeem:

I think the important thing is to sort of first recognize what’s available to them as part of standard of care and then what the clinical trial is trying to answer.  

So, for example, if it’s newly diagnosed multiple myeloma, we now have quadruplet regimens that we give to patients at the time of their diagnosis, and then the next natural question for eligible patients that now comes up is whether they should do a stem cell transplant or not.  

And alongside that goes with all these advances in immune therapies, such as CAR T-cell therapies and bispecific antibodies. And there are now trials looking at those therapies and comparing them, for example, to stem cell transplant to try to answer the question “Can we get even beyond something like a stem cell transplant?” 

So, that’s one example of a trial where a patient may be interested in saying “Okay, well, a transplant may be my standard path, but what if I try to enroll in this study and get randomized, for example, to the CAR-T arm? Then, perhaps, I’m getting access to some of these therapies early and maybe that’s going to improve my outcomes.” 

Katherine:

Well, I’d like to talk about some new and emerging therapies in myeloma, starting with CAR T-cell therapy. Can you talk about who this treatment option might be appropriate for? 

Dr. Nadeem:

So, yeah, just to kind of give folks background, CAR T-cell therapy is a form of immunotherapy, where we take out an individual’s T-cells and then re-program them, essentially, to recognize myeloma cells. Right now there’s two approved CAR-T products for multiple myeloma, both in the relapse refractory setting. It’s really for patients that have had four or more lines of therapy.  

So, that’s a lot of different combinations that we currently have available. Those therapies stop working before patients are actually eligible for CAR-T cells at the moment. Both of these CAR T-cell products have been gamechangers in terms of improving prognosis for patients.  

The good thing about CAR-T cells is that it is a one-and-done treatment. So, patients, when they go through that initial phase of therapy, they are then off therapy, although we are now starting to study certain therapies that we may administer after CAR-T cells to get them to last even longer than they currently do, but that’s still in, for example, that’s one of the clinical trials or many of the clinical trials that are currently ongoing now, to try to answer that question.   

So, a lot of patients can be eligible for CAR-T cells. They have to have the prerequisite amount of therapies. Again, there are some sort of baseline fitness characteristics that we look at for patient’s ability to tolerate it. But as a whole, I consider CAR T-cell therapy more broadly applicable to myeloma patients than compared to, let’s say, a stem cell transplant.   

Katherine:

How has this therapy revolutionized myeloma care? 

Dr. Nadeem:

Yeah, before the first approval, now a few years ago, in this space we didn’t really have anything like this to offer patients. So, many of the combinations and other compounds that were in clinical trials would have a response rate somewhere around, let’s say, 30 percent. So, 30 percent of patients may respond to that therapy in that space, and that may only last a few months, and that was considered successful not that long ago. Now, with CAR T-cell therapy and bispecific antibodies, these therapies are highly efficacious.  

You see response rates of 70 to 100 percent in some of these immunotherapies, and what that’s translating into is patient’s disease staying away for a year or two years, even three years in some of these clinical trials. And again, this is completely unprecedented compared to what we had before.   

Katherine:

I understand that there are a number of clinical trials for different types of CAR T, or even using it earlier in the disease. Can you share updates in CAR T-cell therapy research? 

Dr. Nadeem:

Yeah, so, exactly as you pointed out, there have been trials already, actually, that have been completed, Phase III studies looking at CAR T-cell therapies in earlier relapses.  So, patients that have had either one of two lines of therapy. 

Both our CAR-T therapies have been compared to standard of care in that space and have shown superiority, and this is something that we all have been kind of waiting for to see if you deploy it earlier, perhaps you’re going to see even greater benefit, and that seems to be the case in some of these trials, and now we’re awaiting, hopefully, approval of some of these CAR T-cell therapies to be administered earlier because in fifth line, it’s very different than treating patients in second or third line, which I think will really vastly improve our ability to deliver this therapy to many patients, as it can be quite challenging for patients that are in fifth line, to allow them to go through the process of CAR-T cells and then having them be administered.  

I was looking at it head-to-head with stem cell transplant, as I mentioned before, and this is in the context of quadruplet and induction therapy followed by either CAR-T cells or stem cell transplant, and then followed by maintenance therapy. So, really trying to see if I can overcome what we typically have achieved with stem cell transplantation. 

We also are doing some studies even before that. So, patients, again, in high-risk smoldering myeloma, which we know have an increased risk of developing newly diagnosed disease in the next few years, perhaps that could be the time where we can give some of these immunotherapies, and that’s some work that we have going on at our center. 

Katherine:

Well, another therapy that has emerged in myeloma is bispecific antibodies. What patient type is this therapy right for? 

Dr. Nadeem:

So, bispecific antibodies are great because they’re off the shelf. What that means is that CAR-T cells, we first have to collect the T cells and we then have to send them off to be manufactured, and that manufacturing process can take up to a month, sometimes even longer, for some of the current available CAR-T products. And then, after the cells are returned to the facility, we then give usually three days of chemotherapy to try to suppress some of the immune systems of the patients. So, that way, when the cells are administered, they can expand robustly and do essentially what they need to do. 

So, that whole logistical process can take a couple of months by the time you identify somebody for CAR-T cells and then, from that moment until they can actually be treated. With bispecific antibodies, if we think somebody’s ready to go, you can basically get it as soon as we can have somebody ready to go either in our clinic or on the in-patient facility. So, they’re much easier. They also utilize T cells to attack myeloma cells. We now have three approved bispecific antibodies. Two of them are targeting BCMA, the same exact target that we have in CAR-T cells, and one of them is now targeting a new target called GPRC5D, which is also highly expressed on myeloma cells.  

So, having all these bispecific antibodies available is excellent because patients can have access to them a lot faster and now we’re trying to answer the question of sequencing. Can you give bispecific antibodies after CAR-T cells for example? Can you give one bispecific antibody after another, especially if there’s a different target that we now have available? 

As a whole, though, bispecific antibodies tend to have lower response rates than CAR-T cells, particularly Cilta-cel (Carvykti), which is cilta-cel that has a very high response rate of close to 100 percent.  

Most bispecific antibodies have response rates somewhere around 70 or so percent, so about two-thirds of patients respond to these therapies, again, in that fifth line or four or more lines of therapy. So, in that space, that’s the response rate. And across the board, generally speaking, patients benefit from these bispecific antibodies approximately a year on average. Some of the studies have shown longer benefit, and it also depends somewhat on response to therapy.  

Patients that have a really deep response can go even way longer than that. So, it is quite mixed in terms of how somebody may do on these bispecific antibodies, but those are the numbers.  

Katherine:

Well, it sounds like bispecific antibodies have really transformed myeloma treatment options.  

Dr. Nadeem:

Absolutely, and what goes hand in hand in this.  

I mentioned the logistics of CAR T, but then there’s also the supply and availability of CAR-T cells. Since the approval, the demand for CAR-T cells has been very high because of all these excellent results, but the supply really hasn’t been there. So, even at a center as busy as ours, we can only treat a handful of patients with CAR T-cell therapies compared to bispecific antibodies, where that is essentially an injection similar to many other approved myeloma agents that you can just readily treat patients with. So, CAR-T cells, while I think, again, have higher efficacy, with that comes slightly higher toxicity as well. It’s a very different kind of treatment program.  

And then, patients get a treatment-free interval, which you don’t see yet with bispecific antibodies. On the other hand, bispecific antibodies are readily available, slightly lower response rates, slightly lower toxicity when it comes to at least the traditional T-cell directing toxicities. And then you have, again, the readily available nature of it, which I think is hugely beneficial for patients.  

Katherine:

You talked about some specifics regarding bispecific antibodies, but are there updates in bispecific antibody research that you’d like to share? 

Dr. Nadeem:

Yeah, so, again, kind of following the theme of what we just said about CAR-T cells, can you bring these antibody therapies earlier? And there’s ongoing trials now looking at it in newly diagnosed multiple myeloma and early relapses, and then we presented our data at ASH this previous year looking at it in high-risk smoldering myeloma. We treated patients with teclistimab (Tecvayli), which is a BCMA bispecific antibody that is approved for relapse refractory patients. And what we demonstrated in that study is that people that got Teclistimab had a 100 percent response rate with an MRD-negative rate. So, kind of as deep of a response as we can measure, also at 100 percent.  

So, this is something that we had not seen before. When their immune systems are a lot healthier, they may benefit more. So, hopefully we’ll see confirmation of these results in other trials.  

Particularly in the newly diagnosed space because we do think that these antibody therapies have such huge potential to treat patients, and then hopefully we’ll have durable responses. So, I do think that some of this paradigm may shift over the next few years, and then there’s also combinations that are currently being studied: combinations with traditional myeloma therapies, such as monoclonal antibodies, other immunomodulatory agents, or proteasome inhibitors. All these combination trials are now ongoing to see can you improve upon some of those numbers that I highlighted before with single-agent bispecific antibody therapy. 

Katherine:

Oh, I was just going to ask you the next question, which is are there other emerging myeloma therapies that are showing promise? 

Dr. Nadeem:

Yes. So, I think over the last few years, most of the buzz has been with these immunotherapies. And, again, more work to be done there to see whether combinations, different schedules, different targets, different types, will show more and more benefit in each of these myeloma disease settings.  

But we also have simultaneous development of other agents that are not in this sort of immunotherapy T-cell redirecting therapy realm. We have newer versions of our classic immunomodulatory drugs, such as lenalidomide (Revlimid) or pomalidomide (Pomalyst).  

We now have their next generation agents, called CELMoD drugs and there’s two of them in development. One of them is called iberdomide; one is called mezigdomide.  

These are, again, kind of building up on the success of some of these previous therapies that are kind of cornerstone therapies for myeloma patients and because these are essentially better agents, they’re more targeted, and they also have greater response rates as single agents and as combinations.  

We’re hoping that these would be approved in the not-so-distant future and then perhaps will replace some of these immunomodulatory drugs that we have currently utilized in newly diagnosed and relapsed myeloma. Essentially what this means is things are just getting better and better and better as we get newer versions of some of these therapies. So, those are, I would say, kind of next in line in terms of hopeful approvals.  

And then we’ll add to some of the options that we have for myeloma patients.  

Katherine:

How can patients and care partners stay informed about the latest myeloma research? 

Dr. Nadeem:

Yeah, it’s a lot of moving parts all the time. From one six-month interval to the next, you tend to have nowadays perhaps some drug approvals, which is amazing, but if not updates of all these sort of combination trials, etcetera, of where these things are going. I think kind of talking to your physician, obviously, about some of these updates is really critical. As I mentioned before, having a roadmap in your mind about what the myeloma therapy for you might look like going forward, wherever you are in your disease state, is always important because it gives you time to sort of think about it, learn about it, prepare for it.  

Some of these therapies really require an effort from the patient and their caregivers because, for example, for CAR-T cells. If you’re not near a center, you may have to relocate for a month.  

And it’s very difficult, and we fully understand that and try to help as much as we can, but that’s the kind of commitment that it takes. So, talking to your physician, obviously content like this, reviewing this as much as you can. Online patient support groups are great because you learn from the other patients’ experiences. So, the good news now is we have so many channels of communication, but you have to in a way, in the end, discuss with your physician and verify things you may find on your own.   

Katherine:

Exactly, yeah. You want to make sure you’re getting facts rather than fiction.  

Dr. Nadeem:

Yeah. That’s right.  

Katherine:

Well, Dr. Nadeem, we’ve been hearing the term personalized medicine more frequently in recent years. How would you define personalized medicine for myeloma, and how can patients access this type of care? 

Dr. Nadeem:

Yeah, personalized medicine or precision medicine is a term that we’ve really sort of used for many oncologic conditions over the last decade or so. I would say, for multiple myeloma, in terms of identifying a target within the myeloma cell that’s unique to the patient.  

And then deploying a certain therapy to that patient because of that target is still lacking. We do have one example where patients have, for example, an 11;14 translocation, which we see in about 15 percent of myeloma patients.  

There’s an agent called venetoclax (Venclexta) that is very active against that particular cohort of patients, although that is still not approved to be used, but that’s one example where that agent specifically benefits that type of myeloma. Other than that, most of the therapies that we have benefit essentially everybody with myeloma, which is great, but it’s not so personalized.  

Where I would say there’s the most personalization happening now, at least in my practice, is looking at which types of therapies an individual patient may receive. What I mean by that is if somebody’s in an excellent response, with quadruplet-based induction therapy, I have a very real discussion with them about the pros and cons of stem cell transplant. We make those decisions in real time depending on how the patient doing, depending on how their response is.  

And then kind of deciding a whole kind of what are the kind of risks and benefits and what makes sense for that individual patient. Similarly, when you go on to maintenance therapy, maintenance therapy means that after you’ve gone through the initial phase of your myeloma therapy and the disease is under control, what type of therapy can we keep you on to keep it under control for as long as possible? Historically, that has been lenalidomide or Revlimid. Now we’re adding drugs such as daratumamab and other agents to Revlimid to see if that can further prolong the response to that initial therapy.  

So, all those decisions are so individualized that you have to discuss with your provider what makes sense for you and what are the pros and cons of doing one approach versus the other.  

Katherine:

Well, if we’re talking about in-depth testing, how do the results of that testing affect treatment options? 

Dr. Nadeem:

So, right now we use conventional blood tests to get a sense of response in the vast majority of patients. That includes the serum protein electrophoresis and the serum free light chain assay.  

Most patients have detectable levels of these proteins, abnormal proteins in the blood at diagnosis and then you can follow them using a blood test. There’s a subset of patients that have disease only that shows up on scans. So, we then kind of incorporate some of those scans and then, also, utilize the bone marrow results both in the beginning and in subsequent analyses to kind of give a big-picture composite response assessment for that particular patient. Nowadays, there are also other tools that we’re using, such as MRD, or minimal residual disease.  

That is a test that is done on a bone marrow biopsy to determine, if you don’t have detectable protein in the blood, do you have myeloma cells present at the deepest level possible? And if you do versus if you don’t, trials have shown that there is a difference in terms of prognosis. Now, while that hasn’t fully been utilized yet to make treatment decisions in patients that are not on clinical trials, we do get prognostic information out of it, and nowadays, more and more of those trials are using these MRD tests to determine what to do with treatment.   

And I think that’s how it’s going to be in the future. So, having those extra tests available but, again, important to discuss with your provider what is the utility of this test. How are we going to use this information for your individual case to make some decisions? 

Katherine:

What questions should patients be asking their provider about a proposed treatment plan?  

Dr. Nadeem:

Yeah. I think because myeloma therapy’s so nuanced and much of this is still in clinical trials or under investigation about what to do with some of these results, I would say, as a whole, it’s important to know which tests the physician looks at to determine how you’re doing, and kind of what their assessment of that result is. So, for example, if somebody’s had a 50 percent reduction in the amount of abnormal protein in the blood, is that sufficient, or should we be aiming for a number that’s much higher than that? 

Some of that depends on kind of where they are in their treatment course, but that’s a very sort of reasonable question to ask your physician is that where do you see my response now, let’s say six months into therapy, and is this adequate, and what is now, after we have all this information, what is my roadmap going forward to try to keep this disease in check? 

Katherine:

Yeah. Well, that’s great advice, Dr. Nadeem. Thank you. PEN has also created a downloadable office visit planner to help you organize your thoughts and communicate effectively with your healthcare team. You can find these at Powerfulpatients.org/myeloma.  

I’d like to turn to self-advocacy, Dr. Nadeem. Why is it so important that patients engage in their care treatment decisions? 

Dr. Nadeem:

Yeah. As I mentioned, myeloma therapy is so individualized now and we can sit here, look at the trial data, get very into the weeds and technical about this therapy with this approach as X or Y higher response rate.   

Or MRD-negative rate, but in reality, we’re dealing with people and we’re dealing with people that have lives. They have all their priorities, and until you share that with us, it’s very difficult for us to know exactly what’s important to you. So, what I may consider to be kind of the “best therapy” for you may not make sense for you because of all the priorities that you may have, and I think it’s so important to advocate for yourself and not be afraid to bring that up to your physician because I think many patients kind of hold that stuff in for a long time because they don’t want it to impact their care. But I would argue the other way around.  

Tell us. Tell us exactly what you prioritize. Tell us if you can’t be out of commission for work for X amount of time because of a stem cell transplant. We now have options. We now have options for patients because of all these amazing new therapies for myeloma and we can come up with a very individualized treatment plan for you based on your priorities.  

Katherine:

If a patient is feeling like they’re not getting the best care or they’re uncomfortable with the care they’re receiving, what steps should they take to change that?  

Dr. Nadeem:

Yeah, I think that’s very difficult because this is a complex system. Medical systems are getting even more and more complex. They’re busy. Everybody’s busy: busy offices, labs, radiology. We’re all feeling that. It doesn’t matter where you are. So, I think it’s important to raise those concerns, number one, to your practice that you’re being seen at because they would like to see that feedback, right? So, kind of see what is something that they can perhaps improve upon. I think it’s always important, like we just said, to advocate for yourself and raise some of these issues and not be afraid of that.  

We’re all in this together, right, so I think ultimately, we’re all trying to take the best care of you and we would need to know which part of that may or may not be working so well.  

Katherine:

Let’s get to a few audience questions that we received prior to the program. This one is from Rita. “Is there an age limit on CAR T-cell therapy?” 

Dr. Nadeem:

So, no, there isn’t. A lot of age-related cutoffs that we’ve historically used for transplants or even the CAR T originally don’t really apply because we all know there’s patients that are in their late 70s that may be more fit and robust than somebody in their 50s. We see this all the time. So, frailty is something that we assess quite a bit in patients in determining whether they can handle some of the toxicities that may come from these therapies. So, there’s no age cutoff.  

Again, we look at certain other medical problems you may have, how fit you are, your organ function and things like that, but ultimately the goal is can you tolerate the chemotherapy you get before CAR-T cells and then can you tolerate some of the acute toxicities of CAR-T cells, such as the cytokine release syndrome, some risk of neurological toxicity, things like that. All of those are usually short-term, and if you feel confident that we can get you through that, then you’re eligible.  

Katherine:

Yeah. Laura sent in this question: “I’m considering bispecific antibody therapy. I know some of the side effects are similar to CAR T-cell therapy. Can you share the pros and cons of bispecifics and how it compares to CAR T?” 

Dr. Nadeem:

Yeah. I think we mentioned earlier that as a whole, they’re very similar. They’re both T-cell re-directing therapies, in many circumstances, with the same exact target of the myeloma cell, but because this isn’t a cell infusion – this is a cell injection – that you receive that redirects your T cells to the myeloma cells, you tend to see a little bit of a lower toxicity signal when it comes to the cytokine release syndrome incidents and severity. You see lower neurological toxicity, usually, than you do with CAR  T-cell products as a whole.  

With that comes slightly lower efficacy than you see with at least some of our CAR-T products, but if you respond to therapy, then the durability of response can be as good as you can achieve with CAR-T cells. One thing to note about the bispecifics, though, is that it is continuous therapy, so you are getting it on some regular schedule. Right now the approval is for it to be given weekly and then go to every two weeks after six months of therapy if you’re basically in a good response.  

A lot of that is to try to mitigate the risk of infection. So, that is one of the biggest things that we have seen with bispecifics more so than CAR-T cells. Because it is continuous administration of these therapies, that really suppresses your immune system significantly, and infection rates are quite high. So, we typically give other ways to try to mitigate that using immunoglobulin infusions to try to boost up your immune system. Typically, we do that once a month for patients, making sure you’re on the right prophylactic medications and then really adjusting the therapy and the schedule to you depending on your tolerability.  

So, as we said before, it’s an excellent option. I think bispecific antibodies are going to be the mainstay of myeloma therapy going forward because CAR-T cells, again, we can’t really treat everybody with CAR-T cells just simply because of the dynamics of how the process is. So, having the bispecific antibodies available for patients is excellent.  

Katherine:

Thank you for this information, Dr. Nadeem. And please continue to send in your questions to questions@powerfulpatients.org and we’ll work to get them answered on future programs.  

We’ve definitely learned today that the field of myeloma care is advancing quickly. As we close out the program, what would you like to leave the audience with? Why are you hopeful? 

Dr. Nadeem:

Yeah. I think you all can see the tremendous progress that’s been made and, again, I still think it’s sort of the tip of the iceberg. These immunotherapies that are really showing this kind of activity, we’re just learning about them, and we’re going to improve them, not just the way we administer them. We’re going to make them even better and better and better and our hope is that a cure is not so far in the future. And perhaps even now we can cure a subset of patients if we deploy some of these therapies in the right person at the right time. So, I think that is really what I am hopeful for, that we have all these options available.  

Now it’s up to us to figure out which one fits in where and then, as we do that, hopefully we’ll see even better and better outcomes. And my hope is, over time, that this is a disease that we can cure at least in a subset of patients, which means that they get fixed duration therapy with whatever that we have.  

And then they’re done, and then hopefully never have to have therapy for this disease because it’ll be gone, and then, in patients that develop a disease relapse, we then treat them with some of these other agents. So, this is starting to hopefully mirror what we see in other blood cancers, such as lymphoma, for example, where you give the initial therapy and cure a subset of patients. Hopefully we can get there with myeloma in the not-so-distant future.  

Katherine:

It’s a very promising outlook to leave our audience with. Dr. Nadeem, thank you so much for joining us today. 

Dr. Nadeem:

Thank you so much for having me.   

Katherine:

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

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.

Download Guide  |  Descargar Guía

See More from START HERE Myeloma

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.

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.

Download Guide  |  Descargar Guía

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?

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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.

Download Guide  |  Descargar Guía

See More from START HERE Myeloma

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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Understanding Distinct Barriers to Myeloma Clinical Trial Participation

Understanding Distinct Barriers to Myeloma Clinical Trial Participation from Patient Empowerment Network on Vimeo.

What are some ways for myeloma advancements to be driven forward? Expert Dr. Beth Faiman from Taussig Cancer Institute discusses additional solutions to help research efforts for diverse participation in clinical trials.

Download Resource Guide|Descargar guía de recursos

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Transcript:

Dr. Nicole Rochester:

Are there any additional solutions that you think are necessary as we continue to see advancements in myeloma?

Dr. Beth Faiman:

Continuing education for these highly trained providers. And so those kind of…the education though, I’ll tell you, I think should focus a lot on the disparities in clinical research. One of the things I’m passionate about is highlighting the implicit and explicit biases that are in clinical research. Many of us will say, “Oh, that person won’t be a good clinical trial candidate because they live too far away or they don’t have a caregiver.” And so I’m really…I tell all of my nurses, nurse practitioners, even physicians, just ask a patient. Don’t think that because they live an hour away, they’re not going to want to participate in a well-designed clinical trial without even asking them. That doesn’t even allow them the opportunity to provide feedback.

And then not to mention all of the resources that are available to patients that provide, that participate in clinical trials. Many of the research studies will provide transportation or an overnight stay or some nominal, again, not trying to coerce the patients, but some nominal reimbursement for expenses to allow them to have access to that drug. So I can talk on and on, because I’m so passionate about this topic. But being aware that biases exist, through continuing education will hopefully enhance the diversity of clinical trials so that patients will be able to have access to care, and then that the clinical trial results are representative of the actual population of who we’re treating.

Dr. Nicole Rochester:

Thank you. I can definitely feel they’re both of your passion, and that’s why it’s so important that we have you here with us today for this conversation. So let’s shift focus a little bit and begin to talk about communication between healthcare providers to effectively communicate about pretrial eligibility determination and the consent process. So I’m going to go right back to you, Dr. Faiman. What do you think are the unique barriers that providers face when they’re speaking about myeloma trials to patients and their families?

Dr. Beth Faiman:

Right. So I think multiple myeloma is unique in that there is such an explosion of new therapies within the last decade. There hasn’t been such momentum in any other cancer such as multiple myeloma. But, unfortunately, there are challenges such as language barriers and communication problems that overarching with all the different specialties. The geographic I had already mentioned in a previous discussion about the geographic barriers to participate in clinical trials, not meeting inclusion criteria, I think it takes an astute nurse or advanced practice provider or physician to now sequence the therapy.

So for example, they have new therapies such as BCMA-targeted drugs that are available through cellular therapy trials or bispecific antibody trials. And without getting too specific into the drugs, you need a specialist to be able to say, “Okay, if I give you this drug today, that will exclude you from a clinical trial that might be very innovative and promising in the future.”

So those are unique barriers to accessing clinical trials or standard therapies for that matter because of the plethora of therapies that are available. So getting in, having patients get in with a myeloma specialist, they might not see them on a regular basis, maybe employ telehealth techniques, see them once and then virtually connect, share information about what might be available. Those are ways that you can provide access to patients, caregivers, and others throughout their disease trajectory because they’re living longer than ever.

Dr. Nicole Rochester:

Which is a wonderful thing.

Dr. Beth Faiman:

Yes.


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What’s the Latest in Emerging Myeloma Research?

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

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

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

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Transcript:

Katherine:

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

Dr. Derman:

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

Katherine:

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

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

Dr. Derman:

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

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

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

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

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

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

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

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

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

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

What Experts Are Learning About the Hereditary Risk of Myeloma

What Experts Are Learning About the Hereditary Risk of Myeloma from Patient Empowerment Network on Vimeo.

Myeloma experts Dr. Irene Ghobrial and Dr. Betsy O’Donnell share research updates on predicting the risk of developing myeloma, both from inherited genetics as well as environmental factors.

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:

Is there any research on predicting hereditary risk of myeloma? 

Dr. Irene Ghobrial:

Yes, so part of the PROMISE study is trying to understand what is the risk of developing myeloma? So, we’re recruiting people who are either African American, because they have a three times higher chance of developing myeloma compared to the white population, as well as people who have a first degree family member with a plasma cell disorder. 

Or even any blood cancer because now we see that CLL and lymphoma and myeloma can actually come together. And we’re now doing something called whole genome sequencing of all of the DNA that you inherit from Mom or Dad called the germ line. Basically, we try to see did you inherit the gene from Mom or Dad that increases your risk to myeloma? 

Now, it’s not as high as something like BRCA1 mutation or 2 mutation, where if you have that, you’re high, high chance of developing breast cancer or ovarian cancer and so on. We probably have several factors that need to be put together. You inherit something and then the environment adds something, and then as we get older, we get the hit. 

Or you inherit something that changes your immune system, and that allows the plasma cells to start proliferating faster because they are reacting as an immune cell, and that allows the hit of myeloma to happen. And we’re working on that, and we would really encourage everyone who has a relative with myeloma, sign up on PROMISE study. 

Because that’s how we can get the answer. That’s how we can say it’s not because you are an African American or you’re white. It’s not because you have a first-degree family member or not. It’s because of this gene. So, taking away race, taking away all of those factors, taking away age and trying to go back to the biology. Is it a certain gene, is it the certain immune cell that makes us go to that risk? 

And then Dr. O’Donnell is really taking it to the next level. Now what is in the macro environment? So, we talked about what we inherit, but it’s like nurture and nature, right? So, nature is the genetics and then nurture, what do we eat? What do we change? Obesity, health, all of those things change our inflammation level and change our ability to basically prevent those myeloma cells from starting or from continuing to progress. And she can potentially talk about her work on microbiome, on the tiny bacteria that are in our body from what we eat. So, maybe, Betsy? 

Katherine Banwell:

Okay.  

Dr. Betsy O’Donnell:

Absolutely. Yes, so one of the things that particularly interests me is the effect of lifestyle on our risk of getting cancer. 

And specifically within plasma cell disorders, and I think there have been other cancers, breast cancer and colon cancer, where they’re a couple steps ahead of us just in understanding the influence of things like obesity and the gut microbiome. So, the specific bacteria that are within your intestinal tract. It makes a lot of sense in colon cancer, but we think that that’s not limited to diseases like that. We actually think that these microbiomes, which are influenced by the foods that you eat, may have a relationship with your immune system. And remember, myeloma is a cancer of the immune system. 

So, we’re all working together on our team here on a very scientific level to understand lifestyle influences and how they may cause or potentiate multiple myeloma. And so we’re excited to kind of bring this piece together. When you think about the spectrum of plasma cell disorders, not everybody goes on to myeloma, but a lot of people sit in these early precursor diseases, MGUS and early smoldering.  

And so are there things that people can do for themselves that might influence their gut microbiome, or if it’s the amount of body fat that we have that’s very involved in cell signaling? Can we modify those things, exercise more potentially, that will decrease our body inflammation levels or alter those pathways that have been set in process that, by altering them, may decrease the risk of going on to more advanced plasma cell disorders? 

Katherine Banwell:

That’s such great information.  

Expert Perspective: COVID Vaccines and Treatment for Myeloma Patients

Expert Perspective: COVID Vaccines and Treatment for Myeloma Patients from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Irene Ghobrial shares an update on COVID vaccines, treatment, and advice for myeloma patients on how to help protect themselves from the virus.

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.

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Transcript:

Katherine Banwell:

Many prominent doctors claim the COVID vaccines suppress the immune system. How can boosters be justified in an already immune deficient myeloma patient? 

Dr. Irene Ghobrial:

Yes, so we think that protecting yourself and preventing COVID infections is so essential and so important. 

Especially in a patient with myeloma and especially when you’re receiving therapy: daratumumab (Darzalex), bispecifics, CAR-T. We want to make sure everyone is protected from COVID infections, and they are real. They are serious, and they cause death in our patients. So, every step, not only getting the vaccine but also sometimes we give tixagevimab co-packaged with cilgavimab (Evusheld) to protect our patients and protect further problems and reinfection. 

Katherine Banwell:

Remind us, what that is, the Evusheld?  

Dr. Irene Ghobrial:

Oh. It’s an antibody to help us prevent the COVID infection, so as a prevention method rather than as a treatment method.  

The other thing that we think of is the immune system is already altered in myeloma. It’s even altered or changed even as early as MGUS and smoldering myeloma. So, when we’re walking around and thinking, “Oh, I have only a benign design of MGUS,” that’s not true. The immune system has already started to change as early as MGUS, and in many of us as we get older. 

So, we have to be more protective and we have to be more careful with our patients. But as we get to even myeloma, before we even treat it, before we use the drugs that kill plasma cells, good and bad plasma cells, which secrete antibodies that fight infections, we are already at risk for COVID infections. 

And then our drugs, unfortunately, don’t only kill the malignant or the bad plasma cells, they also have a small side effect of killing also your normal plasma cells, and these are the ones that make antibodies to fight infections. So, you are at risk, and you have to be very protective and careful with yourself. 

How Is Myeloma Treatment Response Measured?

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

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

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

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Transcript:

Katherine Banwell:

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

Dr. Betsy O’Donnell:

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

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

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

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

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

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

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

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

Which Myeloma Patients Are Candidates for CAR T-Cell Therapy?

Which Myeloma Patients Are Candidates for CAR T-Cell Therapy? from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Omar Nadeem discusses which patients are most appropriate for CAR T-cell therapy and explains cytokine release syndrome (CRS), which may arise following this treatment approach.

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

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Transcript:

Katherine Banwell:  

“How is it determined as to which patients might be the best candidates for clinical trial CAR T-cell treatment?”  

Dr. Omar Nadeem:  

So, CAR T-cell therapy is already approved. It’s FDA-approved for patients that have had four or more prior lines of myeloma therapy. So, when we think about a patient coming to us for that particular treatment that have relapsed myeloma, we’re always looking to see how much of the previous therapy they had. 

Whether they meet the indication, the labeled indication for that particular product. And then now, as we’ve discussed today, we’re studying this CAR T-cell therapy in various different phases of myeloma. Earlier lines of therapy, even thinking about studying it in high-risk smoldering myeloma, right? And then kind of looking about how we can best study this therapy in so many different phases. 

So, it all depends on where a patient is in their disease state, and then we kind of look to see whether a commercial approved CAR-T product makes sense for them, or we think about one of our several relapse CAR T-cell trials that are looking at BCMA target, which is what the approved one is, but also looking at newer targets like GPRC5D that we’ve brought up before. 

So, it encompasses a lot of different things, that question, but I think in terms of the candidacy of the patient itself, we do know that these CAR T-cell therapies have some toxicity, so we have to then weigh in terms of what medical problems they have whether they’ll be able to tolerate what the majority of patients with CAR T-cell therapy get, which is this syndrome called cytokine release syndrome, where patients will get a fever. 

And in some cases have changes in their blood pressure or oxygen levels. We have to make sure that the patient’s body can handle that. I will say we’ve gotten better and better at managing a lot of toxicities as it comes to CAR T-cell therapy. When this was first approved, it was all pretty new, but now what we’re learning is if patients are developing a fever, which the majority do, we’re intervening earlier and earlier to prevent them from getting sicker. 

So, these are things we’ve learned now, and the majority of patients get through CAR T-cell therapy toxicity period much better than they did when it was first approved. 

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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How Do Test Results Impact Myeloma Treatment Options?


Transcript:

Katherine Banwell:

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

Dr. Irene Ghobrial:

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

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

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

Katherine Banwell:

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

Dr. Irene Ghobrial:

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

Katherine Banwell:

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

Dr. Irene Ghobrial:

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

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

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

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

Katherine Banwell:

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

Dr. Betsy O’Donnell:

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

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

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

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

Katherine Banwell:

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

Dr. Betsy O’Donnell:

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

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

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

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

How Are Patients on Myeloma Maintenance Therapy Monitored?

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

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

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

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Transcript:

Katherine Banwell:

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

Dr. Omar Nadeem:

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

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

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

How Is Research Advancing Myeloma Treatment and Care?

How Is Research Advancing Myeloma Treatment and Care? from Patient Empowerment Network on Vimeo.

A panel of myeloma experts, including Drs. Omar Nadeem, Irene Ghobrial, and Betsy O’Donnell, discuss how clinical trials advance myeloma research and share an update on promising therapies in development.

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

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:

Where do clinical trials fit into a patient’s treatment plan? 

Dr. Omar Nadeem:

Yes. So, clinical trials as a term, a lot of times patients have a lot of questions about what that means. There’s a lot of misconceptions, I would say.  

Sometimes patients think they will get either a placebo and they won’t get the adequate treatment, or that they may not get the right treatment, right, because they’re taking a chance going on a clinical trial. It’s actually the opposite. So, all the trials are really designed to improve upon what we already know works in a particular disease, right? So, when we think about trials let’s say in relapsed myeloma, where the patient has already had some of the approved therapies, we’re looking at the most promising new therapies that have shown efficacy either in the lab or first in human studies and then moving them through the different phases and studying them in more and more patients.  

And that’s how all these drugs get started, right? So, they all get started at that point and then make their way to earlier lines of therapy.  

Then you’re trying to answer different questions as part of clinical trials. So, which one of these therapies can I combine, for example. Which ones can I omit, which ones – so, they’re all sort of getting the standard therapy and getting something either added on top of it or removed, depending on what the question that we’re asking. 

And then in the world that we currently live in with precursor plasma cell disorders, as Dr. Ghobrial mentioned, we have lots of patients that are at high risk of developing multiple myeloma in their lifetime, and that could be in a few years to a decade. And a lot of these therapies are so effective, and we’re now trying to really study some of these rationally in that patient population, so that’s a very different clinical trial, for example, than what I described earlier.  

So, it really depends on what you’re trying to achieve and where you are in the phase of your disease. 

Katherine Banwell:

This next question is open to all of you. Are there therapies in development that are showing promise for patients with myeloma? Dr. O’Donnell, let’s start with you.  

Dr. Betsy O’Donnell:

Yes. So, I think we are so fortunate in multiple myeloma to have so much interest in our disease and so many great drugs developed. So, as Dr. Nadeem was discussing, CAR-T cells are an immunotherapy, the ones that are approved now, we actually are fortunate to have two CAR-T cells approved, target something very specific called B-cell maturation antigen.  

We’re now seeing the next generation where we’re looking at other targets on the same cancer cell, that plasma cell, so those are evolving. 

Same thing is true in the bispecific antibody space. Again, those target BCMA now, but we have newer bispecifics who look at alternate targets, and really what this does is it gives us different ways of approaching the cancer cell, particularly as you relapse through disease.  

Dr. Irene Ghobrial:

I would probably say we’re also getting into targeted therapies and more of personalized, so if you have an 11;14 translocation, venetoclax (Venclexta) would be an amazing drug for that. And the more we can say my own personal myeloma, what’s the best treatment for me, that’s how we’re trying to do it. So, it may not be exactly precision medicine, but we’re getting closer and closer to precision medicine of my myeloma, my specific drugs. And even if people have a 17p deletion, then we would say let’s think of that immunotherapy.  

It is truly a renaissance for us, and we’re starting to get into trispecifics, into off-the-shelf CAR-T, into so many new things. Into two different antigens that are expressed for the CAR-Ts. I mean, we are really beginning the era of immunotherapy, and we’re excited to see how much we can go into that because it will completely change myeloma, and hopefully we will cure many patients. We think we have already amazing drugs. It’s a matter of when to use them and who is the right person for this right drug. 

Katherine:

What are you hopeful about the future of care for myeloma patients? Dr. Ghobrial, do you want to start? 

Dr. Irene Ghobrial:

I’m hopeful that we truly cure myeloma, and no one should ever develop end organ damage. 

We should identify it early and treat it early, and no one should ever come in being diagnosed with multiple myeloma. 

Katherine Banwell:

Okay. Dr. Nadeem? 

Dr. Omar Nadeem:

Yes, I think I definitely agree with what Irene said, and really having a more thoughtful approach to each individual myeloma patient. As I mentioned earlier, we have so many available therapies. I want to be able to know exactly which patients need which path in terms of treatment, and which ones we can maybe de-escalate therapy, right? So, thinking about which patients do well and maybe can get away with not being on continuous therapy, and those that absolutely need it. Identifying them better to give them the best therapy. 

Katherine Banwell:

Dr. O’Donnell, do you have anything to add? 

Dr. Betsy O’Donnell:

I think we all share a common goal, which is cure, and for those who we can’t cure yet, I think really working on making the experience as good as it possibly can be and focusing on the factors that we can control and optimizing those, both for patients and their caregivers who are in this journey together with the patient.  

What Are Currently Available Myeloma Treatments?

What Are Currently Available Myeloma Treatments? from Patient Empowerment Network on Vimeo.

Dr. Omar Nadeem reviews myeloma treatment classes, including immunomodulatory therapies, proteasome inhibitors, and monoclonal antibodies. Dr. Nadeem also discusses how combining these therapies has boosted the effectiveness of myeloma treatment.

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

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How Is Research Advancing Myeloma Treatment and Care?


Transcript:

Katherine Banwell:

Dr. Nadeem, what types of myeloma treatment classes are currently available?  

Dr. Omar Nadeem:

Yes. So, we started over three decades ago plus with just having basically steroid medications and some older chemotherapy drugs that weren’t very targeted at all, and that was basically all we had up until about a little over 20 years ago, where immunomodulatory drugs were first discovered to be effective in multiple myeloma, and that included thalidomide (Contergan or Thalomid) and now a commonly used agent called lenalidomide, or Revlimid.  

After that, we had a next class of medications approved called proteasome inhibitors that work differently than the immunomodulatory drugs, and then we combined all of these therapies about a decade plus ago and showed that that was better than anything else that we were doing before that. So, combining the steroids with the immunomodulatory drugs and proteasome inhibitors became the standard of care. 

And then we had the next class of drugs approved in 2015 called monoclonal antibodies, and that’s the first time we have monoclonal antibodies approved for myeloma, and it first started in patients that had relapsed myeloma, and then they made it all the way up to front line therapy with a drug in particular called daratumumab (Darzalex).  

And now what we’re going is entering an era of combining all four of these therapies, just like we did 10 years ago with three drugs, and showing that combining four drugs is actually better than three. And the important thing there is that it’s not necessarily adding cumulative toxicity. These are targeted therapies; they all work differently, but they all work really well together. So, now combining these agents has allowed us to really treat the disease effectively and allow for patients to tolerate the therapies.  

And then over the last couple of years, we’ve now entered kind of the next renaissance in myeloma where you have immunotherapies, and these are sort of true immunotherapies, in some cases taking the patient’s own T cells and then genetically modifying them to recognize myeloma cells and putting them back into patients. This is called CAR T-cell therapy, and that’s now approved for patients with multiple myeloma.  

And that again, just like the previous drug, sits in patients that have – you know, at a space where patients have had multiple relapses. But we’re now studying that earlier and earlier, and that along with another class of drugs called bispecific antibodies that also use your T cells via a different mechanism. A lot of exciting things going on, and we keep adding to the available agents for this disease.  

Understanding Personalized Medicine for Myeloma

Understanding Personalized Medicine for Myeloma from Patient Empowerment Network on Vimeo.

Myeloma experts Dr. Omar Nadeem and Dr. Betsy O’Donnell discuss the personalized approach to treating myeloma and the factors that are considered when making care decisions.

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

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

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How Is Research Advancing Myeloma Treatment and Care?


Transcript:

Katherine Banwell:

Dr. Nadeem, as we begin our treatment discussion, would you define personalized medicine as it relates to myeloma care? 

Dr. Omar Nadeem:

Yes. I think we’re getting better and better at really having a personalized treatment plan for each individual patient with multiple myeloma. I think Dr. O’Donnell defined before, we are identifying some of the markers where we have targeted therapy for, and we hope with time we’ll discover more and more targets that can truly lead to personalized medicine for individual patients. 

Right now, though, we have a lot of approved therapies for multiple myeloma, and that list is getting longer and longer basically every month, it seems, nowadays. So, when we have so many tools in our toolkit, we then have to figure out, well, which strategy works for which patient? And the fact that we have effective therapies, we’re able to tailor how much of one particular therapy a patient may benefit from. So, some of the decisions that come into play is which medication should I combine for this patient which will lead to obviously disease eradication? 

And then also, how much do I need to intensify that treatment? Do we need to think about doing a stem cell transplant or not? Yes or no?  

There are lot of pros and cons, right? So, it’s a very personalized decision that we have, looking at the disease factors, but also a lot of personal factors because transplant interrupts life, and then we have to make sure that that fits with that particular patient’s lifestyle.  

And then we talk about maintenance therapy. You know, that’s the therapy that is designed to kind of keep the disease away usually for many, many years for the majority of patients.   

But what does that look like, right? Does that include just pills? Is it going to be shots plus pills? Is it going to be a combination, etcetera? So, we have all the discussions at each phase of myeloma, and we discuss with them about what the pros and cons are and how that may fit into their particular lifestyle. 

Katherine Banwell:

Dr. O’Donnell, what factors do you consider when choosing a treatment approach? 

Dr. Betsy O’Donnell:

So, I think you’ve heard from all of us that we really try to have an individualized approach. When we’re talking about multiple myeloma, one of the main factors that I think about is really kind of the overall wellness of the patient. Historically, we had different categories of transplant eligible, transplant ineligible. 

And so that can influence some of the decisions. Really it comes down to what is it the person’s performance does? How well are they doing in their day-to-day life? And that really can dictate the intensity of the therapy. We know that age is just a number, it really is, so there are factors beyond that. What other medical problems do people have? What are the specifics of how well their kidneys are working? 

And so the biggest thing that we can work with is the dose. In fact, we’ve had work that shows that using lower doses from the get-go in older patients allows almost identical outcomes, but really gives patients a tailored dose to where they are at that juncture in their life.  

And so remember, myeloma is much more like a marathon, and so you have to set out at a pace that can be sustained. We treat people continuously. There’s an induction phase where we use a multiple drug combination, but beyond that, as Dr. Nadeem just said, they go on to maintenance, and that maintenance is indefinite. And so you have to set out at a pace or at a dose that you can sustain. 

Different medications have different toxicity profiles, so if someone had, let’s say, cardiac or heart issues, we might steer away from some medications that may exacerbate those. So, every decision is individualized. It’s based on who the patient is, where they are in their life, what other medical problems they have, and what we think they will do best with over time, not just in a short timeframe.