Tag Archive for: bortezomib

Elevate | What Role Can YOU Play in Your Myeloma Treatment and Care?

How can you elevate your overall myeloma care and treatment? Myeloma expert Dr. Sikander Ailawadhi discusses advances in myeloma care, the importance of patient participation in myeloma treatment decisions, and shares key advice and resources for self-advocacy.
 
Dr. Sikander Ailawadhi is a hematologist and oncologist specializing in myeloma at Mayo Clinic in Jacksonville, Florida. Learn more about Dr. Ailawadhi.

Related Resources:

Self-Advocacy in Myeloma Care | Advice From an Expert

Self-Advocacy in Myeloma Care | Advice From an Expert 

Myeloma Combination Therapy _ What Patients Should Know

Myeloma Combination Therapy | What Patients Should Know 

What Should You Know About Emerging Myeloma Treatment Options? 

Transcript:

Katherine:

Hello and welcome. I’m your host, Katherine Banwell. It’s no secret that the quality of care that patients receive can vary depending on a number of factors and patients who are educated about their condition and involved in their care may have improved outcomes. That’s why the Patient Empowerment Network developed the Elevate Series, which aims to help patients and care partners be informed about their disease and more confident participating in conversations with their healthcare team.

In today’s program, we’re going to hear from an expert to learn more about myeloma and hear tips and advice for accessing better overall care. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Well, let’s meet our guest today. Joining us is Dr. Sikandar Ailawadhi. Dr. Ailawadhi, welcome. Would you please introduce yourself?

Dr. Ailawadhi:

Yes. Thanks a lot, Katherine. Thanks for this opportunity. To all our viewers, listeners, I’m Sikandar Ailawadhi. I’m one of the hematologists oncologists at Mayo Clinic in Jacksonville, Florida. So, at this Jacksonville, Florida site of Mayo, I lead our myeloma group, and we have a very comprehensive program with inpatient outpatient treatment and lots of clinical trials, cell therapy, et cetera. I look forward to the discussion.  

Katherine:

Well, thank you so much for joining us today. I know you’re a busy man. I’d like to start by discussing your role as a researcher. You’re on the front lines of advancements in the myeloma field. So, what led you here, and why is it so important to you?   

Dr. Ailawadhi:

Yeah. So, Katherine, thanks for asking that question because before jumping into the disease state and clinical trials and data, et cetera, I think it’s important for all of us to keep in mind what kind of brought us here or what kind of keeps driving us further. So, I think for me, the decision to come to the field of multiple myeloma was very strongly influenced by my mentors.

My mentor who shaped my career and also got me interested in this area. I think during my training, it was the time that newer drugs were just beginning to come about. So, the field of myeloma was just beginning to change. And since then, obviously, there have been lots of advancements, lots of research, clinical trials, new drugs, so that the outlook for not only the myeloma patients has improved quite a bit.   

But also, for physicians, researchers, us academicians who work in this field, the opportunities are much, much more. And because I trained at a large academic center, I – and again, with working with my mentor, I got so interested in the clinical research because frankly giving the available drugs is one thing but being at that cutting edge where you can bring newer drugs to life, newer drugs to our patients’ lives, that was what was most important for me and is the driving force for my work today.  

Katherine:

Thank you for that explanation, Dr. Ailawadhi. I appreciate it. So, when it comes to choosing therapy for myeloma, it’s important to work with your healthcare team to identify what might be best for you. How would you define shared decision-making and why is this so critical to properly managing life with myeloma?  

Dr. Ailawadhi:

Excellent question, Katherine. Shared decision-making or a process in which the physician, the health care team, and the patient, their caregivers, everybody comes together, shared, to make a decision that we feel is in the best interest for that patient at that time. That is the whole concept.  

Whenever we think about treatment decisions, in our mind, the three main components that have to be considered every single time. Not just newly diagnosed or relapsed or third line or whatever, every single time a treatment decision has been taken, we must consider patient-related factors. What is their preference? What are their goals? Do they have caregiver support? How far do they live? Do they want IV? Pills? Any side effects that are there?  

Comorbidities? Other issues? Financial conditions? Everything comes into play, patient-related factors. Then, there are disease-related factors. How fast is the disease growing? Is this new? Is this old disease, high-risk, low-risk, or standard risk? Or what has been given before, et cetera. So, patient and disease-related. And the number three is the treatment-related factors. What is being considered for the patient? What are the ins and outs, pros, and cons?   

All of this has to be laid out in front of the patient and preferably also their caregiver if the patient has someone who they can share their decision with.  

And when we put all of that in the mix, we come up with a decision which is hopefully in the patient’s best interest. They are more likely to go through with it. They are informed. They are involved in their care. And then, hopefully, if the patient starts on a treatment that they are interested in, knowledgeable about, and committed to, we’ll be able to keep the patient on that longer term and get the best benefit out of it.   

So, in my mind, the main reason for shared decision-making is to make sure my patient is committed to that treatment. They understand that treatment. And we make this kind of bond between us as clinicians and our teams and the patient and their home team, their family team, their caregiver team so that everybody is working together with a singular goal. Right treatment for the right patient at the right time because it must be patient-centric, not research or clinician, or drug-centric. 

Katherine:

Yeah. Okay. That’s good advice. What are myeloma treatment goals, and how are they determined?   

Dr. Ailawadhi:

So, I think the myeloma treatment goals can be very different depending on what vantage points you’re looking from. My treatment goal is to provide the best treatment for my patient that has least side effects, gets a deep control, and my patient’s able to live long with a good quality of life. Okay. But that’s my goal.  I need to figure out what my patient’s goals are, and sometimes our patient’s goals are very different. A patient’s goal might be that they want to really avoid side effects. Well, they want to live, lead their quality of life, and keep traveling. And this happens on a day-to-day basis.  

Just the other day, one of the patients said, “Well, I really want to keep driving around in my RV with my wife, because that is what we had wanted to do at this point of our life. What can you do to help me control my disease, but keep me driving my RV?” And we literally had to figure out where all they were traveling. We identified clinics close to them and connected with physicians so that they could continue their treatment wherever they were. So, the patient’s goals are very important, and in fact, I would say they are paramount. So, understanding what the patient wants. They may be wanting to control pain. They may be wanting to just live longer.  

They may be wanting to delay treatment so that they could watch their daughter’s soccer game. I’m just saying that the goals can be very different. It is important to lay them out. Every time you’re making a treatment decision, the goals should be laid out into short-, mid-, and long-term goals. I should bring my goals to the discussion. The patient should bring their goals to the discussion, and we come up with whatever is the best answer for them that suits them.  

Katherine:

So, you’re trying to maintain an open dialogue, an open line of communication, yeah.  

Dr. Ailawadhi:

Absolutely.  

Katherine:

What sort of tests should be done following a myeloma diagnosis?   

Dr. Ailawadhi:

Generally, when myeloma is suspected, we need to know what the basic blood counts are, something that is called a CBC, complete blood count. We’re looking for anemia, low white blood cells, low clotting cells, or platelets. We want to do serum chemistries or blood chemistries, looking for kidney function, liver function, electrolytes, calcium, et cetera.   

Then, we want to do some kind of an imaging of the body. Generally, routine X-rays are no longer done, and the most preferred is a PET-CT scan, a PET scan. We do PET-MRIs frequently. So, there are different tests available, but you want a good test to know what’s the state of bones and presence of any lesions or tumors. And then, the important question comes is doing a bone marrow biopsy.   

The reason for doing a bone marrow biopsy, and even if somebody has had a biopsy done from a compression fracture, et cetera, that diagnosed myeloma, a bone marrow biopsy still should be done. It gives us a lot of pieces of information.  

It tells us what is the percentage of plasma cells in the bone marrow. So, what is the disease burden we are starting with? Secondly, that bone marrow biopsy specimen can be sent for what is called a FISH testing, which is fluorescent in situ hybridization.  

It is basically looking for any mutations in the cancer cells. Based on those mutations, myeloma can be classified into standard or high-risk myeloma. And sometimes our treatment choices are differed based on whether somebody is standard or high-risk. So, blood work, basic counts – and I skipped over one of the things. Right after chemistries, I wanted to add also are myeloma markers.  

There are typically three lab tests of myeloma markers. One is called protein electrophoresis. It can be run in blood and urine. Ideally, it should be run in both. One is immunoglobulin levels, which gives us the level of IgG, IgA, IgM, et cetera. And the third one is serum-free light chains, which is kappa and lambda light chains. Neither one – none of these tests eliminates the needs for the other.

So, everybody, in the beginning, should have complete blood count, blood chemistries, SPEP or serum protein electrophoresis, urine electrophoresis, immunoglobulins, light chains, imaging, and then a bone marrow. This completes the workup. Then, based on that, the treatment can be determined.  

Katherine:

Well, you mentioned lab work. How often should tests and blood work be done?   

Dr. Ailawadhi:

Good question. Very, very important question because we see very frequently that the patients come in, they’re getting treatment somewhere, and every single time the patient steps foot in the door of that institution or wherever they’re going, they got a blood draw. That’s how they start their day. It’s needed more frequently in the beginning but needed less frequently later on.

Generally, the myeloma markers, those protein electrophoresis, immunoglobulins, light chains, they are frequently done just about every month. Generally, in myeloma, one month, three to four weeks is one cycle. So, at the beginning of every cycle, you want to know how good your response was. So, the myeloma markers once a month.  

The blood counts and chemistries in the first month, first one to two months, they can be done every other week or so just to make sure counts are fine, no need for transfusions, kidney/liver is okay, et cetera. But after the first couple of months, when the body is used to the drugs when the patient is settled with the treatment, frankly, once-a-month labs are good enough. We don’t really need labs on every single treatment visit. Because the other thing that happens is some of these drugs can lower the blood counts normally during treatment, but they have a rest period at the end of the cycle when the counts recover.

So, if somebody does labs in the middle of the cycle when the counts are expected to be down but not an issue, treatments are stopped, and growth factors are given. And this is done, but that is not really necessary. So, first couple of one to two cycles, maybe every other week to make sure counts are okay. Myeloma markers monthly, but after the first couple of months when things are settled, once a month should be sufficient.   

Katherine:

Okay. What questions should patients be asking about their test results?   

Dr. Ailawadhi:

Yeah. Very, very, very important. In fact, whenever I’m speaking in a patient caregiver symposium or anything, I spend a lot of time on these test results because frankly, a lot of times it sounds like jargon and the people talk about, “Oh, my ratio is going up,” or the doctor is saying, “Hey, your immunoglobulins are normal. You’re in remission.” But so, I think the patients need to understand and ask from their doctors, “What is my marker of the disease that you will be following?” And I’ll tell you that immunoglobulins, that IgG or IgA level, is nearly never the marker. It’s either M spike or light chains, generally one of those.  

So, the patients need to understand what is their marker. They also need to know what did their bone marrow show. What was the percentage and what was the FISH result or cytogenetic result? I think other than the tests, I will also add the patients need to ask their doctor a lot of these questions that you’re asking me. How frequently are the labs going to be done? Why is it important? Why was a certain treatment selected? What is the expected outcome? What are the chances that I can go into remission? How long does the intense treatment stay?  

When does it go to some kind of a maintenance? Et cetera, et cetera. Basically, you want to understand everything about the disease and its treatment. It is overwhelming. This is a lot of information. A lot of times the patients may say, “Well, I got a diagnosis. I got a treatment started. I just need to move on.”  That’s right. But once you spend all that time initially understanding your diagnosis and the treatment and the disease, it’ll make the rest of the journey much, much easier.  

Katherine:

That’s really helpful as we drill down a little further. What are the types of treatments available for people with myeloma?   

Dr. Ailawadhi:

So, myeloma has a lot of treatments available. We can classify these treatments into different classes of drugs, or we can classify the treatment as early lines or late lines of therapy. Or we can classify these treatments into cellular therapy or targeted therapy or chemotherapy. There are ways of classifying it.  What I would suggest is we should think about classes of drugs. We have something called proteasome inhibitors. That class has three drugs FDA-approved. We have something called immunomodulatory drugs. That class has three drugs also approved, but generally, we use two.   

Then, there are something called monoclonal antibodies. There are three drugs approved there as well.   

There are cellular therapies or CAR T-cell therapy. There are two of them approved. There is also a stem cell transplant that is used as a part of treatment sometimes but is different from CAR T. Then, there are other immunotherapy, something called T-cell engagers, in which also there are three drugs approved. In fact, as I’m saying to you, I’m trying to think…yeah, wow. Every class has three drugs. That’s so weird. And then, there are some other classes of drugs. There is something called exporting inhibitors. There is a drug there. All said and done, there are these different classes of drugs.  

There are some guiding principles for myeloma treatment. Generally, three to four drug combinations or regimens are better than two drugs. So, a patient should be in the initial therapy or later lines. Also, preferably be getting a three-drug combo. And I forgot to mention steroids, which are an important part of every regimen in myeloma, almost every regimen. So, three drugs or four drugs are better than two. That’s important to keep in mind. Longer durations of treatment are generally considered better. We should not tinker with the regimen’s recipe too soon. As long as the patient is tolerating for a longer duration before making any major changes like maintenance.    

Generally, maintenance in myeloma is not a response-assessed thing like, “Oh, you’ve responded in two months. We should go to maintenance.” Generally, in myeloma, maintenance transition is a time-dependent thing. Okay, you’ve had six or nine months or 12 months. We can go to maintenance, sort of a thing. So, even if somebody has responded, they may need the same treatment for a longer period of time to keep the disease quiet.  

And so, I think these are the different categories of drugs. We pick and choose from different categories to combine and make a regimen. The CAR T-cell therapy, the two CAR Ts that are approved, or the three T-cell engagers that are approved, they are all currently used as single agents. They are not combined with anything, not even with steroids. 

Katherine:

Yeah, I see. How do clinical trials fit into a treatment plan?   

Dr. Ailawadhi:

Okay, that’s an extremely important question, and you’re asking it from a person in my clinic about two-thirds of the patients who are on treatment at any given time are on clinical trials. So, I am very heavily, I shouldn’t say biased, but a proponent of clinical trials. In my opinion, clinical trials are a part and parcel of treatment for every single patient. In fact, when you look at the NCCN guidelines, which are National Comprehensive Cancer Network, which is large institutions across the country, and they make guidelines for all cancers, it is mentioned in every single setting that clinical trials should always be considered.  

So, I personally feel that whenever the patient is coming up with a treatment decision, we talked about shared decision-making in the beginning, it’s important for them to ask at every single juncture, “Do you have any clinical trials available for me? 

And if you don’t have any clinical trials available, are there any clinical trials that I should consider, even if it means going to a different place and getting an opinion?” I know logistically it’s challenging, but we should at least know our options. So, in my opinion, clinical trials should be considered at every single juncture, because that is how patients get access to either a new drug, a new treatment, or a different way of using the current drugs, which might actually improve upon their current state. So, everybody all the time should consider clinical trials.   

Katherine:

That’s great information, Dr. Ailawadhi. Thank you for that. I’d like to add that if you’re interested in learning more about emerging treatments, such as CAR T-cell therapy, PEN has a number of resources available for you, and you can find these at powerfulpatients.org/myeloma, or by scanning the QR code on your screen.   

So, the symptoms of myeloma, as well as the side effects of certain medications, can vary greatly among those being treated. How do you approach symptom management with your patients?   

Dr. Ailawadhi:

It is extremely important that we focus on the symptoms, whether it’s coming from the disease or it’s coming from the treatment. Because frankly, if a person is responding to the treatment, you want them to stay on the treatment for a longer duration of time, so the disease can stay controlled. 

If we don’t handle the symptoms from the treatment or the side effects that are happening or if the disease is causing too many symptoms, it is more likely that either we’ll start cutting down the drug too much or stopping the treatment, et cetera, and then the disease just comes back. In some cases, that is necessary, but generally we would like to modulate the treatment or address the symptoms.  

So, one important piece that we should do, or at least we try to do over here, is that every single time that we talk to the patient for any of the visits – while there is enough time spent on, “Well, these are your labs, your diseases responding markers, SPEP, and M spike, and light chain,” and all that stuff – we spend a lot of time asking about symptoms.  

It is, I understand, challenging to cover everything, but to familiarize what drugs cause what kind of symptoms, and at least making sure that we ask those from the patient. For example, IMiDs like lenalidomide (Revlimid) can cause some diarrhea, can cause fatigue, can cause sleepiness. Well, I must ask about diarrhea from all my lenalidomide patients.  

Bortezomib (Velcade) can cause neuropathy. It can give rise to shingles. I must ask my patients for every bortezomib-treated patient. “Hey, do you have any neuropathy numbness, or tingling?  

Are you taking your medication to prevent shingles, et cetera?” I’m just saying we may not be able to do a comprehensive review of every single symptom from every single patient, but whatever the target side effects are important to know every single time. We educate the patients about these side effects so that they are aware of them, and they can report these side effects. And then, if the side effects are happening, any symptoms are happening, then is it to the point that we need to stop the treatment?  

Frequently, we do take drug holidays for a few weeks just to make sure, okay, we know is it coming from the drug or the disease? And every now and then, we realize, well, the drug was not even causing the symptom, because we stopped it, and the symptom stayed. Or so then, why stop the drug? There’s no point stopping it if I can’t control the symptom. So, understanding whether it’s coming from disease or drug or something else, addressing them, making the changes appropriately to lower the dose, space them out, et cetera. All of that is done. And of course, like I said, importantly, educating the patient is so very important. I’ll add one quick thing. We focus on the drug-related effects.  

As you rightly mentioned, Katherine, the disease itself can cause a lot of symptoms. So, generally, when I see a new myeloma patient, in the first couple of visits, we’ve done all the testing, we’ve discussed the treatment, and we’ve addressed some of the basic symptoms like pain, for example. That is big in myeloma.

But then, when the patient has started treatment, generally within the first two months, the focus that our clinic has is we need to control any side effects, and we need to address any symptoms that are being left over from the disease. And that’s when we start referring patients to interventional radiology for any bone procedures or palliative care for pain control or neurology for neuropathy, whatever so that we are controlling all the symptoms.  

And that’s when we hopefully get the patient as close to their baseline as possible.   

Katherine:

I would like to talk more about self-advocacy, Dr. Ailawadhi, managing the worry associated with a diagnosis, concerns about relapse, side effects. It can lead to emotional symptoms like anxiety and fear for many. So, why is it important for patients to share any worries they’re having with their healthcare team?   

Dr. Ailawadhi:

Yes. Extremely important. See, nobody’s thinking, “Okay, I’m going to have cancer today.” Nobody’s prepared for it ever. Cancer is always a diagnosis that comes out of the blue, blindsides us, and then suddenly we have to change the rest of our life because of it.  Not only our life, our caregiver’s life, family’s life, everything changes.  

So, it is okay to admit that it is difficult. It is okay to admit that we need help. And, Katherine, I like your kind of the use of the word, self-advocacy, although I want to qualify it.  

A lot of times we say patients got to be their own advocates. But if a patient doesn’t know what to ask, they’re going to be lost. My thought is it is okay to – the first and foremost that a patient or their caregiver can do is please report your symptoms or how you’re feeling. And those symptoms could be physical, those could be psychological. 

Please report what are you feeling, what are the symptoms. On a drug, what are the side effects, et cetera, so that your healthcare team can try to address them. Don’t ever assume, “I am on chemotherapy. I should have diarrhea.” No. Don’t think, “I’m on chemotherapy. Other patients outside in the waiting room look sicker than I. I feel embarrassed to ask a question.”  

We hear this so many times. A lot of patients will say, “I feel embarrassed to ask that I’m going through this symptom, because I see sicker people outside.” Yeah, but know when I’m with you as a patient, you are it. I’m not thinking about anybody else. And I don’t want anybody else’s decision to obscure or cloud our relationship at that visit. Please report your symptoms. Please ask for help.  To me, that is good enough self-advocacy. Self-advocacy is not saying, “I should get this treatment, not that treatment.” But self-advocacy could mean, are there clinical trial options?  I know I live far away from a large center. Could I get a tele-visit with a large center? Could I get a second opinion from someone? Those are all very, very reasonable questions, and by asking those questions, a patient is advocating for themselves.  

Katherine:

As you alluded, there’s a whole healthcare team working with each patient, and there’ll be people on that team who can help support a patient’s emotional needs. So, one thing that’s on the mind of many viewers is the financial aspect of care. And you mentioned that earlier everyone’s situation is different, of course, but where can patients turn if they need resources for financial support

Dr. Ailawadhi:

Very important question. I can tell you every day when I come into my office, my nurse has a stack of documents ready for my signature. Every single day. Today, there was only one, but there could be different numbers. And these are generally from foundations from diagnosis confirmations, et cetera. Things that we are filling on and signing on behalf of our patients so that they are able to receive resources, whether it’s from a pharmaceutical manufacturer, a foundation, or society that has funding available, et cetera. I should start by saying, Katherine – and I feel embarrassed to admit this, but I should start by saying, I may not have all the answers for my patient during that visit.   

But I think the very important piece where we can start is asking the patient, “Is this causing any financial strain on you?” As I mentioned earlier, we don’t think about, “Oh, I’m going to have cancer today. Let me prepare for that.” Or “I’m going to have cancer five years down the road. Let me prepare for that.” We’re not always ready for this. It’s okay. It’s important for me to ask if there is a problem, and it’s important for the patient to admit there’s a problem or say, “Well, I’m having difficulty with copayments.” And whatever may be difficult for one may be okay for the other. So, I shouldn’t assume. So, that discussion must happen.

Generally, in our setup, what happens is if the patient brings up a concern, if I identify a concern, or if we think something may be going on, but we’re not very sure about it, we tend to bring in our social workers. The social workers are typically the ones who are able to do that discussion with the patient, talk about what are the resources available. What are the foundations that we can apply to? We have patient navigators who can do the similar things. So, the patient navigator, social worker, there are different individuals who will be able to provide much more granular information. I also strongly suggest patients to join support groups.

There are lots of resources, which I may not be aware of during our visit with a patient, but I can connect to the social worker, their patient navigators, and online support. 

Katherine:

Thank you for that. It’s great advice. As we close the program, what would you like to leave the audience with? Why are you hopeful?   

Dr. Ailawadhi:

First of all, I should admit, yes, I’m very, very hopeful for myeloma. I started my work with myeloma or my time working in this field in somewhere around the year 2000 or around that year. In the early 2000s, the average survival of a myeloma patient despite treatment was about two to three years.

Today, while national data is suggesting somewhere in the vicinity of 10ish years, give or take, all of us who are myeloma-focused physicians and have specialized centers that we work in, we have many patients who are living in excess of 10 years and pushing the envelope. In fact, my longest survivor is now maybe 34, 35 years with myeloma, and she’s not even been on treatment for a few years.  

This is what gives me hope. That it’s not only that patients are living longer, more and more patients are living with less disease burden, better quality of life, and in a lot of cases, not even on a treatment. Our myeloma world is now going from everybody should be treated forever and ever to there are many a clinical trial that are testing the hypothesis of, “Can we stop treatment? Who needs to be treated? Could we be getting closer to that elusive cure that we all are looking for in myeloma?”

So, to me, the hope is newer drugs that are better tolerated, providing better quality of life for patients. And in a lot of cases, the patients are not even on treatment. That is where we think we are making a change and making a difference. And you had started by asking me, “What is the driving force?” That to me is the driving force of why we get excited to come to work every morning, because we know that we can help someone else, and we can learn something new.

Katherine:

That’s very promising, Dr. Ailawadhi. Thanks so much for taking the time to join us today.  

Dr. Ailawadhi:

Absolutely. Thanks a lot for this opportunity.   

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 being with us today.

Next Generation Myeloma Treatment Options

Next Generation Myeloma Treatment Options from Patient Empowerment Network on Vimeo.

What new myeloma therapies are showing promise? Myeloma expert Dr. Omar Nadeem shares an update on emerging myeloma treatment research, including CELMoDs, and shares advice for a having a treatment plan roadmap. 

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.

Download Resource Guide

See More from Evolve Myeloma

Related Resources:

Personalized Medicine for Myeloma Treatment | What Patients Should Know

Personalized Medicine for Myeloma Treatment | What Patients Should Know

Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023 

What Should Myeloma Patients Ask About Developing Research

What Should Myeloma Patients Ask About Developing Research?

Transcript:

Katherine:

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. 

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

Evolving Myeloma Treatment Options: How You Can Access Cutting-Edge Care from Patient Empowerment Network on Vimeo.

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.

Download Resource Guide

See More from Evolve Myeloma

Related Resources:

What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

What Is the Role of Bispecific Antibody Therapy in the Future of Myeloma Care?

Questions to Ask Your Doctor About CAR T-Cell Therapy

Questions to Ask Your Doctor About CAR T-Cell Therapy

Considering CAR T-Cell Therapy for Myeloma_ Key Questions to Ask Your Doctor

Considering CAR T-Cell Therapy for Myeloma? Key Questions to Ask Your Doctor 

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: Thrive | Considering CAR T-Cell Therapy for Myeloma? What You Should Know

 

Dr. Beth Faiman, a myeloma expert and researcher, discusses factors that should be considered when deciding to undergo CAR T-cell therapy, advice for preparing for and after the process, and why a good support team is essential. Dr. Faiman also shares research updates in CAR T-cell therapy, and alternatives options to this myeloma treatment.

Dr. Beth Faiman is an Adult Nurse Practitioner in the department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. Learn more about Dr. Faiman.

See More From Thrive CAR T-Cell Therapy

Download Resource Guide

Transcript:

Katherine Banwell:

Welcome. I’m your host, Katherine Banwell. As patients navigate their myeloma care, it’s essential for them to feel formed when engaging with their care team. That’s why the Patient Empowerment Network developed the Thrive series, to share support and educational resources so that patients can feel confident at every stage of their care. In today’s program, we’re going to hear from a renowned myeloma expert as we discuss CAR-T therapy. Before we meet today’s guest, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.  

Well, joining us today is Dr. Beth Faiman. Dr. Faiman, welcome. Would you please introduce yourself?  

Dr. Beth Faiman:

Thank you so much, Katherine, and it’s such an honor and a pleasure to be here today. My name is Beth Faiman. I am a nurse practitioner and a PhD researcher at the Cleveland Clinic in Cleveland, Ohio, where I have worked since 1994, in the field of myeloma mostly. Thank you.  

Katherine Banwell:

Excellent. Thank you so much for joining us today. As I mentioned, today’s program is part of our Thrive series. So, from your perspective, what does it mean to thrive with myeloma?  

Dr. Beth Faiman:

So, to thrive with myeloma is something that when I started managing patients in the 1990s individuals didn’t live very long, maybe two to three years, because we did not have good therapies. Now, we talk about living well with myeloma, thriving with myeloma. It just makes me so happy. I think for plants. I think of flowers that can grow in the right environment. I had a plant in my office recently that somebody had gifted me, and it sat there and tried to soak up the little bit of sunlight that it could muster and just wasn’t doing well.  

So, I brought it home and I put it in a big window. That plant is beautiful now and I just love looking at it and thinking about it. And it reminds me of how if you’re in your right environment with multiple myeloma you surround yourself with friends, families, coworkers, church friends, or places of worship, then you can really thrive in that environment or you can grow. And even though you have a cancer diagnosis, that is not – and I hate to use the D-word – a death sentence anymore. You can live many years and live well with myeloma in the right environment like my little plant.  

Katherine Banwell:

That’s a great idea to think about. Thank you. Well, we’ve covered this in recent webinars but it’s worth sharing again. Can you give us an overview of the process and timeline for someone choosing CAR T-cell therapy for myeloma treatment?  

Dr. Beth Faiman:

Yes. So, CAR T-cell therapy, when we first started discussing this in the mid-2000s, I thought this was science fiction.  

Taking somebody’s own cells, engineering them to be fighters against the cancer cells. I thought it was science fiction. But now, we have two FDA approved therapies for multiple myeloma. It’s Ide-cel, which was approved in 2021 and Cilta-cel, approved in 2022.  

Now, the process is lengthy and I know you’ve covered this before but from my perspective, I think if you want to take something home form this webinar, plan early. So, you need to have three prior lines of therapy as a myeloma patient to qualify for this treatment. But you can start planning for it ahead of time.  

So, it’s not available in every center. So, you want to start researching what the closest center would be for you to have this therapy. Many different patient support networks will have these centers on their websites. So anyhow, you find out.  

“Okay. I want to learn more about a CAR T-cell therapy.” Then you have to meet with a specialist. So, you get that education, have that referral, and meet with a specialist at a center that does CAR T-cell therapy. And that might be where you got your initial transplant if you’ve then returned to the community. After that, then we find a slot for you when it’s ready. So, there is that process of financial, physical, social things that are checked in the background. You meet with a social worker, nurses, etc.  

Once you’ve confirmed that you’re going to go through this process – now, it might be three, six, nine months in the future, if you’re a planner – but if you want to just gain information, it’s that harvesting and storing of the cells. That’s where I try to tell people age is not a number. You can be at any age and you qualify for this therapy. We’ve had people well into their late 70s to early 80s who have gotten these therapies.   

Long story short, it’s a process.  

You get your cells harvested and then while they’re being manufactured into fighters, they take the T cells from your blood through an apheresis machine and freeze them, send them off, make them into fighters, and then reinfuse them in your bloodstream. It’s a long process. It can take anywhere from two to three months from when you decide it’s right for you.  

Katherine Banwell:

Well, thank you for explaining that. That’s really important. It puts into perspective. It’s a big undertaking. But also, quite manageable, I think, right, with the right team and support. Who are the members?   

Dr. Beth Faiman:

Absolutely. The family members, friends, and, of course – I like to use the words the multidisciplinary team. That’s your physicians, your social workers, nurses, nurse practitioners like me, pharmacists, and then all your other specialists.  

So really, mounting that team from diagnosis and throughout your whole journey as a myeloma patient can really enrichen your life and help you thrive in that environment.  

Katherine Banwell:

Yeah. It sounds like there’s a lot of support for someone going through this process and that the care partner also plays a critical role on the care team, right?  

Dr. Beth Faiman:

Oh, absolutely. So, I am a big advocate for care partner though not everybody has a caregiver. So, it can be a formal caregiver, somebody’s spouse, daughter, son, significant other. Or it can be an informal caregiver. So, I’ve had patients that – because you need to have a care partner to qualify for CAR T-cell therapy, because patients need to be monitored for about 30 days afterwards. So, that might be pulling in friends from your place of worship, people from the community, and then also people from the cancer center.  

Some of the larger centers that do the CART-cell therapy have a network setup where you get this list of people that have volunteered to drive you to appointments or maybe arrange for Uber help to drive you back and forth. I am not plugging Uber or Lyft, but a rideshare company. And so, finding out those resources can help anyone – just about anyone – access these CAR  T-cell therapies, because you can have a long-term remission. Think about somebody who’s been through treatment A, B, C, or D and then now, “Gosh, maybe my life is going to be shortened.”  

Not necessarily. If this is the right recipe to control their myeloma then they can get 11, 24 months off of everything – just antibiotics – and be monitored. And so, it puts them at a position where if you can get the care partner, get a care team, to support you then you can have access to a potentially life extending with good quality of life therapy.   

Katherine Banwell:

Yeah. I’m sure many of our viewers today are wondering who the therapy is right for and when is it most appropriate in the course of myeloma? Could you address that?  

Dr. Beth Faiman:

Yeah, absolutely. So, currently, you have to have had three prior lines of therapy with drugs such as a CD38, which is – daratumumab (Darzalex) is a name of a medication.  

You have to have a drug such as lenalidomide (Revlimid) as well as a drug like bortezomib (Velcade). And you have to have had three lines of therapy. So, that’s how you can access the therapy. But if you’re willing to participate in a well-designed clinical trial there are studies with CAR T-cell therapy earlier on.  

So, one of the things that we’re advocating in the myeloma world is clinical trials. We haven’t gotten to where we are in 2024 with the advances in sciences, the advances in living longer and living well with myeloma, without the brave people before us that have participated in clinical trials. 

So, people who it’s right for would be if they qualify for a clinical trial before their third or fourth line of therapy or if they’ve had three or four prior lines of therapy. And there are other points to that which I’m sure we’ll talk about later on.  

Katherine Banwell:

In your opinion, what are three key considerations that myeloma patients and care partners should think about related to the CAR T-cell therapy approach?   

Dr. Beth Faiman:

Oh, gosh. Well, I would like to say that always when you’re selecting a therapy, think of the physical, the financial, and the social implications of that therapy. So, physically is the medication too strong for you? Are you too weak to take it? Or is it just right for you? So, finding the right medication for the right patient at the right dose at the right time. So, the physical component. The financial component is also very important. So, maybe your insurance now won’t cover it but then there’s open enrollment in Medicare towards the end of the year or you can find financial support reimbursement through many of our generous organizations that will provide grants for certain medications.  

And then, the social. Do you have a care partner, as we discussed? The importance of being monitored for 30 days. If you don’t have a formal care partner, is there some system that we can help support you through so that you can have the different supports throughout. It’s not only that beginning part where you’re gaining the information – and I think of it like a timeline. The beginning part, you’re thinking about gathering information to the – in that process of getting yourselves back because of the side effects, which I think have been talked about in a prior webinar.  

And then, the post-monitoring where you go back to your community, taking antibiotics, antiviral medications, etc., to keep you living well longer. So, it’s a process.  

Katherine Banwell:

Well, it’s great advice, Dr. Faiman, thank you. I’d also like to add that if you’re considering CAR T-cell therapy, the Patient Empowerment Network has a wealth of information on this topic, including resource guides and interviews with experts like Dr. Faiman. 

And you can find those at powerfulpatients.org/myeloma. So, Dr. Faiman, when a patient is talking with their care team about CAR T-cell therapy, what questions should they be asking to help determine if CAR-T is even right for them?  

Dr. Beth Faiman:

Katherine, that’s an excellent question. So, let’s just say that somebody from Patient Empowerment Network heard about CAR T-cell therapy for myeloma and then sought out a local institution that might be conducting that procedure. So then, they come for that visit and what you mentioned was just spot on, getting a list of questions together. What we do at my institution, as well as many throughout the country, is a process called shared decision-making.  

You might’ve talked about this on prior webinars, but shared decision-making occurs when that healthcare team, such as the physician, nurse practitioner, pharmacist, whoever, shares information with the patient and their care partner.  

You mutually share information to arrive at a decision. So, many studies have been done on shared decision-making. It’s done in many different areas. And so, through that sharing of information, you might think of different questions.  

Some of the things that I try to proactively offer – we all have our list of things that we educate our patients on, but some of the things I proactively will recommend to patients and their care partners when you’re seeking an opinion at these centers is, “How long will I be sick? What are the biggest side effects of the medication I have to worry about?” Asking your care team – I know it sounds silly, but are they aware of all your prior health concerns, especially if you’re coming for an evaluation.  

Maybe you have peripheral neuropathy where you have numbness and tingling in your fingers or toes or a history of kidney disease. Your kidneys look fine now but maybe a few years ago at the myeloma diagnosis the kidneys had a temporary failing and now they’re better so they’d want to protect you with future medications. How long will you have to take medications after the CAR-T procedure? There’s antiviral medicines, antibacterial medications, and medications called IVIG, which strengthens your immune system.  

And then, finally, asking about the infection protection afterwards. Do you have to get vaccinated again against pneumococcal, shingles, and all of those other things that we do. The cellular therapy guidelines suggest timepoint for one, three, five, etc., months after CAR T-cell procedure to get revaccinated. So, who’s going to do that for you?  

How are you going to know what to get? So, make sure that they give you a timeline, calendars, and set expectations for what you need to do as a patient and then you’ll help them set expectations for what they need to do to provide you the accurate education.  

Katherine Banwell:

Well, talking about what to expect after CAR T-cell therapy, would you tell us what some of the potential side effects are?  

Dr. Beth Faiman:

Oh, absolutely. So, CAR T-cell therapy – again, it harnesses your immune system using your T cells. Your T cells are so important in your immune system to be programmed as fighters. And as people age, or as long as – after they’ve had myeloma or other kinds of cancers, those T cells just don’t work as well. So, what we want to do is engineer them and program them with what we call a viral vector to be fighters. So, those T cells, as I mentioned, are harvested, stored, and then manufactured to go. 

And I tell people it’s like that Pac-Man video game. It goes around in your bloodstream just kind of eating away at the myeloma cells. So, you don’t take any medications. You don’t go in for IVs every week or twice weekly, or taking pills at home to treat the myeloma. It’s what we consider a one-and-done thing. So, if it works for you, it can keep you in remission for quite some time. But if it doesn’t work then there still are other therapies down the road.  

So, the CAR T-cell therapy is something that is an option but there are other therapies out there in many cases. There’s something called a bispecific antibody. There are three currently approved for multiple myeloma now. So, maybe a CAR T-cell therapy doesn’t seem right for you because you’re not in a good remission or the cancer’s too active right now so you don’t have the time to wait for manufacturing of the cells and putting them back in your bloodstream.  

Those bispecifics will fill that gap. So, when you’re discussing the options, aside from clinical trials and other drugs, the bispecific antibody is very similar. One of the things that I wanted to highlight is that nowadays we’re into these things called sequencing. So, we’re trying to figure out what order to give these super effective drugs. Should we give the bispecific antibodies first or should we give the CAR T-cell therapy first? And in most centers, if you have time to wait and you’re planning, the CAR T-cell therapy is right for most people and then the bispecifics would come later.  

Katherine Banwell:

All right. So, after CAR T-cell therapy is completed, what potential side effects might people experience, and what should they look for?  

Dr. Beth Faiman:

Absolutely. I think of things in short-term and long-term side effects. So, the short term, you’re going to be admitted to the hospital and you have a risk for – when we get those T cells back – that cytokine release syndrome, or it’s abbreviated CRS – where you’re body’s immune system’s fighting.  

I tell folks it’s kind of like if you got a vaccine for a flu vaccine or pneumonia and you had a reaction it’s just way worse. So, you can get a high fever – the big first sign of this CRS. Usually, the providers will jump in with giving you a medication called tocilizumab (Actemra) or a similar drug that blocks IL-6, which is a chemical that is triggered when we get the CRS. And then, it stops those symptoms. And so, most of us know how to do that and will approve your insurance to get access to that tocilizumab or similar drug when we approve your CAR T-cell therapy.  

So, that CRS can get you really, really sick. You can get low oxygen levels in your blood. You can get a high fever and you can drop your blood pressure. But most CAR T-cells centers, the nurses and the staff are very well-trained to monitor this every eight hours, in most cases.  

Another rare side effect we worry about is ICANS and it’s a neurotoxicity kind of thing.  

It can be with CRS or without CRS. But they’ll ask you to do things like write your name on a piece of paper every eight hours or tell me – draw a clock or count backwards from 100. And so, if you have any deviation, even minor, from what you reported back beforehand then we worry about neurotoxicity. Now, that’s short term but that’s the reason why you can’t drive a car for 30 days is because it could be delayed. 

The CRS can start with the one thing, the ide-cel usually occurs within one day so most people are admitted to the hospital for that CAR T-cell therapy. The Cilta-cel, it onsets to about seven days. So, some people get the cilta-cel outpatient and then are monitored daily, whether in person or through virtual telehealth monitoring.  

But at any rate, those are the short-term. Long-term, we worry about low blood counts maybe for the first month afterwards. And then, those will come back to normal. And then, we worry about infection. So, I mentioned the antibacterial, antiviral, which is usually a medicine called acyclovir (Zovirax), which most myeloma patients will have been on anyhow. And then, that IVIG to protect against viruses and bacteria when your immune system is so low. 

But fortunately, if we control the CRS, it usually comes with the CRS, although it can be independent. We try not to give steroids, because we don’t want it to interrupt the CAR T-cell process. But many institutions will give that tocilizumab for ICANS. And if that doesn’t get better then they’ll give you a steroid, such as dexamethasone (Decadron). 

And so, that will usually reverse itself pretty quickly. Longer term, after 30 days, you can get with the Carvykti, particularly something called Parkinsonian things where you can get a little bit shaky or something like that. Again, it’s very rare and I have had hundreds of people who have undergone the CAR T-cell procedure at my institution. And knock on wood, fortunately, I’ve not seen first-hand that side effect. And I think it’s because we’re so good now at treating the – preventing the ICANS and CRS as best as we can while they’re inpatient and doing real close following.  

One other thing I want to note is if somebody who’s watching this does go in the hospital for any reason, get up and walk around and stay strong, as well as you can, during the procedure. You might be bored if you’re in the hospital anyhow, but try to stay as strong as you can in the hospital. It’ll help your post recovery for sure.  

Katherine Banwell:

Well, what about more mild side effects like fatigue and changes in appetite?   

Dr. Beth Faiman:

Absolutely. So, the fatigue and the changes in appetite are generally mild for most but I see it, in my experience, if your myeloma’s acting up really quickly, if you’re having a rapid disease progression, the medications that we give you to control the myeloma during this bridging therapy phase might cause some of that as well, not necessarily the CAR T-cell process. But think about it. We’re using your own cells engineered to be fighters.  

And so, that first month or two is probably when you’re going to be the most tired as your body is being programmed to fight against the myeloma cells. That fatigue tends to get better. And as I mentioned just a moment earlier, the importance of just walking around in the halls, getting out of bed when you’re in the hospital, that can really help your post recovery. It doesn’t seem like much, but there have been many studies about how muscle mass declines, energy declines when you’re hospitalized.  

And we want you to be as strong as you can and thrive as much as you can for when you’re out you can then do the things you want to do at a quicker pace.   

Katherine Banwell:

Right. That’s great advice. Beyond monitoring of any issues, what can someone expect related to returning to life as they knew it before the diagnosis? Is there a timeline for resuming lifestyle and activity?  

Dr. Beth Faiman:

Yeah. So, I should say I because it’s from my perspective. I am a real strong advocate. I tell people to do what you feel like you can physically do. We know that myeloma can affect the bones and put your bones at risk for breaking and so we give you medicines to protect it. So, I do put some restrictions however on physical activity in terms of, “I don’t want you to bench press 40 pounds or 20 pounds,” in most cases. And depending on what the bones look like on x-ray, I’ll even restrict it to about five to 10 pounds.  

If you think about it, that’s a bag of potatoes. So, you don’t want to put too many restrictions on for everybody. But talk to your healthcare provider about what your specific restrictions are with physical activity. Because I don’t really put any restrictions on but I encourage things like riding a bike, especially a stationary bike in your own home, so that if you fall off – hopefully, you won’t fall off a stationary bike. But if you injure yourself, then you’re able to be in a place that somebody can help you.  

But riding a bike. Also, exercising in water. Water therapy is a great weight bearing exercise and there are times of day where you can go when the YMCAs or YWCAs aren’t as busy – or community centers. So, you’re less at risk for bacterial or other illnesses. But during that first month, I try to limit their exposure to people because you’re at risk for the different viruses that are all over the place, the bacterial infections. 

So, that first month is the critical period where I try to say, “Okay, try to lay low. Let’s get you through this period. Your immune system will start getting stronger on its own after this period.” And then, that month two you start feeling like doing more. You go to the grocery store. You maybe go to eat out at a restaurant but pick a time of day that’s less busy. So, go for an early dinner. There’s no shame in eating at 5:00 p.m. if you want to go out. And then, get a table in the corner with your own wipes. And so, that’s where your immune system is getting stronger. 

And then, by month three, I think most people will feel much, much better and much, much stronger. And if you can keep moving throughout this whole time, then you’ll be stronger on the way out.  

Katherine Banwell:

Dr. Faiman, from what you’ve described, undergoing CAR T-cell therapy can be a very intense process. Why would someone consider this option over another myeloma treatment option?  

Dr. Beth Faiman:

Yeah. So, the CAR T-cell therapies have really transformed myeloma, in my opinion.  

When we first started using CAR T-cell therapies, there was a long wait list because people who had had three, five, seven, 10, 12 prior therapies, they had very few other options. So, we had ethically assigned scores to people as to who – we’d get one or two slots a month and then we’d have 80-some people on this list. And we’re thinking, “How do we allocate who’s going to get this therapy?” And it’s because you can have a nice, long remission off of all therapy.  

It’s a great, great option for most people. Again, I would hope that we can get this moved further into the disease trajectory. There are actually two studies. One was a KarMMa study. It was published in the New England Journal of Medicine in 2023, early part of 2023.  

And it showed that when people get this therapy earlier, the Ide-cel first, you can have a longer remission. So, we’re talking about three, four, five or more prior lines of therapy you can get about 11 months with the Ide-cel.  

You could even get a longer remission off of all therapy if you move it earlier. Same with Cilta-cel. We had studies and different cohorts and you can be in a long remission. So, think of somebody who’s – myeloma’s incurable. It’s very treatable but it’s incurable for most. And so, you go from the expectation of staying on treatment until disease progression, much like other chronic conditions like diabetes. We don’t stop medicine for diabetes or high blood pressure.  

And it’s the same with myeloma and many of the cancers that we treat these days. And so, a CAR T-cell therapy will give patients the option of having that disease free interval where you can go and travel the world. I have patients that have bought RVs after their CAR T-cell therapy and now they’re going around the world – well, not the world. But around the United States.  

Katherine Banwell:

The country. 

Dr. Beth Faiman:

The country. And just really enjoying life and taking that time off and being realistic, knowing that we have to do bloodwork every month to make sure the myeloma’s still in remission because it can come back. But at least it’s sleeping for right now. So, you can go out and enjoy your life and take those trips and enjoy the little things and the big things.  

Katherine Banwell:

Yeah. Well, thank you for that advice. I’d like to get to a few audience questions that were sent in prior to the program. Alice asks, can you share more information about T-cell collection? A recent webinar mentioned that myeloma must be in good control. Can you share specifics about the bridging therapy prior to infusion?  

Dr. Beth Faiman:

Yes. So, again, the process is the lengthy process as we mentioned before. But for the actual T-cell collection, we will have approved you to get the therapy. Financially, we’ve cleared you. Socially, you’ve gotten your support systems and now we’re getting those cells out.  

We use a process called apheresis where a temporary catheter is placed under the skin, and it separates your white blood cells and then returns the red bloods and plasma back into the blood. And it sorts out those T cells. The process itself, you’re on the machine for anywhere for two or three hours. Hopefully, it’ll just be one day’s time. And then, they’ll manufacture those cells.  

So, during that period where we’ve put your cells and sent them away to wherever’s going to be doing the manufacturing, you’re going to need to get a treatment that’s going to keep you in remission from the myeloma. And it’s not going to prevent you from getting those cells safely back. So, we don’t want anything that’s too toxic for most people. So, what we’re doing now is we have that information that early on is better for myeloma to get these treatments. And so, the hope that bridging therapy won’t be as common of a thing anymore.  

Because now we’re selecting people that are – the myeloma’s just starting to act up. Let’s get those cells out, send them off, so we don’t have to do bridging therapy. We can just keep you – add a medication or take away another medication to keep you in remission. So, that’s the goal of bridging therapy. What’s that bridge to get your cells back in for some people? It might be a chemotherapy type of a thing. But for other people it’s just trying to get you that CAR T-cell collection and manufacturing so we don’t really have to change everything all up.  

And we’ve been very fortunate now that the wait lists have cleared in most institutions. CAR-T cell is available at more centers across the country and so we don’t have that backlog. And so, fortunately, bridging therapy will hopefully be a little bit less of a thing.  

Katherine Banwell:

We have another question. This one from Rita. What kind of monitoring takes places in the months following CAR T-cell therapy and what kinds of medicines are required afterward?  

Dr. Beth Faiman:

Oh, excellent. So, the monitoring is usually on the short-term, within the first 30 to 60 days afterwards, oftentimes depending on what your blood counts are showing. You might have to get blood counts tested more frequently. So, that complete blood count shows you the white cells, the red cells. The white cells fight infection. Red cells carry oxygen. Platelets clot the blood. That’s a marker of how well your bone marrow is functioning. It also can be – those innocent bystanders can go low temporarily after this procedure.  

So, definitely those CBCs need to be tested, for some people weekly and for some people every other week. And your healthcare team will tell you how often. After that first two to three months and your blood counts are all in good shape, then we can just go oftentimes to a monthly monitoring of the myeloma labs. So, that’s the CBC and the chemistry panel but also the paraproteins in the blood and the urine get monitored.  

There’s also another test called a CD4 count that’s something that you wouldn’t have had beforehand. The CD4 count is an immune count that we want to be over 200. Oftentimes,  you’ll be on an antibiotic called Bactrim or an inhaled called pentamidine to lessen the chance of a certain kind of infection called PJP, or pneumocystis. So, those are those atypical infections that we’re now seeing with CAR-T cell and other therapies.  

And as I mentioned, acyclovir to protect against shingles is a medication but you’re not going to be on any anti-myeloma medications other than maybe a bone strengthener if you get that intermittently. Fortunately, after CAR-T cell, you don’t have any anti myeloma therapy as long as you’re in remission.  

Katherine Banwell:

We also received this question from a viewer named Rob. If you receive CAR-T therapy, how long does it last and have you seen remission for a long time?  

Dr. Beth Faiman:

So, I’d like to tell Rob that I’ve seen a little bit of a remission and I’ve seen long-time remissions. Unfortunately, it goes back to the biology of the disease. People that have a more aggressive type of myeloma tend to not have as long of a remission but that’s not always the case. So, if you have what’s called a standard type of myeloma, which fortunately about 80 percent of the people have a standard or good type of myeloma, you can get an 11- to 24-month remission if you’ve had many prior therapies.  

Now, if we’re moving the CAR-T earlier lines of therapy, as in those two studies that I briefly mentioned with the Ide-cel and the Cilta-cel studies that are moving it to one to three prior lines of therapy, people are getting longer remissions.  

Unfortunately, I do not have a crystal ball. I can look at your disease genetics. I can look at how deep your remission status is and I can generally predict based on other studies how long of a remission you might get, but it’s not a guarantee. What works for one person might not work for the other so you take it with a grain of salt. We just say, “Gosh, this is a great therapy. We need to offer it to you while we have that window of opportunity. You’re in a good remission. We have a slot for you. We’re going to pick the best product for you. Let’s give you this option.” 

You might be one of those exceptional responders that are in remission for several years, which I do have people that have been in remission several years, fortunately.  

Katherine Banwell:

Okay. Well, thank you so much for the thoughtful responses to those questions. As we close out today’s program, can you talk about some of the ongoing research in CAR T-cell therapy and what you’re excited about?  

Dr. Beth Faiman:

Oh, my gosh. I am so excited about CAR T-cell therapy research. There are these what we call CRISPR gene edited technology, which is really personalizing the treatment in CAR-T.  

There’s what we call an off-the-shelf approach where we don’t have to manufacture one’s T cells to be a fighter. So, these CAR T-cell therapies are the kinds of clinical studies where if you are in a position where you want to hopefully get an earlier access to a great therapy, this CRISPR edited at – Caribou is what it’s called, that we have at my institution. That might be right for you.  

There’s also the different targets. For example, the Ide-cel and the Cilta-cel target what’s called BCMA or B-cell maturation antigen. Basically, the BCMA is expressed mostly on cancer cells and less so on healthy cells.  

And so, that’s what the target is for these current CAR-Ts. We have different targets. So, what does that mean for you? If you had a CAR T-cell therapy against BCMA or a bispecific against BCMA now we have these different targets so that gives you other options for remissions status. So, if you can, I am a big, strong advocate for clinical trials. Like I said, it’s getting better access. You have a healthcare team. There’s so much stigma associated with clinical trials, but every single person is a candidate for some sort of a trial or another.  

So, talk to your healthcare team or you can go to clinicaltrials.gov and then all the patient care organizations – International Myeloma Foundation, Multiple Myeloma Research Foundation, has access to clinical trial information as well for patients. So, yes, lots of good things. New targets. Off-the-shelf so you don’t have to manufacture. So, that represents new treatment options for many patients.  

Katherine Banwell:

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

Dr. Beth Faiman:

My pleasure. Thank you for having me.  

Katherine Banwell:

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

CAR T-Cell Therapy | Key Considerations for Myeloma Patients

CAR T-Cell Therapy | Key Considerations for Myeloma Patients from Patient Empowerment Network on Vimeo.

Myeloma expert and researcher Dr. Beth Faiman shares key considerations when planning for CAR T-cell therapy. Dr. Faiman reviews which patients qualify for CAR T-cell therapy, key aspects for patients to consider, and resources for clinical trials and CAR T-cell therapy information.

Dr. Beth Faiman is an Adult Nurse Practitioner in the department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. Learn more about Dr. Faiman.

See More From Thrive CAR T-Cell Therapy

Download Resource Guide

Related Resources:

Planning for CAR T-Cell Therapy | Advice for Myeloma Patients

Planning for CAR T-Cell Therapy | Advice for Myeloma Patients

Considering CAR T-Cell Therapy | Key Advice From an Expert

Considering CAR T-Cell Therapy? Key Advice From an Expert 

What Side Effects Are Possible Following CAR T-Cell Therapy?

What Side Effects Are Possible Following CAR T-Cell Therapy?

Transcript:

Katherine Banwell:

I’m sure many of our viewers today are wondering who the therapy is right for, and when is it most appropriate in the course of myeloma? Could you address that?  

Dr. Beth Faiman:

Yeah, absolutely. So, currently, you have to have had three prior lines of therapy with drugs such as a CD38, which is – daratumumab (Darzalex) is a name of a medication.   

You have to have a drug such as lenalidomide (Revlimid) as well as a drug like bortezomib (Velcade). And you have to have had three lines of therapy. So, that’s how you can access the therapy. But if you’re willing to participate in a well-designed clinical trial there are studies with CAR T-cell therapy earlier on.  

So, one of the things that we’re advocating in the myeloma world is clinical trials. We haven’t gotten to where we are in 2024 with the advances in sciences, the advances in living longer and living well with myeloma, without the brave people before us that have participated in clinical trials.   

So, people who it’s right for would be if they qualify for a clinical trial before their third or fourth line of therapy or if they’ve had three or four prior lines of therapy.   

And there are other points to that which I’m sure we’ll talk about later on.  

Katherine Banwell:

In your opinion, what are three key considerations that myeloma patients and care partners should think about related to the CAR T-cell therapy approach?  

Dr. Beth Faiman:

Well, I would like to say that always when you’re selecting a therapy, think of the physical, the financial, and the social implications of that therapy. So, physically is the medication too strong for you? Are you too weak to take it? Or is it just right for you? So, finding the right medication for the right patient at the right dose at the right time. So, the physical component.

The financial component is also very important. So, maybe your insurance now won’t cover it but then there’s open enrollment in Medicare towards the end of the year or you can find financial support reimbursement through many of our generous organizations that will provide grants for certain medications.  

And then, the social. Do you have a care partner, as we discussed? The importance of being monitored for 30 days. If you don’t have a formal care partner, is there some system that we can help support you through so that you can have the different supports throughout. It’s not only that beginning part where you’re gaining the information – and I think of it like a timeline. The beginning part, you’re thinking about gathering information to the – in that process of getting yourselves back because of the side effects, which I think have been talked about in a prior webinar.  

And then, the post-monitoring where you go back to your community, taking antibiotics, antiviral medications, etc., to keep you living well longer. So, it’s a process.   

Katherine Banwell:

Well, it’s great advice, Dr. Faiman, thank you. I’d also like to add that if you’re considering CAR T-cell therapy, the Patient Empowerment Network has a wealth of information on this topic, including resource guides and interviews with experts like Dr. Faiman. And you can find those at powerfulpatients.org/myeloma.  

Planning for CAR T-Cell Therapy | Advice for Myeloma Patients

Planning for CAR T-Cell Therapy | Advice for Myeloma Patients from Patient Empowerment Network on Vimeo.

How can myeloma patients plan and prepare for CAR T-cell therapy? Myeloma expert and researcher Dr. Beth Faiman shares an overview of eligibility requirements, appointments to coordinate, multidisciplinary team members, and support resources to help in planning.

Dr. Beth Faiman is an Adult Nurse Practitioner in the department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. Learn more about Dr. Faiman.

See More From Thrive CAR T-Cell Therapy

Download Resource Guide

Related Resources:

Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

Considering CAR T-Cell Therapy | Key Advice From an Expert

Considering CAR T-Cell Therapy? Key Advice From an Expert 

What Do You Need to Know When Considering CAR T-Cell Therapy?

What Do You Need to Know When Considering CAR T-Cell Therapy?

Transcript:

Katherine Banwell:

Can you give us an overview of the process and timeline for someone choosing CAR T-cell therapy for myeloma treatment?   

Dr. Beth Faiman:

Yes. So, CAR T-cell therapy, when we first started discussing this in the mid-2000s, I thought this was science fiction.  

Taking somebody’s own cells, engineering them to be fighters against the cancer cells. I thought it was science fiction. But now, we have two FDA-approved therapies for multiple myeloma. It’s Ide-cel, which was approved in 2021 and Cilta-cel, approved in 2022.  

Now, the process is lengthy, and I know you’ve covered this before but from my perspective, I think if you want to take something home form this webinar, plan early. So, you need to have three prior lines of therapy as a myeloma patient to qualify for this treatment. But you can start planning for it ahead of time.  

So, it’s not available in every center. So, you want to start researching what the closest center would be for you to have this therapy. Many different patient support networks will have these centers on their websites. So anyhow, you find out.  

“Okay. I want to learn more about a CAR T-cell therapy.” Then you have to meet with a specialist. So, you get that education, have that referral, and meet with a specialist at a center that does CAR T-cell therapy. And that might be where you got your initial transplant if you’ve then returned to the community. After that, then we find a slot for you when it’s ready. So, there is that process of financial, physical, social things that are checked in the background. You meet with a social worker, nurses, etc.  

Once you’ve confirmed that you’re going to go through this process – now, it might be three, six, nine months in the future, if you’re a planner – but if you want to just gain information, it’s that harvesting and storing of the cells. That’s where I try to tell people age is not a number. You can be at any age and you qualify for this therapy. We’ve had people well into their late 70s to early 80s who have gotten these therapies. Long story short, it’s a process.  

You get your cells harvested and then while they’re being manufactured into fighters, they take the T cells from your blood through an apheresis machine and freeze them, send them off, make them into fighters, and then reinfuse them in your bloodstream. It’s a long process. It can take anywhere from two to three months from when you decide it’s right for you.  

Katherine Banwell:

Well, thank you for explaining that. That’s really important. It puts into perspective. It’s a big undertaking. But also, quite manageable, I think, right, with the right team and support. Who are the members?  

Dr. Beth Faiman:

Absolutely. The family members, friends, and, of course – I like to use the words the multidisciplinary team. That’s your physicians, your social workers, nurses, nurse practitioners like me, pharmacists, and then all your other specialists.  

So really, mounting that team from diagnosis and throughout your whole journey as a myeloma patient can really enrichen your life and help you thrive in that environment.  

Katherine Banwell:

Yeah. It sounds like there’s a lot of support for someone going through this process and that the care partner also plays a critical role on the care team, right?  

Dr. Beth Faiman:

Oh, absolutely. So, I am a big advocate for care partner though not everybody has a caregiver. So, it can be a formal caregiver, somebody’s spouse, daughter, son, significant other. Or it can be an informal caregiver. So, I’ve had patients that – because you need to have a care partner to qualify for CAR T-cell therapy, because patients need to be monitored for about 30 days afterwards. So, that might be pulling in friends from your place of worship, people from the community, and then also people from the cancer center.  

Some of the larger centers that do the CART-cell therapy have a network setup where you get this list of people that have volunteered to drive you to appointments or maybe arrange for Uber help to drive you back and forth. I am not plugging Uber or Lyft, but a rideshare company.

And so, finding out those resources can help anyone – just about anyone – access these CAR  T-cell therapies, because you can have a long-term remission. Think about somebody who’s been through treatment A, B, C, or D and then now, “Gosh, maybe my life is going to be shortened.”  

Not necessarily. If this is the right recipe to control their myeloma then they can get 11, 24 months off of everything – just antibiotics – and be monitored. And so, it puts them at a position where if you can get the care partner, get a care team, to support you then you can have access to a potentially life extending with good quality of life therapy.   

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale from Patient Empowerment Network on Vimeo.

What concerns do myeloma patients need to know about CAR T-cell therapy? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains patient qualification for CAR T-cell therapy, including the number and type of prior therapies.

Download Guide  |  Descargar Guía

See More from START HERE Myeloma

Related Programs:

What Factors Shape Myeloma Treatment Options After Relapse?

Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps

How is Treatment Fitness Determined in Multiple Myeloma?


Transcript:

Lisa Hatfield:

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:

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 (Revlimid), 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 Ts 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 an 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.


Share Your Feedback:

Create your own user feedback survey

Thrive | Considering CAR T-Cell Therapy for Myeloma? What You Should Know

Thrive | Considering CAR T-Cell Therapy for Myeloma? What You Should Know from Patient Empowerment Network on Vimeo.

 Dr. Beth Faiman, a myeloma expert and researcher, discusses factors that should be considered when deciding to undergo CAR T-cell therapy, advice for preparing for and after the process, and why a good support team is essential. Dr. Faiman also shares research updates in CAR T-cell therapy, and alternatives options to this myeloma treatment.

Dr. Beth Faiman is an Adult Nurse Practitioner in the department of Hematologic Oncology and Blood Disorders at the Cleveland Clinic. Learn more about Dr. Faiman.

See More From Thrive CAR T-Cell Therapy

Download Resource Guide

Related Resources:

What Do You Need to Know When Considering CAR T-Cell Therapy?

What Do You Need to Know When Considering CAR T-Cell Therapy?

Considering CAR T-Cell Therapy | Key Advice From an Expert

Considering CAR T-Cell Therapy? Key Advice From an Expert 

Thrive | Advice for Managing Potential CAR T-Cell Therapy Side Effects 

Transcript:

Katherine Banwell:

Welcome. I’m your host, Katherine Banwell. As patients navigate their myeloma care, it’s essential for them to feel formed when engaging with their care team. That’s why the Patient Empowerment Network developed the Thrive series, to share support and educational resources so that patients can feel confident at every stage of their care. In today’s program, we’re going to hear from a renowned myeloma expert as we discuss CAR-T therapy. Before we meet today’s guest, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.  

Well, joining us today is Dr. Beth Faiman. Dr. Faiman, welcome. Would you please introduce yourself?  

Dr. Beth Faiman:

Thank you so much, Katherine, and it’s such an honor and a pleasure to be here today. My name is Beth Faiman. I am a nurse practitioner and a PhD researcher at the Cleveland Clinic in Cleveland, Ohio, where I have worked since 1994, in the field of myeloma mostly. Thank you.  

Katherine Banwell:

Excellent. Thank you so much for joining us today. As I mentioned, today’s program is part of our Thrive series. So, from your perspective, what does it mean to thrive with myeloma?  

Dr. Beth Faiman:

So, to thrive with myeloma is something that when I started managing patients in the 1990s individuals didn’t live very long, maybe two to three years, because we did not have good therapies. Now, we talk about living well with myeloma, thriving with myeloma. It just makes me so happy. I think for plants. I think of flowers that can grow in the right environment. I had a plant in my office recently that somebody had gifted me, and it sat there and tried to soak up the little bit of sunlight that it could muster and just wasn’t doing well.  

So, I brought it home and I put it in a big window. That plant is beautiful now and I just love looking at it and thinking about it. And it reminds me of how if you’re in your right environment with multiple myeloma you surround yourself with friends, families, coworkers, church friends, or places of worship, then you can really thrive in that environment or you can grow. And even though you have a cancer diagnosis, that is not – and I hate to use the D-word – a death sentence anymore. You can live many years and live well with myeloma in the right environment like my little plant.  

Katherine Banwell:

That’s a great idea to think about. Thank you. Well, we’ve covered this in recent webinars but it’s worth sharing again. Can you give us an overview of the process and timeline for someone choosing CAR T-cell therapy for myeloma treatment?  

Dr. Beth Faiman:

Yes. So, CAR T-cell therapy, when we first started discussing this in the mid-2000s, I thought this was science fiction.  

Taking somebody’s own cells, engineering them to be fighters against the cancer cells. I thought it was science fiction. But now, we have two FDA approved therapies for multiple myeloma. It’s Ide-cel, which was approved in 2021 and Cilta-cel, approved in 2022.  

Now, the process is lengthy and I know you’ve covered this before but from my perspective, I think if you want to take something home form this webinar, plan early. So, you need to have three prior lines of therapy as a myeloma patient to qualify for this treatment. But you can start planning for it ahead of time.  

So, it’s not available in every center. So, you want to start researching what the closest center would be for you to have this therapy. Many different patient support networks will have these centers on their websites. So anyhow, you find out.  

“Okay. I want to learn more about a CAR T-cell therapy.” Then you have to meet with a specialist. So, you get that education, have that referral, and meet with a specialist at a center that does CAR T-cell therapy. And that might be where you got your initial transplant if you’ve then returned to the community. After that, then we find a slot for you when it’s ready. So, there is that process of financial, physical, social things that are checked in the background. You meet with a social worker, nurses, etc.  

Once you’ve confirmed that you’re going to go through this process – now, it might be three, six, nine months in the future, if you’re a planner – but if you want to just gain information, it’s that harvesting and storing of the cells. That’s where I try to tell people age is not a number. You can be at any age and you qualify for this therapy. We’ve had people well into their late 70s to early 80s who have gotten these therapies.   

Long story short, it’s a process.  

You get your cells harvested and then while they’re being manufactured into fighters, they take the T cells from your blood through an apheresis machine and freeze them, send them off, make them into fighters, and then reinfuse them in your bloodstream. It’s a long process. It can take anywhere from two to three months from when you decide it’s right for you.  

Katherine Banwell:

Well, thank you for explaining that. That’s really important. It puts into perspective. It’s a big undertaking. But also, quite manageable, I think, right, with the right team and support. Who are the members?   

Dr. Beth Faiman:

Absolutely. The family members, friends, and, of course – I like to use the words the multidisciplinary team. That’s your physicians, your social workers, nurses, nurse practitioners like me, pharmacists, and then all your other specialists.  

So really, mounting that team from diagnosis and throughout your whole journey as a myeloma patient can really enrichen your life and help you thrive in that environment.  

Katherine Banwell:

Yeah. It sounds like there’s a lot of support for someone going through this process and that the care partner also plays a critical role on the care team, right?  

Dr. Beth Faiman:

Oh, absolutely. So, I am a big advocate for care partner though not everybody has a caregiver. So, it can be a formal caregiver, somebody’s spouse, daughter, son, significant other. Or it can be an informal caregiver. So, I’ve had patients that – because you need to have a care partner to qualify for CAR T-cell therapy, because patients need to be monitored for about 30 days afterwards. So, that might be pulling in friends from your place of worship, people from the community, and then also people from the cancer center.  

Some of the larger centers that do the CART-cell therapy have a network setup where you get this list of people that have volunteered to drive you to appointments or maybe arrange for Uber help to drive you back and forth. I am not plugging Uber or Lyft, but a rideshare company. And so, finding out those resources can help anyone – just about anyone – access these CAR  T-cell therapies, because you can have a long-term remission. Think about somebody who’s been through treatment A, B, C, or D and then now, “Gosh, maybe my life is going to be shortened.”  

Not necessarily. If this is the right recipe to control their myeloma then they can get 11, 24 months off of everything – just antibiotics – and be monitored. And so, it puts them at a position where if you can get the care partner, get a care team, to support you then you can have access to a potentially life extending with good quality of life therapy.   

Katherine Banwell:

Yeah. I’m sure many of our viewers today are wondering who the therapy is right for and when is it most appropriate in the course of myeloma? Could you address that?  

Dr. Beth Faiman:

Yeah, absolutely. So, currently, you have to have had three prior lines of therapy with drugs such as a CD38, which is – daratumumab (Darzalex) is a name of a medication.  

You have to have a drug such as lenalidomide (Revlimid) as well as a drug like bortezomib (Velcade). And you have to have had three lines of therapy. So, that’s how you can access the therapy. But if you’re willing to participate in a well-designed clinical trial there are studies with CAR T-cell therapy earlier on.  

So, one of the things that we’re advocating in the myeloma world is clinical trials. We haven’t gotten to where we are in 2024 with the advances in sciences, the advances in living longer and living well with myeloma, without the brave people before us that have participated in clinical trials. 

So, people who it’s right for would be if they qualify for a clinical trial before their third or fourth line of therapy or if they’ve had three or four prior lines of therapy. And there are other points to that which I’m sure we’ll talk about later on.  

Katherine Banwell:

In your opinion, what are three key considerations that myeloma patients and care partners should think about related to the CAR T-cell therapy approach?   

Dr. Beth Faiman:

Oh, gosh. Well, I would like to say that always when you’re selecting a therapy, think of the physical, the financial, and the social implications of that therapy. So, physically is the medication too strong for you? Are you too weak to take it? Or is it just right for you? So, finding the right medication for the right patient at the right dose at the right time. So, the physical component. The financial component is also very important. So, maybe your insurance now won’t cover it but then there’s open enrollment in Medicare towards the end of the year or you can find financial support reimbursement through many of our generous organizations that will provide grants for certain medications.  

And then, the social. Do you have a care partner, as we discussed? The importance of being monitored for 30 days. If you don’t have a formal care partner, is there some system that we can help support you through so that you can have the different supports throughout. It’s not only that beginning part where you’re gaining the information – and I think of it like a timeline. The beginning part, you’re thinking about gathering information to the – in that process of getting yourselves back because of the side effects, which I think have been talked about in a prior webinar.  

And then, the post-monitoring where you go back to your community, taking antibiotics, antiviral medications, etc., to keep you living well longer. So, it’s a process.  

Katherine Banwell:

Well, it’s great advice, Dr. Faiman, thank you. I’d also like to add that if you’re considering CAR T-cell therapy, the Patient Empowerment Network has a wealth of information on this topic, including resource guides and interviews with experts like Dr. Faiman. 

And you can find those at powerfulpatients.org/myeloma. So, Dr. Faiman, when a patient is talking with their care team about CAR T-cell therapy, what questions should they be asking to help determine if CAR-T is even right for them?  

Dr. Beth Faiman:

Katherine, that’s an excellent question. So, let’s just say that somebody from Patient Empowerment Network heard about CAR T-cell therapy for myeloma and then sought out a local institution that might be conducting that procedure. So then, they come for that visit and what you mentioned was just spot on, getting a list of questions together. What we do at my institution, as well as many throughout the country, is a process called shared decision-making.  

You might’ve talked about this on prior webinars, but shared decision-making occurs when that healthcare team, such as the physician, nurse practitioner, pharmacist, whoever, shares information with the patient and their care partner.  

You mutually share information to arrive at a decision. So, many studies have been done on shared decision-making. It’s done in many different areas. And so, through that sharing of information, you might think of different questions.  

Some of the things that I try to proactively offer – we all have our list of things that we educate our patients on, but some of the things I proactively will recommend to patients and their care partners when you’re seeking an opinion at these centers is, “How long will I be sick? What are the biggest side effects of the medication I have to worry about?” Asking your care team – I know it sounds silly, but are they aware of all your prior health concerns, especially if you’re coming for an evaluation.  

Maybe you have peripheral neuropathy where you have numbness and tingling in your fingers or toes or a history of kidney disease. Your kidneys look fine now but maybe a few years ago at the myeloma diagnosis the kidneys had a temporary failing and now they’re better so they’d want to protect you with future medications. How long will you have to take medications after the CAR-T procedure? There’s antiviral medicines, antibacterial medications, and medications called IVIG, which strengthens your immune system.  

And then, finally, asking about the infection protection afterwards. Do you have to get vaccinated again against pneumococcal, shingles, and all of those other things that we do. The cellular therapy guidelines suggest timepoint for one, three, five, etc., months after CAR T-cell procedure to get revaccinated. So, who’s going to do that for you?  

How are you going to know what to get? So, make sure that they give you a timeline, calendars, and set expectations for what you need to do as a patient and then you’ll help them set expectations for what they need to do to provide you the accurate education.  

Katherine Banwell:

Well, talking about what to expect after CAR T-cell therapy, would you tell us what some of the potential side effects are?  

Dr. Beth Faiman:

Oh, absolutely. So, CAR T-cell therapy – again, it harnesses your immune system using your T cells. Your T cells are so important in your immune system to be programmed as fighters. And as people age, or as long as – after they’ve had myeloma or other kinds of cancers, those T cells just don’t work as well. So, what we want to do is engineer them and program them with what we call a viral vector to be fighters. So, those T cells, as I mentioned, are harvested, stored, and then manufactured to go. 

And I tell people it’s like that Pac-Man video game. It goes around in your bloodstream just kind of eating away at the myeloma cells. So, you don’t take any medications. You don’t go in for IVs every week or twice weekly, or taking pills at home to treat the myeloma. It’s what we consider a one-and-done thing. So, if it works for you, it can keep you in remission for quite some time. But if it doesn’t work then there still are other therapies down the road.  

So, the CAR T-cell therapy is something that is an option but there are other therapies out there in many cases. There’s something called a bispecific antibody. There are three currently approved for multiple myeloma now. So, maybe a CAR T-cell therapy doesn’t seem right for you because you’re not in a good remission or the cancer’s too active right now so you don’t have the time to wait for manufacturing of the cells and putting them back in your bloodstream.  

Those bispecifics will fill that gap. So, when you’re discussing the options, aside from clinical trials and other drugs, the bispecific antibody is very similar. One of the things that I wanted to highlight is that nowadays we’re into these things called sequencing. So, we’re trying to figure out what order to give these super effective drugs. Should we give the bispecific antibodies first or should we give the CAR T-cell therapy first? And in most centers, if you have time to wait and you’re planning, the CAR T-cell therapy is right for most people and then the bispecifics would come later.  

Katherine Banwell:

All right. So, after CAR T-cell therapy is completed, what potential side effects might people experience, and what should they look for?  

Dr. Beth Faiman:

Absolutely. I think of things in short-term and long-term side effects. So, the short term, you’re going to be admitted to the hospital and you have a risk for – when we get those T cells back – that cytokine release syndrome, or it’s abbreviated CRS – where you’re body’s immune system’s fighting.  

I tell folks it’s kind of like if you got a vaccine for a flu vaccine or pneumonia and you had a reaction it’s just way worse. So, you can get a high fever – the big first sign of this CRS. Usually, the providers will jump in with giving you a medication called tocilizumab (Actemra) or a similar drug that blocks IL-6, which is a chemical that is triggered when we get the CRS. And then, it stops those symptoms. And so, most of us know how to do that and will approve your insurance to get access to that tocilizumab or similar drug when we approve your CAR T-cell therapy.  

So, that CRS can get you really, really sick. You can get low oxygen levels in your blood. You can get a high fever and you can drop your blood pressure. But most CAR T-cells centers, the nurses and the staff are very well-trained to monitor this every eight hours, in most cases.  

Another rare side effect we worry about is ICANS and it’s a neurotoxicity kind of thing.  

It can be with CRS or without CRS. But they’ll ask you to do things like write your name on a piece of paper every eight hours or tell me – draw a clock or count backwards from 100. And so, if you have any deviation, even minor, from what you reported back beforehand then we worry about neurotoxicity. Now, that’s short term but that’s the reason why you can’t drive a car for 30 days is because it could be delayed. 

The CRS can start with the one thing, the ide-cel usually occurs within one day so most people are admitted to the hospital for that CAR T-cell therapy. The Cilta-cel, it onsets to about seven days. So, some people get the cilta-cel outpatient and then are monitored daily, whether in person or through virtual telehealth monitoring.  

But at any rate, those are the short-term. Long-term, we worry about low blood counts maybe for the first month afterwards. And then, those will come back to normal. And then, we worry about infection. So, I mentioned the antibacterial, antiviral, which is usually a medicine called acyclovir (Zovirax), which most myeloma patients will have been on anyhow. And then, that IVIG to protect against viruses and bacteria when your immune system is so low. 

But fortunately, if we control the CRS, it usually comes with the CRS, although it can be independent. We try not to give steroids, because we don’t want it to interrupt the CAR T-cell process. But many institutions will give that tocilizumab for ICANS. And if that doesn’t get better then they’ll give you a steroid, such as dexamethasone (Decadron). 

And so, that will usually reverse itself pretty quickly. Longer term, after 30 days, you can get with the Carvykti, particularly something called Parkinsonian things where you can get a little bit shaky or something like that. Again, it’s very rare and I have had hundreds of people who have undergone the CAR T-cell procedure at my institution. And knock on wood, fortunately, I’ve not seen first-hand that side effect. And I think it’s because we’re so good now at treating the – preventing the ICANS and CRS as best as we can while they’re inpatient and doing real close following.  

One other thing I want to note is if somebody who’s watching this does go in the hospital for any reason, get up and walk around and stay strong, as well as you can, during the procedure. You might be bored if you’re in the hospital anyhow, but try to stay as strong as you can in the hospital. It’ll help your post recovery for sure.  

Katherine Banwell:

Well, what about more mild side effects like fatigue and changes in appetite?   

Dr. Beth Faiman:

Absolutely. So, the fatigue and the changes in appetite are generally mild for most but I see it, in my experience, if your myeloma’s acting up really quickly, if you’re having a rapid disease progression, the medications that we give you to control the myeloma during this bridging therapy phase might cause some of that as well, not necessarily the CAR T-cell process. But think about it. We’re using your own cells engineered to be fighters.  

And so, that first month or two is probably when you’re going to be the most tired as your body is being programmed to fight against the myeloma cells. That fatigue tends to get better. And as I mentioned just a moment earlier, the importance of just walking around in the halls, getting out of bed when you’re in the hospital, that can really help your post recovery. It doesn’t seem like much, but there have been many studies about how muscle mass declines, energy declines when you’re hospitalized.  

And we want you to be as strong as you can and thrive as much as you can for when you’re out you can then do the things you want to do at a quicker pace.   

Katherine Banwell:

Right. That’s great advice. Beyond monitoring of any issues, what can someone expect related to returning to life as they knew it before the diagnosis? Is there a timeline for resuming lifestyle and activity?  

Dr. Beth Faiman:

Yeah. So, I should say I because it’s from my perspective. I am a real strong advocate. I tell people to do what you feel like you can physically do. We know that myeloma can affect the bones and put your bones at risk for breaking and so we give you medicines to protect it. So, I do put some restrictions however on physical activity in terms of, “I don’t want you to bench press 40 pounds or 20 pounds,” in most cases. And depending on what the bones look like on x-ray, I’ll even restrict it to about five to 10 pounds.  

If you think about it, that’s a bag of potatoes. So, you don’t want to put too many restrictions on for everybody. But talk to your healthcare provider about what your specific restrictions are with physical activity. Because I don’t really put any restrictions on but I encourage things like riding a bike, especially a stationary bike in your own home, so that if you fall off – hopefully, you won’t fall off a stationary bike. But if you injure yourself, then you’re able to be in a place that somebody can help you.  

But riding a bike. Also, exercising in water. Water therapy is a great weight bearing exercise and there are times of day where you can go when the YMCAs or YWCAs aren’t as busy – or community centers. So, you’re less at risk for bacterial or other illnesses. But during that first month, I try to limit their exposure to people because you’re at risk for the different viruses that are all over the place, the bacterial infections. 

So, that first month is the critical period where I try to say, “Okay, try to lay low. Let’s get you through this period. Your immune system will start getting stronger on its own after this period.” And then, that month two you start feeling like doing more. You go to the grocery store. You maybe go to eat out at a restaurant but pick a time of day that’s less busy. So, go for an early dinner. There’s no shame in eating at 5:00 p.m. if you want to go out. And then, get a table in the corner with your own wipes. And so, that’s where your immune system is getting stronger. 

And then, by month three, I think most people will feel much, much better and much, much stronger. And if you can keep moving throughout this whole time, then you’ll be stronger on the way out.  

Katherine Banwell:

Dr. Faiman, from what you’ve described, undergoing CAR T-cell therapy can be a very intense process. Why would someone consider this option over another myeloma treatment option?  

Dr. Beth Faiman:

Yeah. So, the CAR T-cell therapies have really transformed myeloma, in my opinion.  

When we first started using CAR T-cell therapies, there was a long wait list because people who had had three, five, seven, 10, 12 prior therapies, they had very few other options. So, we had ethically assigned scores to people as to who – we’d get one or two slots a month and then we’d have 80-some people on this list. And we’re thinking, “How do we allocate who’s going to get this therapy?” And it’s because you can have a nice, long remission off of all therapy.  

It’s a great, great option for most people. Again, I would hope that we can get this moved further into the disease trajectory. There are actually two studies. One was a KarMMa study. It was published in the New England Journal of Medicine in 2023, early part of 2023.  

And it showed that when people get this therapy earlier, the Ide-cel first, you can have a longer remission. So, we’re talking about three, four, five or more prior lines of therapy you can get about 11 months with the Ide-cel.  

You could even get a longer remission off of all therapy if you move it earlier. Same with Cilta-cel. We had studies and different cohorts and you can be in a long remission. So, think of somebody who’s – myeloma’s incurable. It’s very treatable but it’s incurable for most. And so, you go from the expectation of staying on treatment until disease progression, much like other chronic conditions like diabetes. We don’t stop medicine for diabetes or high blood pressure.  

And it’s the same with myeloma and many of the cancers that we treat these days. And so, a CAR T-cell therapy will give patients the option of having that disease free interval where you can go and travel the world. I have patients that have bought RVs after their CAR T-cell therapy and now they’re going around the world – well, not the world. But around the United States.  

Katherine Banwell:

The country. 

Dr. Beth Faiman:

The country. And just really enjoying life and taking that time off and being realistic, knowing that we have to do bloodwork every month to make sure the myeloma’s still in remission because it can come back. But at least it’s sleeping for right now. So, you can go out and enjoy your life and take those trips and enjoy the little things and the big things.  

Katherine Banwell:

Yeah. Well, thank you for that advice. I’d like to get to a few audience questions that were sent in prior to the program. Alice asks, can you share more information about T-cell collection? A recent webinar mentioned that myeloma must be in good control. Can you share specifics about the bridging therapy prior to infusion?  

Dr. Beth Faiman:

Yes. So, again, the process is the lengthy process as we mentioned before. But for the actual T-cell collection, we will have approved you to get the therapy. Financially, we’ve cleared you. Socially, you’ve gotten your support systems and now we’re getting those cells out.  

We use a process called apheresis where a temporary catheter is placed under the skin, and it separates your white blood cells and then returns the red bloods and plasma back into the blood. And it sorts out those T cells. The process itself, you’re on the machine for anywhere for two or three hours. Hopefully, it’ll just be one day’s time. And then, they’ll manufacture those cells.  

So, during that period where we’ve put your cells and sent them away to wherever’s going to be doing the manufacturing, you’re going to need to get a treatment that’s going to keep you in remission from the myeloma. And it’s not going to prevent you from getting those cells safely back. So, we don’t want anything that’s too toxic for most people. So, what we’re doing now is we have that information that early on is better for myeloma to get these treatments. And so, the hope that bridging therapy won’t be as common of a thing anymore.  

Because now we’re selecting people that are – the myeloma’s just starting to act up. Let’s get those cells out, send them off, so we don’t have to do bridging therapy. We can just keep you – add a medication or take away another medication to keep you in remission. So, that’s the goal of bridging therapy. What’s that bridge to get your cells back in for some people? It might be a chemotherapy type of a thing. But for other people it’s just trying to get you that CAR T-cell collection and manufacturing so we don’t really have to change everything all up.  

And we’ve been very fortunate now that the wait lists have cleared in most institutions. CAR-T cell is available at more centers across the country and so we don’t have that backlog. And so, fortunately, bridging therapy will hopefully be a little bit less of a thing.  

Katherine Banwell:

We have another question. This one from Rita. What kind of monitoring takes places in the months following CAR T-cell therapy and what kinds of medicines are required afterward?  

Dr. Beth Faiman:

Oh, excellent. So, the monitoring is usually on the short-term, within the first 30 to 60 days afterwards, oftentimes depending on what your blood counts are showing. You might have to get blood counts tested more frequently. So, that complete blood count shows you the white cells, the red cells. The white cells fight infection. Red cells carry oxygen. Platelets clot the blood. That’s a marker of how well your bone marrow is functioning. It also can be – those innocent bystanders can go low temporarily after this procedure.  

So, definitely those CBCs need to be tested, for some people weekly and for some people every other week. And your healthcare team will tell you how often. After that first two to three months and your blood counts are all in good shape, then we can just go oftentimes to a monthly monitoring of the myeloma labs. So, that’s the CBC and the chemistry panel but also the paraproteins in the blood and the urine get monitored.  

There’s also another test called a CD4 count that’s something that you wouldn’t have had beforehand. The CD4 count is an immune count that we want to be over 200. Oftentimes,  you’ll be on an antibiotic called Bactrim or an inhaled called pentamidine to lessen the chance of a certain kind of infection called PJP, or pneumocystis. So, those are those atypical infections that we’re now seeing with CAR-T cell and other therapies.  

And as I mentioned, acyclovir to protect against shingles is a medication but you’re not going to be on any anti-myeloma medications other than maybe a bone strengthener if you get that intermittently. Fortunately, after CAR-T cell, you don’t have any anti myeloma therapy as long as you’re in remission.  

Katherine Banwell:

We also received this question from a viewer named Rob. If you receive CAR-T therapy, how long does it last and have you seen remission for a long time?  

Dr. Beth Faiman:

So, I’d like to tell Rob that I’ve seen a little bit of a remission and I’ve seen long-time remissions. Unfortunately, it goes back to the biology of the disease. People that have a more aggressive type of myeloma tend to not have as long of a remission but that’s not always the case. So, if you have what’s called a standard type of myeloma, which fortunately about 80 percent of the people have a standard or good type of myeloma, you can get an 11- to 24-month remission if you’ve had many prior therapies.  

Now, if we’re moving the CAR-T earlier lines of therapy, as in those two studies that I briefly mentioned with the Ide-cel and the Cilta-cel studies that are moving it to one to three prior lines of therapy, people are getting longer remissions.  

Unfortunately, I do not have a crystal ball. I can look at your disease genetics. I can look at how deep your remission status is and I can generally predict based on other studies how long of a remission you might get, but it’s not a guarantee. What works for one person might not work for the other so you take it with a grain of salt. We just say, “Gosh, this is a great therapy. We need to offer it to you while we have that window of opportunity. You’re in a good remission. We have a slot for you. We’re going to pick the best product for you. Let’s give you this option.” 

You might be one of those exceptional responders that are in remission for several years, which I do have people that have been in remission several years, fortunately.  

Katherine Banwell:

Okay. Well, thank you so much for the thoughtful responses to those questions. As we close out today’s program, can you talk about some of the ongoing research in CAR T-cell therapy and what you’re excited about?  

Dr. Beth Faiman:

Oh, my gosh. I am so excited about CAR T-cell therapy research. There are these what we call CRISPR gene edited technology, which is really personalizing the treatment in CAR-T.  

There’s what we call an off-the-shelf approach where we don’t have to manufacture one’s T cells to be a fighter. So, these CAR T-cell therapies are the kinds of clinical studies where if you are in a position where you want to hopefully get an earlier access to a great therapy, this CRISPR edited at – Caribou is what it’s called, that we have at my institution. That might be right for you.  

There’s also the different targets. For example, the Ide-cel and the Cilta-cel target what’s called BCMA or B-cell maturation antigen. Basically, the BCMA is expressed mostly on cancer cells and less so on healthy cells.  

And so, that’s what the target is for these current CAR-Ts. We have different targets. So, what does that mean for you? If you had a CAR T-cell therapy against BCMA or a bispecific against BCMA now we have these different targets so that gives you other options for remissions status. So, if you can, I am a big, strong advocate for clinical trials. Like I said, it’s getting better access. You have a healthcare team. There’s so much stigma associated with clinical trials, but every single person is a candidate for some sort of a trial or another.  

So, talk to your healthcare team or you can go to clinicaltrials.gov and then all the patient care organizations – International Myeloma Foundation, Multiple Myeloma Research Foundation, has access to clinical trial information as well for patients. So, yes, lots of good things. New targets. Off-the-shelf so you don’t have to manufacture. So, that represents new treatment options for many patients.  

Katherine Banwell:

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

Dr. Beth Faiman:

My pleasure. Thank you for having me.  

Katherine Banwell:

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

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

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

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

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

See More from Evolve Myeloma

Related Resources:

Considering CAR T-Cell Therapy for Myeloma_ Key Questions to Ask Your Doctor

Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023

Transcript:

Dr. Timothy Schmidt:

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

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

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

What Should Myeloma Patients Ask About Developing Research?

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

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

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

See More from Evolve Myeloma

Related Resources:

Myeloma Research Highlights From ASH 2023

Myeloma Research Highlights From ASH 2023

How Is Bispecific Antibody Therapy Changing Myeloma Care

How Is Bispecific Antibody Therapy Changing Myeloma Care?

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

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

Transcript:

Dr. Timothy Schmidt:

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

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

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

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

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

Myeloma Research Highlights From ASH 2023

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

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

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

See More from Evolve Myeloma

Related Resources:

What Should Myeloma Patients Ask About Developing Research

What Should Myeloma Patients Ask About Developing Research?

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

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

Developing Research and New Myeloma Treatment Options

Developing Research and New Myeloma Treatment Options

Transcript:

Dr. Timothy Schmidt:

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

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

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

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

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

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

Evolve Myeloma Resource Guide

Download Resource Guide

PEN-181_EvolveMMResourceGuide_F

Download Resource Guide

See More from Evolve Myeloma

Making Treatment Decisions | Understanding Common Myeloma Therapies

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

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

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

Download Resource Guide

See More From INSIST! Myeloma

Related Programs:

How Close Is Personalized Medicine for Myeloma?

How Close Is Personalized Medicine for Myeloma?

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

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


Transcript:

Katherine:

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

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

Dr. Rosko:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

How Do Myeloma Test Results Influence Prognosis and Care?

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

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

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

See More From INSIST! Myeloma

Related Programs:

How Close Is Personalized Medicine for Myeloma?

How Close Is Personalized Medicine for Myeloma?

What Tests Are Essential to Understand a Myeloma Diagnosis?

What Tests Are Essential to Understand a Myeloma Diagnosis?

Making Treatment Decisions: Understanding Common Myeloma Therapies

Making Treatment Decisions | Understanding Common Myeloma Therapies


Transcript:

Katherine:

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

Dr. Rosko:

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

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

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

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

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

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

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

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

Katherine:

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

Dr. Cottini:

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

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

Accessing Personalized Myeloma Treatment | What Patients Should Know

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

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

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

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

Download Resource Guide

See More From INSIST! Myeloma

Related Programs:

What Should You Ask Your Doctor About Myeloma Testing_

What Should You Ask Your Doctor About Myeloma Testing?

How Is Myeloma Treatment Response Measured?

How Does Essential Testing Affect Myeloma Care and Treatment (1)

How Does Essential Testing Affect Myeloma Care and Treatment?


Transcript:

Katherine:

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

Dr. Rosko:

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

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

Katherine:

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

Dr. Cottini:

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

Katherine:

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

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

Dr. Rosko:

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

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

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

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

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

Katherine:

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

Dr. Cottini:

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

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

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

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

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

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

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

Katherine:

What is cytogenetics? 

Dr. Cottini:

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

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

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

Katherine:

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

Dr. Rosko:

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

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

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

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

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

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

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

Katherine:

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

Dr. Cottini:

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

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

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

Katherine:

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

Dr. Rosko:

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

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

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

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

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

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

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

Katherine:

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

Dr. Cottini:

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

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

Katherine:

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

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

Dr. Rosko:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Katherine:

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

Dr. Cottini:

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

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

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

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

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

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

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

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

Katherine:

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

Dr. Cottini:

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

Katherine:

Dr. Rosko? 

Dr. Rosko:

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

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

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

Katherine:

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