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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

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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.  

Thrive | What You Should Know About MPN Symptoms & Treatment Side Effects

Thrive | What You Should Know About MPN Symptoms & Treatment Side Effects from Patient Empowerment Network on Vimeo.

How are MPN symptoms and treatment side effect managed? In this animated explainer video, an MPN specialist and myelofibrosis patient discuss the importance of clear communication with your healthcare team, the process for assessing common issues, and advice for advocating for yourself.

 

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Myeloproliferative Neoplasm News and Research Updates

How Molecular Markers Affect MPN Treatment | Advances in Research

How Molecular Markers Affect MPN Treatment | Advances in Research


Transcript:

Brian: 

Hi, I’m Brian. Nice to meet you! I’ve been living with a condition called myelofibrosis for many years. While there have certainly been ups and downs, I’ve been able to navigate care for my condition and to live a full life.  

So how have I been able to do that? First and foremost, I have a great relationship with my care team, whom I communicate with regularly. Meet, Dr. Liu – my doctor. 

Dr. Liu: 

Hi! I’m Dr. Liu, and I’m a hematologist and a specialist in myeloproliferative neoplasms or MPNs. The three types of MPNs are essential thrombocythemia, or ET,  polycythemia vera or PV, and myelofibrosis, or MF.  This group of blood cancers is characterized by the bone marrow overproducing a certain type of cell.  

Maintaining a good relationship with your healthcare team, coupled with finding a treatment approach that works for you, can help you live a full life and to thrive with an MPN. 

Brian: 

Exactly, Dr. Liu. Over the years, I’ve experienced periodic issues with my condition. I’ve had symptoms and treatment side effects that have been bothersome and interfered with my life. But, communication with my team has been essential to feeling well.  

Dr. Liu: 

That’s right, Brian. When symptoms or treatment side effects are bothering you, it’s important to let your healthcare provide know how you are feeling. 

Brian: 

For example, recently I felt tired beyond general sleepiness. And when I shared this with Dr. Liu, we discussed potential causes of the fatigue, and we talked in-depth about my options to manage it, including changing therapy and some simple changes to my diet and lifestyle.1 Over time, my energy levels improved, but having the open dialogue with Dr. Liu was essential to tackling this symptom head-on. 

Dr. Liu: 

That’s a great example. When I first hear from a patient that they are having an issue, we go through several steps to find a solution.2  

We start by ensuring that the disease is well-controlled, so we check blood counts. Next, we try to determine if it is a symptom of the MPN or a side effect of the treatment. Once we’ve done those steps, we come up with potential solutions which may include, but are not limited to: 

  • A dose reduction or a treatment holiday. 
  • Changing therapy to find something that is more well-tolerated. 

Other considerations are dependent upon the specific symptoms and side effects but may include: 

  • Supportive care options, including diet and exercise. 
  • A visit to your primary care doctor to see if there is something else going on physically. 

Brian: 

That’s good to know, Dr. Liu. Something you brought up with me, which I feel is important to mention, is mental health. Often, emotional symptoms can take a toll on the body, causing fatigue or other issues. 

Dr. Liu: 

Great point, Brian. Seeking care for your mental health is crucial, particularly if you are in active treatment. 

Brian: 

Of course, we know that the symptoms and treatment side effects for MPNs can vary widely, so what advice do you have for patients who may be afraid to speak up? 

Dr. Liu: 

The most important thing to remember is that we have options to help you, no matter what you are going through. It’s your body and if you don’t let your provider know what you’re going through, they can’t help you. 

Brian: 

So true. It’s also a good idea to bring a care partner along to appointments, sometimes a spouse or friend can you help you communicate what’s going on. 

Dr. Liu: 

That’s great advice, Brian. Bringing someone along to take notes is a great idea. Also, be sure to write down any questions or concerns you have in advance to make the most of your appointment. 

Brian: 

OK, Dr. Liu, let’s recap your advice for MPN symptom management: 

Dr. Liu: 

Good idea! First, remember that everyone’s MPN is different, so managing symptoms and side effects can be tricky. Communicating with your healthcare team is critical to your overall care – report any and all concerns to your team immediately. 

And, do your part. Make sure you see your primary care physician regularly and do your best to maintain a healthy lifestyle. 

Brian 

And, most importantly, remember you are at the center of your care. Never hesitate to share your opinion and to advocate for yourself. 

To learn more, visit powerfulpatients.org/MPN to access a library of tools. Thanks for joining us! 

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

 

Dr. Adriana Rossi, a myeloma expert and researcher, discusses how CAR T-cell therapy has revolutionized care, the process for undergoing this therapy, common side effects of this treatment, and advice for patients considering this option. Dr. Rossi also shares updates in CAR T-cell therapy research and explains what she’s excited about in myeloma care.

Dr. Adriana Rossi is Co-director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.

Download Resource Guide

See More From Thrive CAR T-Cell Therapy


Transcript:

Katherine Banwell:

Hello, and welcome. I am your host, Katherine Banwell. Today’s program is part of our Thrive series, where we will discuss what to expect and how to manage side effects of CAR T-cell therapy.  

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. Adriana Rossi. Dr. Rossi, welcome. Would you please introduce yourself?  

Dr. Adriana Rossi:

Thank you so much. I am one of the codirectors of the CAR T program at Mount Sinai in New York City and thrilled to be with you today.  

Katherine Banwell:

Thank you. Since we’ll be discussing the ins and outs of CAR T-cell therapy, I thought we could start with your perspective as a researcher in the field. How has this therapy revolutionized myeloma care?  

Dr. Adriana Rossi:

It absolutely has. And I would say in time we’ve had – this is now our fourth revolution. Stem cell transplants was the first time we actually achieved what we call a complete remission in at least a few patients, making myeloma disappear.  

Then, we had the second revolution with the novel agents. Now, we had drug therapies that were giving us these complete remission still at about a 30 percent rate. And then, the monoclonal antibodies were the most recent revolution. And currently, we are in what we call the T-cell redirection.   

It really has been driven by CAR T-cell therapies and something we call bispecific antibodies, which also use your patient’s T cells to kill the myeloma. We are now seeing absolutely unprecedented response rates, meaning almost everybody is responding. Also, depth of response, which we have really learned over time is a way to translate into long remissions. So, every long, very significant remissions. And the early data in patients who have had many prior lines.  

Katherine Banwell:

So, it is very encouraging news.  

Dr. Adriana Rossi:

It is very encouraging.  

Katherine Banwell:

Let’s start with an overview of CAR T-cell therapy. Could you explain how the treatment works?  

Dr. Adriana Rossi:

Absolutely. So, CAR T specifically is speaking to T cells, which are a normal part of the immune system that have been engineered and modified. So, normal part of the immune system T cells have a lot of checks and balances and are constantly looking for cells that are supposed to be killed. For example, something that has a virus in it.  

When we engineer the CAR T-cells, we modify, one, the target so they are now trained to find the specific target on a tumor cell. And we remove all these checks and balances. So, once that T-cell finds its target, it can kill it without all of the side effects. The way normal T  cells communicate with other members of the immune system are something called cytokines. So, we will touch on that a little later, I think, but we also, again, interfere with that communication by engineering the cells.  

Katherine Banwell:

Which patient type qualifies for CAR T?  

Dr. Adriana Rossi:

In 2023, we currently have two approved commercial CAR T products and we do have a number of them in clinical trials. The two that are commercially approved specifically are targeted for patients who are in their fourth line of therapy, so the myeloma has learned to come back that four times.  

They’ve been exposed to all of the regular drugs, which by four lines most patients will have been at least once. We look for patients whose kidney function is at a safe level to tolerate the therapy. And other than that, it’s really having caregiver support and overall ability to come to a center that specializes in this.  

Katherine Banwell:

What’s the process for accessing the CAR T?  

Dr. Adriana Rossi:

The first important part is remembering they exist and having the referring physician remember to send patients our way. Once patients come to our center, they will meet with coordinators, both the clinic coordinators to make sure we have all of the testing, to make sure the heart is healthy enough, the lungs are healthy enough. There’s no infections brewing.  

Financial coordinators to take care of all of the organizing. If patients are coming from further than 30 minutes, setting them up for a place to stay in the city, transportation aid, all of those things. Once we decide to go ahead and have our collection date set, that sort of starts the actual process. Since most of our patients have had stem cell transplants before, there is that point of comparison. I think one of the most important things to remember is CAR T is not stem cells.  

So, while they’re both the cellular therapies, the patient experience is vastly, vastly different. It starts with a collection, where in stem cells you need several days of injections and maybe several days of collection. T-cell collection is a one-day event. We get what we get and then we are going to manufacture them and we can grow them in a Petri dish. There is no minimum and there is no instigating injections to get them going.  

Once they’re collected, the cells are then sent for manufacturing, which may take from four to eight weeks. During that time, patients usually receive what we call a bridging therapy, which is some kind of therapy to keep the myeloma at bay. Not to get rid of it but to keep it under control so that once the cells are ready the patient is also ready. Going into CAR T with growing myeloma can increase the side effects.  

Katherine Banwell:

Go ahead.  

Dr. Adriana Rossi:

I will give you just the final bit. Once the cells are ready, then we plan to give chemotherapy to get the patient’s T cells to not put up a fight. That’s called lymphodepletion. We infuse the cells and they’re now with us for two weeks in the hospital and usually two weeks after.   

Katherine Banwell:

Okay. So, I was going to ask how long patients are in the hospital for the procedure. So, that explains that. So, it is about two weeks. What signifies that a patient is ready to be released and go home?  

Dr. Adriana Rossi:

The reason patients are in the hospital is a very classic expected toxicity experience. So, they’re in the hospital for us to observe, watch. If it happens, which about 80 percent of the time there will be some toxicity for us to address – one that toxicity has resolved, they’re then okay to go home.  

Katherine Banwell:

Okay. That is great advice. Thank you. Of course, we know that CAR T-cell therapy comes with some potential side effects. Let’s talk about some of those side effects and how they’re managed. You mentioned cytokine release syndrome earlier. Let’s start with that. What is it, exactly?  

Dr. Adriana Rossi:

Yes. As I mentioned, cytokines are molecules that the cells of the immune system use to communicate with each other. With this therapy, we are asking the T cells that have been infused to expand, meaning make multiple copies of themselves, and sweep through the body looking for myeloma and basically picking a fight with them.  

So, CRS is what happens when the T cells are too good at their job and they overachieve and then picking a little fight kind of make a big ruckus. The result is what we call inflammation, which the patient will experience usually as a fever.  

But if it does not go – if it continues to go unchecked, that fever can be accompanied by low blood pressure because of these inflammatory markers, difficulty breathing or low oxygen levels. And all of these things are now vastly prevented. CRS is usually treated very quickly and doesn’t get to these higher grades, more complicated fields.  

Katherine Banwell:

How is CRS managed?  

Dr. Adriana Rossi:

We have a couple of very good antidotes. CRS by itself is not just a fever. Certainly, a fever in any patient who is undergoing these kinds of therapies, we will try to rule out any infections. But there are markers in the blood that we can follow. When the blood markers and the fever occur at the same time, we know that cytokines are driving that effect. If it seems to be driven by something we call IL-6, we use tocilizumab (Actemra). If it seems to be driven by IL-1, we use anakinra (Kineret). These are all drugs that are themselves monoclonal antibodies which then will shut down that overreaction and cool things down.   

Katherine Banwell:

Okay. Another possible side effect is neurotoxicity. Would you define that term for us?  

Dr. Adriana Rossi:

Yes. That one is harder to define because neurotoxicity in itself is very broad. We usually think of something called ICANS, which is the neurotoxicity associated with the effector cells. That specific neurotoxicity tends to happen in conjunction with CRS.  

And while CRS probably occurs in about 85 percent of patients, the ICANS is usually in the order of 5 percent. So, much, much more rare. And the antidote for that, which most patients know, love, and hate, is steroids.  

Katherine Banwell:

Ah, yes.  

Dr. Adriana Rossi:

I should mention there are other parts of neurotoxicity which I think the most concerning is something that has been known as Parkinsonian symptoms. It’s really just movement disorder. These are exceedingly rare and so we haven’t had a chance to learn very much because there are so few patients who have had this complication. We have learned from the first six patients who had this how to avoid it. And so, I think it’s now even more rare and it really goes into patient selection, to making sure, as I mentioned, that the myeloma isn’t growing very much.  

We monitor to see if the T cells grow too fast, if the CRS is of a high level. These are all predictors of delayed neurotoxicity.  

Katherine Banwell:

What are the signs of neurotoxicity in a patient?  

Dr. Adriana Rossi:

Very specifically, for the ICANS, we have tool called the ICE tool, which is a series of questions to test memory and attention and ability to write and understand and speak. So, most commonly, it would be an inability to speak properly or, if someone is writing a sentence, it’s really a very classic finding. It is no longer spread across the page.  

These are not subtle findings. Part of, again, being in the hospital is to allow us to have this tool twice a day and look for these signs very early on, interfere with their development by giving the patients steroids – usually for a day or two – and resolving it.  

Katherine Banwell:

So, that’s how neurotoxicity is managed, then.  

Dr. Adriana Rossi:

Yes.  

Katherine Banwell:

And is there a potential for long-term issues associated with neurotoxicity?  

Dr. Adriana Rossi:

Certainly, there is always the potential. But the vast majority – again, the ICANS tend to be self-limited while the patient’s in the hospital, and that is why we’re watching during that window. The delayed neurotoxicities, in addition to these very rare movement disorders, we do see some cranial nerve palsies. The seventh cranial nerve, usually recognized as Bell’s palsy, has happened a few times. We really don’t understand the mechanism of what is driving it. It’s inflammation but why there, why that way. So, we tend to use acyclovir, which is the classic treatment for Bell’s palsy and steroids.  

Katherine Banwell:

Dr. Rossi, a suppressed immune system is something that a patient undergoing CAR T-cell therapy should consider. What does it mean and what precautions should patients take?  

Dr. Adriana Rossi:

That is such a good question and it is specifically true for patients who are receiving therapies that target BCMA, which both commercial CAR Ts at the moment target.  

Because it is such an effective therapy at bringing down cells that express BCMA, your immune cells that make antibodies, one of the side effects is the immunoglobulins, which are the antibodies, are all very, very low. So, that is one level of immunosuppression.  

The other is the chemotherapy that we use to quiet the T cells can also lower all the blood counts. So, red blood cells and platelets may be low as well and those are not involved with immunity and can be transfused. So, that is a supportive mechanism. For the immune therapies, we usually use IVIG, which is intravenous immunoglobulins to support the patient until they’re able to make their own.  

We also protect them from viral infections with acyclovir or valacyclovir. Protect them from something called PJP pneumonia, which is a virus that specifically appears when you’re very immunosuppressed. Should their neutrophil count be low, that is another type of white blood cell – make sure they’re protected with antibiotics.  

Katherine Banwell:

Is there a typical timeframe for the immune system function to return?  

Dr. Adriana Rossi:

I would say a year is a good time but it’s a very unpredictable wave. So again, unlike stem cell transplant where you have a clear time where the cells are low, they recover, they stay recovered, we have noticed for some patients, they may have low blood counts just during the first month and then be recovered. Some will have no problems in the first month and it’s in the weeks to follow that suddenly either the reds, or the platelets, or the white count may need support.  

And in very rare instances, out to a year, they’re still needing support, sometimes say a growth factor injection once a week.  

Katherine Banwell:

So, how is it monitored over time?  

Dr. Adriana Rossi:

We monitor all those different levels of the immune system. So, we check on the CBC, which is the very common blood counts. We also look at what is called a lymph panel to look at the different types of T cells and make sure that they are recovering. Those usually take about three to six months to recover. The white count, again usually by Day 30, but there are some cases of delayed recovery. And the immunoglobulins, which is the antibody level, we also monitor monthly.  

Katherine Banwell:

What other side effects should patients who are considering CAR T-cell therapy be aware of?  

Dr. Adriana Rossi:

Really, those are the big three. I would say others are very rare but the low blood counts is the one that lasts beyond the time in the hospital. And the rare neurotoxicities that are delayed.  

Katherine Banwell:

When should patients mention any issues they’re experiencing to their healthcare team?  

Dr. Adriana Rossi:

Always. That is a very, very, short answer. Please don’t ever think you are bothering the doctor. I hear that a lot. “Oh, I didn’t want to bother you.” It is never a bother. This is why we are here. So, anything that is happening that is out of the ordinary, please let your healthcare provider know. If it is not something that needs our attention or we don’t need to worry about, we will tell you.  

Katherine Banwell:

Better safe than sorry.  

Dr. Adriana Rossi:

Always.  

Katherine Banwell:

And how does a care partner factor into the process? It seems having a good support system is essential.  

Dr. Adriana Rossi:

It absolutely is. I think the entire journey of myeloma really is what I would consider a team sport. It is not something we go through alone. And the more members of the team you have the better. So, as your medical team, we always value the caregivers. For CAR T specifically, since there is this concern for infections and neurotoxicity, caregivers are really essential. They should be well informed, know what to look for, and be the ones to reach out to us if anything is concerning. Again, any symptoms out of the ordinary, any fever, and really be a part of communicating with the medical team.  

Katherine Banwell:

Is there a period where patients are considered out of the woods from CAR T side effects?   

Dr. Adriana Rossi:

Hard to say. Again, I like to emphasize that most patients by Day 30 or 60 are back to work, are feeling themselves, are recovered. Another contrast to stem cell transplants. It’s a much faster recovery. I have patients who within 30 days are eager to go back to work and don’t know what I was talking about or why I insist on seeing them so much.  

But some patients, again, out to a year, may still be requiring visits for support in either the IVIG for the immunoglobins, growth factor support for their counts. So, there are outliers at both extremes. We follow the model of 100 days for recovery.  

Katherine Banwell:

Do some patient types do better than others?  

Dr. Adriana Rossi:

Well, always yes. And we are still endeavoring to figure out who they are and why that is. There are things that we don’t know, can’t predict. But things that we do recognize are again bringing patients whose myeloma is under good control.  

So, instead of having a lot of disease or disease that is in a growth phase, we try to use the bridging therapy to optimize the patient, not only to improve the response, but also minimize the toxicities. 

Katherine Banwell:

Does age have an impact at all?  

Dr. Adriana Rossi:

Not as much. We actually have just finished an 88-year-old patient whose hospital course was remarkably unremarkable, as we would like. I think another difference from stem cells, it is not as rigorous. While each patient, I think, should be part of that decision and that conversation, reviewing what is now a growing number of options and see if it’s right for them as an individual. So, age is a consideration, but frailty will always be the more important.  

Katherine Banwell:

Dr. Rossi, we discussed the process of accessing CAR T-cell therapy, which can be a big undertaking. How do you counsel patients who are considering this treatment option? 

Dr. Adriana Rossi:

Mostly, I want to make sure that they are well-educated and understand as much as we do and as much as we can convey. I am fortunate to be part of a big multidisciplinary team so there is social workers, clinical coordinators, other specialists, dentists, cardiologists, to give all of the perspectives. I like to make sure that they know what it is and also that they know what it isn’t. So, it is not a stem cell transplant and it is not another line of therapy that you just sign up for and go into blindly.  

So, making sure they’ve had all of their questions answered, and it’s not something they read on the Internet. They have spoken with one of the CAR T physicians, understand all of the steps of the process, and have questions to their very individual needs addressed.   

Katherine Banwell:

If a patient is interested in possibly doing CAR T-cell therapy, what questions should they ask their healthcare team?  

Dr. Adriana Rossi:

I think again making it personal to them. Does the team think they are a good candidate? Is this the right time? Because they may be a good candidate but not even need it at the moment. Or, again, there are things that we could do between now and the cells to optimize the success both in efficacy and toxicity.  

Understanding what side effects are expected for that individual because, again, we can usually judge these will be more likely or less likely. And then, do I have a plan in place to find the right center and continue the care and the monitoring near home after that?   

Katherine Banwell:

What are the alternatives if a patient decides CAR T is not right for them?  

Dr. Adriana Rossi:

I would say as part of this newest revolution and fairly comparable in novelty and method of action would be the bispecific antibodies. So, these are molecules.  

They are not cells. And they activate the patient’s own T cells and bring the T cells to the myeloma, causing very similar side effect profile and very similar effectiveness. The rates are a little bit lower but they are administered as mostly a subcutaneous injection that has to be dosed weekly or every other week. The contrast is it’s a continuous therapy, but it does allow us to adjust as we go, which the cellular therapy doesn’t.  

Katherine Banwell:

While there are approved CAR T-cell therapies for myeloma currently, there are also many others that are in clinical trials. Would you talk about some of the ongoing research in this area?  

Dr. Adriana Rossi:

Absolutely. Again, while we celebrate the tremendous changes that these two CAR Ts have made to the field, they are both autologous, meaning we use the patient’s own T cells for manufacturing. They both target BCMA. And they are both what we call second generation T cells. So, other areas are to change the target. So, instead of just targeting BCMA, there are studies specifically targeting GPRC5D, which are coming down fairly soon. Rather than using the patient’s own T cells there are a number of products that use a healthy donor’s T cells, which are available immediately.  

So, we don’t need to go through the bridging therapy, and we don’t have to wait for the cells to be ready. And lastly, there are different manufacturing processes. As I mentioned, the ones we currently have may take up to eight weeks for manufacturing. There are some studies now where cells are basically manufactured, engineered, in 48 hours –  

Katherine Banwell:

Oh, wow.  

Dr. Adriana Rossi:

– and are ready to be infused so that they actually grow in the patient rather than in a Petri dish. So, lots of areas of exploration and I look forward to, in five years, being able to look back and see again how the field has changed.  

Katherine Banwell:

And I’m sure it will, by the sounds of it. Are there any trials introducing CAR T-cell therapy as an earlier line of myeloma treatment?  

Dr. Adriana Rossi:

There are. So, both the products that are now commercially available for the fourth line are being studied in earlier and earlier lines. We actually just this year got results of the CARTITUDE-4 study, which was in one to three prior lines, and expect that that will lead to an earlier approval in the very near future.  

And we have a number of studies, again, with both products looking at patients who have either high risk disease or don’t respond as well as we would like to their frontline therapy, and actually being used as part of that first line.  

Katherine Banwell:

Dr. Rossi, what advice do you have for patients who may be hesitant to participate in a clinical trial?  

Dr. Adriana Rossi:

Education. More than anything, understand what they are. Clinical trials come in all shapes and sizes. We have these exciting molecules that have to go into a first human at some point but we also have tried and true therapies that we know – for example, the CAR T – that is approved in these later lines. That same product is being now offered earlier. So, that has to be within a clinical trial because it’s not the approved indication.  

But it is a product that we know to be safe. We know that it works in advanced disease and are actually expecting that it will work even better in earlier lines. So, clinical trials is a very broad term. Understanding what the patient may be eligible for – meaning, what the study’s looking for – and then comparing that to what the patient is looking for. So, sometimes it’s even modes of therapy. So, if you’re specifically looking for an oral agent, there may be studies that don’t require injections or that many visits. So, really looking widely, speaking to your healthcare physician, and understanding what the options are.   

Katherine Banwell:

And if a patient is interested in possibly participating in a clinical trial, what sorts of questions should they ask?   

Dr. Adriana Rossi:

Very, very good question. First, understanding what clinical trial. Each center will have their own combination. Some studies are available in multiple locations. Some studies are very institution specific. So, meeting with the research team and understanding what are the required testings, what is the required treatments, and what is the required follow-up, I think, is the first part.  

Clinical trials, in order for them to give us the power to generalize and learn lessons are very strict in trying to keep to the schedule just as specified and everything is much more contained. So, making sure that they again understand what they’re signing up for and what they’ll get out of it.  

Katherine Banwell:

What other myeloma research are you excited about?  

Dr. Adriana Rossi:

Well, my focus is in CAR T and so I think, with bias, that is the most exciting part. But I did mention bispecifics. One of the things we need to concede is CAR T really requires you be at a cellular therapy center.  

Whereas, with the bispecifics, while for now experience is still building, the idea is that this is something that could be administered in any practice across the nation. So, being able to reach more patients and those also with different targets, different schedules, different combinations, was another very interesting field as well.   

Katherine Banwell:

As we close out this conversation, Dr. Rossi, I would like to get your take on the future of myeloma. What makes you hopeful?  

Dr. Adriana Rossi:

Just looking back, I think. Again, in the 20 years that I’ve been fortunate enough to participate and see the changes, we have gone through, as I mentioned, three of the four revolutions in the field. And the speed with which each step forward then begets three or four more. As I mentioned, in five years I think we’ll look back and say, “Oh, how quaint, what we were doing in 2023.” So, the speed and the number of wins we’re getting and how quickly that’s translating into direct patient experience is really incredible.  

Katherine Banwell:

Yeah. It seems like there’s a lot of progress and hope in the field.  

Dr. Adriana Rossi:

There absolutely is.  

Katherine Banwell:

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

Dr. Adriana Rossi:

Absolutely. It’s been my pleasure.  

Katherine Banwell:

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.   

Monitoring Health After CAR T-Cell Therapy | What to Expect

Monitoring Health After CAR T-Cell Therapy | What to Expect from Patient Empowerment Network on Vimeo.

When does immune system function return to normal following CAR T-cell therapy? Dr. Adriana Rossi discusses how patients are monitored after the process, the expected recovery time for blood counts, and the importance of communication with your healthcare team at all times.

Dr. Adriana Rossi is co-director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.

See More From Thrive CAR T-Cell Therapy

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Questions to Ask Your Doctor About CAR T-Cell Therapy

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The Value of Myeloma Support Groups and How to Join

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

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

Transcript:

Katherine Banwell:

Is there a typical timeframe for the immune system function to return?  

Dr. Adriana Rossi:

I would say a year is a good time but it’s a very unpredictable wave. So again, unlike stem cell transplant where you have a clear time where the cells are low, they recover, they stay recovered, we have noticed for some patients, they may have low blood counts just during the first month and then be recovered. Some will have no problems in the first month and it’s in the weeks to follow that suddenly either the reds, or the platelets, or the white count may need support.  

And in very rare instances, out to a year, they’re still needing support, sometimes say a growth factor injection once a week.  

Katherine Banwell:

So, how is it monitored over time?  

Dr. Adriana Rossi:

We monitor all those different levels of the immune system. So, we check on the CBC, which is the very common blood counts. We also look at what is called a lymph panel to look at the different types of T cells and make sure that they are recovering. Those usually take about three to six months to recover. The white count, again usually by Day 30, but there are some cases of delayed recovery. And the immunoglobulins, which is the antibody level, we also monitor monthly.  

Katherine Banwell:

What other side effects should patients who are considering CAR T-cell therapy be aware of?  

Dr. Adriana Rossi:

Really, those are the big three. I would say others are very rare but the low blood counts is the one that lasts beyond the time in the hospital. And the rare neurotoxicities that are delayed.  

Katherine Banwell:

When should patients mention any issues they’re experiencing to their healthcare team?  

Dr. Adriana Rossi:

Always. That is a very, very, short answer. Please don’t ever think you are bothering the doctor. I hear that a lot. “Oh, I didn’t want to bother you.” It is never a bother. This is why we are here. So, anything that is happening that is out of the ordinary, please let your healthcare provider know. If it is not something that needs our attention or we don’t need to worry about, we will tell you.  

Katherine Banwell:

Better safe than sorry.   

Dr. Adriana Rossi:

Always.  

Katherine Banwell:

And how does a care partner factor into the process? It seems having a good support system is essential.  

Dr. Adriana Rossi:

It absolutely is. I think the entire journey of myeloma really is what I would consider a team sport. It is not something we go through alone. And the more members of the team you have the better. So, as your medical team, we always value the caregivers. For CAR T specifically, since there is this concern for infections and neurotoxicity, caregivers are really essential.  

They should be well informed, know what to look for, and be the ones to reach out to us if anything is concerning. Again, any symptoms out of the ordinary, any fever, and really be a part of communicating with the medical team.   

Katherine Banwell:

Is there a period where patients are considered out of the woods from CAR T side effects?   

Dr. Adriana Rossi:

Hard to say. Again, I like to emphasize that most patients by Day 30 or 60 are back to work, are feeling themselves, are recovered. Another contrast to stem cell transplants. It’s a much faster recovery. I have patients who within 30 days are eager to go back to work and don’t know what I was talking about or why I insist on seeing them so much.  

But some patients, again, out to a year, may still be requiring visits for support in either the IVIG for the immunoglobins, growth factor support for their counts. So, there are outliers at both extremes. We follow the model of 100 days for recovery.   

Katherine Banwell:

Do some patient types do better than others?  

Dr. Adriana Rossi:

Well, always yes. And we are still endeavoring to figure out who they are and why that is. There are things that we don’t know, can’t predict. But things that we do recognize are again bringing patients whose myeloma is under good control.  

So, instead of having a lot of disease or disease that is in a growth phase, we try to use the bridging therapy to optimize the patient, not only to improve the response, but also minimize the toxicities. 

Katherine Banwell:

Does age have an impact at all?  

Dr. Adriana Rossi:

Not as much. We actually have just finished an 88-year-old patient whose hospital course was remarkably unremarkable, as we would like. I think another difference from stem cells, it is not as rigorous. While each patient, I think, should be part of that decision and that conversation, reviewing what is now a growing number of options and see if it’s right for them as an individual. So, age is a consideration, but frailty will always be the more important.   

Understanding Possible Side Effects of CAR T-Cell Therapy

Understanding Possible Side Effects of CAR T-Cell Therapy from Patient Empowerment Network on Vimeo.

What side effects should you be aware of when considering CAR T-cell therapy? Dr. Adriana reviews the issues that may occur after undergoing CAR T-cell therapy and how the side effects are managed.

Dr. Adriana Rossi is co-director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.

See More From Thrive CAR T-Cell Therapy

Related Resources:

Monitoring Health After CAR T-Cell Therapy | What to Expect

Monitoring Health After CAR T-Cell Therapy | What to Expect

What You Need to Know About Accessing CAR T-Cell Therapy

What You Need to Know About Accessing CAR T-Cell Therapy

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

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

Transcript:

Katherine Banwell:

Of course, we know that CAR T-cell therapy comes with some potential side effects. Let’s talk about some of those side effects and how they’re managed. You mentioned cytokine release syndrome earlier. Let’s start with that. What is it, exactly?  

 Dr. Adriana Rossi:

As I mentioned, cytokines are molecules that the cells of the immune system use to communicate with each other. With this therapy, we are asking the T cells that have been infused to expand, meaning make multiple copies of themselves, and sweep through the body looking for myeloma and basically picking a fight with them.  

So, CRS is what happens when the T cells are too good at their job and they overachieve and then picking a little fight kind of make a big ruckus. The result is what we call inflammation, which the patient will experience usually as a fever.  

But if it does not go – if it continues to go unchecked, that fever can be accompanied by low blood pressure because of these inflammatory markers, difficulty breathing or low oxygen levels. And all of these things are now vastly prevented. CRS is usually treated very quickly and doesn’t get to these higher grades, more complicated fields.  

Katherine Banwell:

How is CRS managed?  

Dr. Adriana Rossi:

We have a couple of very good antidotes. CRS by itself is not just a fever. Certainly, a fever in any patient who is undergoing these kinds of therapies, we will try to rule out any infections. But there are markers in the blood that we can follow. When the blood markers and the fever occur at the same time, we know that cytokines are driving that effect. If it seems to be driven by something we call IL-6, we use tocilizumab (Actemra). If it seems to be driven by IL-1, we use anakinra (Kineret). These are all drugs that are themselves monoclonal antibodies which then will shut down that overreaction and cool things down.  

Katherine Banwell:

Another possible side effect is neurotoxicity. Would you define that term for us?  

Dr. Adriana Rossi:

Yes. That one is harder to define because neurotoxicity in itself is very broad. We usually think of something called ICANS, which is the neurotoxicity associated with the effector cells. That specific neurotoxicity tends to happen in conjunction with CRS.  

And while CRS probably occurs in about 85 percent of patients, the ICANS is usually in the order of 5 percent. So, much, much more rare. And the antidote for that, which most patients know, love, and hate, is steroids.  

Katherine Banwell:

Ah, yes.  

Dr. Adriana Rossi:

I should mention there are other parts of neurotoxicity which I think the most concerning is something that has been known as Parkinsonian symptoms. It’s really just movement disorder. These are exceedingly rare and so we haven’t had a chance to learn very much because there are so few patients who have had this complication. We have learned from the first six patients who had this how to avoid it. And so, I think it’s now even more rare and it really goes into patient selection, to making sure, as I mentioned, that the myeloma isn’t growing very much.  

We monitor to see if the T cells grow too fast, if the CRS is of a high level. These are all predictors of delayed neurotoxicity.  

Katherine Banwell:

What are the signs of neurotoxicity in a patient?  

Dr. Adriana Rossi:

Very specifically, for the ICANS, we have tool called the ICE tool, which is a series of questions to test memory and attention and ability to write and understand and speak. So, most commonly, it would be an inability to speak properly or, if someone is writing a sentence, it’s really a very classic finding. It is no longer spread across the page.  

These are not subtle findings. Part of, again, being in the hospital is to allow us to have this tool twice a day and look for these signs very early on, interfere with their development by giving the patients steroids – usually for a day or two – and resolving it.  

Katherine Banwell:

And is there a potential for long-term issues associated with neurotoxicity?  

Dr. Adriana Rossi:

Certainly, there is always the potential. But the vast majority – again, the ICANS tend to be self-limited while the patient’s in the hospital, and that is why we’re watching during that window. The delayed neurotoxicities, in addition to these very rare movement disorders, we do see some cranial nerve palsies. The seventh cranial nerve, usually recognized as Bell’s palsy, has happened a few times. We really don’t understand the mechanism of what is driving it. It’s inflammation but why there, why that way. So, we tend to use acyclovir, which is the classic treatment for Bell’s palsy and steroids.  

Katherine Banwell:

Dr. Rossi, a suppressed immune system is something that a patient undergoing CAR T-cell therapy should consider. What does it mean, and what precautions should patients take?  

Dr. Adriana Rossi:

That is such a good question, and it is specifically true for patients who are receiving therapies that target BCMA, which both commercial CAR Ts at the moment target.  

Because it is such an effective therapy at bringing down cells that express BCMA, your immune cells that make antibodies, one of the side effects is the immunoglobulins, which are the antibodies, are all very, very low. So, that is one level of immunosuppression.  

The other is the chemotherapy that we use to quiet the T cells can also lower all the blood counts. So, red blood cells and platelets may be low as well and those are not involved with immunity and can be transfused. So, that is a supportive mechanism. For the immune therapies, we usually use IVIG, which is intravenous immunoglobulins to support the patient until they’re able to make their own.  

We also protect them from viral infections with acyclovir or valacyclovir. Protect them from something called PJP pneumonia, which is a virus that specifically appears when you’re very immunosuppressed. Should their neutrophil count be low, that is another type of white blood cell – make sure they’re protected with antibiotics.   

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

Thrive | Advice for Managing Potential CAR T-Cell Therapy Side Effects from Patient Empowerment Network on Vimeo.

Dr. Adriana Rossi, a myeloma expert and researcher, discusses how CAR T-cell therapy has revolutionized care, the process for undergoing this therapy, common side effects of this treatment, and advice for patients considering this option. Dr. Rossi also shares updates in CAR T-cell therapy research and explains what she’s excited about in myeloma care.

Dr. Adriana Rossi is Co-director of the CAR T and stem cell transplant program at the Center for Excellence for Multiple Myeloma at Mount Sinai Health System in New York City. Learn more about Dr. Rossi.

Download Resource Guide

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

Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

Advice for Myeloma Patients Undergoing CAR T-Cell Therapy 

Questions to Ask Your Doctor About CAR T-Cell Therapy

Questions to Ask Your Doctor About CAR T-Cell Therapy 

Transcript:

Katherine Banwell:

Hello, and welcome. I am your host, Katherine Banwell. Today’s program is part of our Thrive series, where we will discuss what to expect and how to manage side effects of CAR T-cell therapy.  

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. Adriana Rossi. Dr. Rossi, welcome. Would you please introduce yourself?  

Dr. Adriana Rossi:

Thank you so much. I am one of the codirectors of the CAR T program at Mount Sinai in New York City and thrilled to be with you today.  

Katherine Banwell:

Thank you. Since we’ll be discussing the ins and outs of CAR T-cell therapy, I thought we could start with your perspective as a researcher in the field. How has this therapy revolutionized myeloma care?  

Dr. Adriana Rossi:

It absolutely has. And I would say in time we’ve had – this is now our fourth revolution. Stem cell transplants was the first time we actually achieved what we call a complete remission in at least a few patients, making myeloma disappear.  

Then, we had the second revolution with the novel agents. Now, we had drug therapies that were giving us these complete remission still at about a 30 percent rate. And then, the monoclonal antibodies were the most recent revolution. And currently, we are in what we call the T-cell redirection.   

It really has been driven by CAR T-cell therapies and something we call bispecific antibodies, which also use your patient’s T cells to kill the myeloma. We are now seeing absolutely unprecedented response rates, meaning almost everybody is responding. Also, depth of response, which we have really learned over time is a way to translate into long remissions. So, every long, very significant remissions. And the early data in patients who have had many prior lines.  

Katherine Banwell:

So, it is very encouraging news.  

Dr. Adriana Rossi:

It is very encouraging.  

Katherine Banwell:

Let’s start with an overview of CAR T-cell therapy. Could you explain how the treatment works?  

Dr. Adriana Rossi:

Absolutely. So, CAR T specifically is speaking to T cells, which are a normal part of the immune system that have been engineered and modified. So, normal part of the immune system T cells have a lot of checks and balances and are constantly looking for cells that are supposed to be killed. For example, something that has a virus in it.  

When we engineer the CAR T-cells, we modify, one, the target so they are now trained to find the specific target on a tumor cell. And we remove all these checks and balances. So, once that T-cell finds its target, it can kill it without all of the side effects. The way normal T  cells communicate with other members of the immune system are something called cytokines. So, we will touch on that a little later, I think, but we also, again, interfere with that communication by engineering the cells.  

Katherine Banwell:

Which patient type qualifies for CAR T?  

Dr. Adriana Rossi:

In 2023, we currently have two approved commercial CAR T products and we do have a number of them in clinical trials. The two that are commercially approved specifically are targeted for patients who are in their fourth line of therapy, so the myeloma has learned to come back that four times.  

They’ve been exposed to all of the regular drugs, which by four lines most patients will have been at least once. We look for patients whose kidney function is at a safe level to tolerate the therapy. And other than that, it’s really having caregiver support and overall ability to come to a center that specializes in this.  

Katherine Banwell:

What’s the process for accessing the CAR T?  

Dr. Adriana Rossi:

The first important part is remembering they exist and having the referring physician remember to send patients our way. Once patients come to our center, they will meet with coordinators, both the clinic coordinators to make sure we have all of the testing, to make sure the heart is healthy enough, the lungs are healthy enough. There’s no infections brewing.  

Financial coordinators to take care of all of the organizing. If patients are coming from further than 30 minutes, setting them up for a place to stay in the city, transportation aid, all of those things. Once we decide to go ahead and have our collection date set, that sort of starts the actual process. Since most of our patients have had stem cell transplants before, there is that point of comparison. I think one of the most important things to remember is CAR T is not stem cells.  

So, while they’re both the cellular therapies, the patient experience is vastly, vastly different. It starts with a collection, where in stem cells you need several days of injections and maybe several days of collection. T-cell collection is a one-day event. We get what we get and then we are going to manufacture them and we can grow them in a Petri dish. There is no minimum and there is no instigating injections to get them going.  

Once they’re collected, the cells are then sent for manufacturing, which may take from four to eight weeks. During that time, patients usually receive what we call a bridging therapy, which is some kind of therapy to keep the myeloma at bay. Not to get rid of it but to keep it under control so that once the cells are ready the patient is also ready. Going into CAR T with growing myeloma can increase the side effects.  

Katherine Banwell:

Go ahead.  

Dr. Adriana Rossi:

I will give you just the final bit. Once the cells are ready, then we plan to give chemotherapy to get the patient’s T cells to not put up a fight. That’s called lymphodepletion. We infuse the cells and they’re now with us for two weeks in the hospital and usually two weeks after.   

Katherine Banwell:

Okay. So, I was going to ask how long patients are in the hospital for the procedure. So, that explains that. So, it is about two weeks. What signifies that a patient is ready to be released and go home?  

Dr. Adriana Rossi:

The reason patients are in the hospital is a very classic expected toxicity experience. So, they’re in the hospital for us to observe, watch. If it happens, which about 80 percent of the time there will be some toxicity for us to address – one that toxicity has resolved, they’re then okay to go home.  

Katherine Banwell:

Okay. That is great advice. Thank you. Of course, we know that CAR T-cell therapy comes with some potential side effects. Let’s talk about some of those side effects and how they’re managed. You mentioned cytokine release syndrome earlier. Let’s start with that. What is it, exactly?  

Dr. Adriana Rossi:

Yes. As I mentioned, cytokines are molecules that the cells of the immune system use to communicate with each other. With this therapy, we are asking the T cells that have been infused to expand, meaning make multiple copies of themselves, and sweep through the body looking for myeloma and basically picking a fight with them.  

So, CRS is what happens when the T cells are too good at their job and they overachieve and then picking a little fight kind of make a big ruckus. The result is what we call inflammation, which the patient will experience usually as a fever.  

But if it does not go – if it continues to go unchecked, that fever can be accompanied by low blood pressure because of these inflammatory markers, difficulty breathing or low oxygen levels. And all of these things are now vastly prevented. CRS is usually treated very quickly and doesn’t get to these higher grades, more complicated fields.  

Katherine Banwell:

How is CRS managed?  

Dr. Adriana Rossi:

We have a couple of very good antidotes. CRS by itself is not just a fever. Certainly, a fever in any patient who is undergoing these kinds of therapies, we will try to rule out any infections. But there are markers in the blood that we can follow. When the blood markers and the fever occur at the same time, we know that cytokines are driving that effect. If it seems to be driven by something we call IL-6, we use tocilizumab (Actemra). If it seems to be driven by IL-1, we use anakinra (Kineret). These are all drugs that are themselves monoclonal antibodies which then will shut down that overreaction and cool things down.   

Katherine Banwell:

Okay. Another possible side effect is neurotoxicity. Would you define that term for us?  

Dr. Adriana Rossi:

Yes. That one is harder to define because neurotoxicity in itself is very broad. We usually think of something called ICANS, which is the neurotoxicity associated with the effector cells. That specific neurotoxicity tends to happen in conjunction with CRS.  

And while CRS probably occurs in about 85 percent of patients, the ICANS is usually in the order of 5 percent. So, much, much more rare. And the antidote for that, which most patients know, love, and hate, is steroids.  

Katherine Banwell:

Ah, yes.  

Dr. Adriana Rossi:

I should mention there are other parts of neurotoxicity which I think the most concerning is something that has been known as Parkinsonian symptoms. It’s really just movement disorder. These are exceedingly rare and so we haven’t had a chance to learn very much because there are so few patients who have had this complication. We have learned from the first six patients who had this how to avoid it. And so, I think it’s now even more rare and it really goes into patient selection, to making sure, as I mentioned, that the myeloma isn’t growing very much.  

We monitor to see if the T cells grow too fast, if the CRS is of a high level. These are all predictors of delayed neurotoxicity.  

Katherine Banwell:

What are the signs of neurotoxicity in a patient?  

Dr. Adriana Rossi:

Very specifically, for the ICANS, we have tool called the ICE tool, which is a series of questions to test memory and attention and ability to write and understand and speak. So, most commonly, it would be an inability to speak properly or, if someone is writing a sentence, it’s really a very classic finding. It is no longer spread across the page.  

These are not subtle findings. Part of, again, being in the hospital is to allow us to have this tool twice a day and look for these signs very early on, interfere with their development by giving the patients steroids – usually for a day or two – and resolving it.  

Katherine Banwell:

So, that’s how neurotoxicity is managed, then.  

Dr. Adriana Rossi:

Yes.  

Katherine Banwell:

And is there a potential for long-term issues associated with neurotoxicity?  

Dr. Adriana Rossi:

Certainly, there is always the potential. But the vast majority – again, the ICANS tend to be self-limited while the patient’s in the hospital, and that is why we’re watching during that window. The delayed neurotoxicities, in addition to these very rare movement disorders, we do see some cranial nerve palsies. The seventh cranial nerve, usually recognized as Bell’s palsy, has happened a few times. We really don’t understand the mechanism of what is driving it. It’s inflammation but why there, why that way. So, we tend to use acyclovir, which is the classic treatment for Bell’s palsy and steroids.  

Katherine Banwell:

Dr. Rossi, a suppressed immune system is something that a patient undergoing CAR T-cell therapy should consider. What does it mean and what precautions should patients take?  

Dr. Adriana Rossi:

That is such a good question and it is specifically true for patients who are receiving therapies that target BCMA, which both commercial CAR Ts at the moment target.  

Because it is such an effective therapy at bringing down cells that express BCMA, your immune cells that make antibodies, one of the side effects is the immunoglobulins, which are the antibodies, are all very, very low. So, that is one level of immunosuppression.  

The other is the chemotherapy that we use to quiet the T cells can also lower all the blood counts. So, red blood cells and platelets may be low as well and those are not involved with immunity and can be transfused. So, that is a supportive mechanism. For the immune therapies, we usually use IVIG, which is intravenous immunoglobulins to support the patient until they’re able to make their own.  

We also protect them from viral infections with acyclovir or valacyclovir. Protect them from something called PJP pneumonia, which is a virus that specifically appears when you’re very immunosuppressed. Should their neutrophil count be low, that is another type of white blood cell – make sure they’re protected with antibiotics.  

Katherine Banwell:

Is there a typical timeframe for the immune system function to return?  

Dr. Adriana Rossi:

I would say a year is a good time but it’s a very unpredictable wave. So again, unlike stem cell transplant where you have a clear time where the cells are low, they recover, they stay recovered, we have noticed for some patients, they may have low blood counts just during the first month and then be recovered. Some will have no problems in the first month and it’s in the weeks to follow that suddenly either the reds, or the platelets, or the white count may need support.  

And in very rare instances, out to a year, they’re still needing support, sometimes say a growth factor injection once a week.  

Katherine Banwell:

So, how is it monitored over time?  

Dr. Adriana Rossi:

We monitor all those different levels of the immune system. So, we check on the CBC, which is the very common blood counts. We also look at what is called a lymph panel to look at the different types of T cells and make sure that they are recovering. Those usually take about three to six months to recover. The white count, again usually by Day 30, but there are some cases of delayed recovery. And the immunoglobulins, which is the antibody level, we also monitor monthly.  

Katherine Banwell:

What other side effects should patients who are considering CAR T-cell therapy be aware of?  

Dr. Adriana Rossi:

Really, those are the big three. I would say others are very rare but the low blood counts is the one that lasts beyond the time in the hospital. And the rare neurotoxicities that are delayed.  

Katherine Banwell:

When should patients mention any issues they’re experiencing to their healthcare team?  

Dr. Adriana Rossi:

Always. That is a very, very, short answer. Please don’t ever think you are bothering the doctor. I hear that a lot. “Oh, I didn’t want to bother you.” It is never a bother. This is why we are here. So, anything that is happening that is out of the ordinary, please let your healthcare provider know. If it is not something that needs our attention or we don’t need to worry about, we will tell you.  

Katherine Banwell:

Better safe than sorry.  

Dr. Adriana Rossi:

Always.  

Katherine Banwell:

And how does a care partner factor into the process? It seems having a good support system is essential.  

Dr. Adriana Rossi:

It absolutely is. I think the entire journey of myeloma really is what I would consider a team sport. It is not something we go through alone. And the more members of the team you have the better. So, as your medical team, we always value the caregivers. For CAR T specifically, since there is this concern for infections and neurotoxicity, caregivers are really essential. They should be well informed, know what to look for, and be the ones to reach out to us if anything is concerning. Again, any symptoms out of the ordinary, any fever, and really be a part of communicating with the medical team.  

Katherine Banwell:

Is there a period where patients are considered out of the woods from CAR T side effects?   

Dr. Adriana Rossi:

Hard to say. Again, I like to emphasize that most patients by Day 30 or 60 are back to work, are feeling themselves, are recovered. Another contrast to stem cell transplants. It’s a much faster recovery. I have patients who within 30 days are eager to go back to work and don’t know what I was talking about or why I insist on seeing them so much.  

But some patients, again, out to a year, may still be requiring visits for support in either the IVIG for the immunoglobins, growth factor support for their counts. So, there are outliers at both extremes. We follow the model of 100 days for recovery.  

Katherine Banwell:

Do some patient types do better than others?  

Dr. Adriana Rossi:

Well, always yes. And we are still endeavoring to figure out who they are and why that is. There are things that we don’t know, can’t predict. But things that we do recognize are again bringing patients whose myeloma is under good control.  

So, instead of having a lot of disease or disease that is in a growth phase, we try to use the bridging therapy to optimize the patient, not only to improve the response, but also minimize the toxicities. 

Katherine Banwell:

Does age have an impact at all?  

Dr. Adriana Rossi:

Not as much. We actually have just finished an 88-year-old patient whose hospital course was remarkably unremarkable, as we would like. I think another difference from stem cells, it is not as rigorous. While each patient, I think, should be part of that decision and that conversation, reviewing what is now a growing number of options and see if it’s right for them as an individual. So, age is a consideration, but frailty will always be the more important.  

Katherine Banwell:

Dr. Rossi, we discussed the process of accessing CAR T-cell therapy, which can be a big undertaking. How do you counsel patients who are considering this treatment option? 

Dr. Adriana Rossi:

Mostly, I want to make sure that they are well-educated and understand as much as we do and as much as we can convey. I am fortunate to be part of a big multidisciplinary team so there is social workers, clinical coordinators, other specialists, dentists, cardiologists, to give all of the perspectives. I like to make sure that they know what it is and also that they know what it isn’t. So, it is not a stem cell transplant and it is not another line of therapy that you just sign up for and go into blindly.  

So, making sure they’ve had all of their questions answered, and it’s not something they read on the Internet. They have spoken with one of the CAR T physicians, understand all of the steps of the process, and have questions to their very individual needs addressed.   

Katherine Banwell:

If a patient is interested in possibly doing CAR T-cell therapy, what questions should they ask their healthcare team?  

Dr. Adriana Rossi:

I think again making it personal to them. Does the team think they are a good candidate? Is this the right time? Because they may be a good candidate but not even need it at the moment. Or, again, there are things that we could do between now and the cells to optimize the success both in efficacy and toxicity.  

Understanding what side effects are expected for that individual because, again, we can usually judge these will be more likely or less likely. And then, do I have a plan in place to find the right center and continue the care and the monitoring near home after that?   

Katherine Banwell:

What are the alternatives if a patient decides CAR T is not right for them?  

Dr. Adriana Rossi:

I would say as part of this newest revolution and fairly comparable in novelty and method of action would be the bispecific antibodies. So, these are molecules.  

They are not cells. And they activate the patient’s own T cells and bring the T cells to the myeloma, causing very similar side effect profile and very similar effectiveness. The rates are a little bit lower but they are administered as mostly a subcutaneous injection that has to be dosed weekly or every other week. The contrast is it’s a continuous therapy, but it does allow us to adjust as we go, which the cellular therapy doesn’t.  

Katherine Banwell:

While there are approved CAR T-cell therapies for myeloma currently, there are also many others that are in clinical trials. Would you talk about some of the ongoing research in this area?  

Dr. Adriana Rossi:

Absolutely. Again, while we celebrate the tremendous changes that these two CAR Ts have made to the field, they are both autologous, meaning we use the patient’s own T cells for manufacturing. They both target BCMA. And they are both what we call second generation T cells. So, other areas are to change the target. So, instead of just targeting BCMA, there are studies specifically targeting GPRC5D, which are coming down fairly soon. Rather than using the patient’s own T cells there are a number of products that use a healthy donor’s T cells, which are available immediately.  

So, we don’t need to go through the bridging therapy, and we don’t have to wait for the cells to be ready. And lastly, there are different manufacturing processes. As I mentioned, the ones we currently have may take up to eight weeks for manufacturing. There are some studies now where cells are basically manufactured, engineered, in 48 hours –  

Katherine Banwell:

Oh, wow.  

Dr. Adriana Rossi:

– and are ready to be infused so that they actually grow in the patient rather than in a Petri dish. So, lots of areas of exploration and I look forward to, in five years, being able to look back and see again how the field has changed.  

Katherine Banwell:

And I’m sure it will, by the sounds of it. Are there any trials introducing CAR T-cell therapy as an earlier line of myeloma treatment?  

Dr. Adriana Rossi:

There are. So, both the products that are now commercially available for the fourth line are being studied in earlier and earlier lines. We actually just this year got results of the CARTITUDE-4 study, which was in one to three prior lines, and expect that that will lead to an earlier approval in the very near future.  

And we have a number of studies, again, with both products looking at patients who have either high risk disease or don’t respond as well as we would like to their frontline therapy, and actually being used as part of that first line.  

Katherine Banwell:

Dr. Rossi, what advice do you have for patients who may be hesitant to participate in a clinical trial?  

Dr. Adriana Rossi:

Education. More than anything, understand what they are. Clinical trials come in all shapes and sizes. We have these exciting molecules that have to go into a first human at some point but we also have tried and true therapies that we know – for example, the CAR T – that is approved in these later lines. That same product is being now offered earlier. So, that has to be within a clinical trial because it’s not the approved indication.  

But it is a product that we know to be safe. We know that it works in advanced disease and are actually expecting that it will work even better in earlier lines. So, clinical trials is a very broad term. Understanding what the patient may be eligible for – meaning, what the study’s looking for – and then comparing that to what the patient is looking for. So, sometimes it’s even modes of therapy. So, if you’re specifically looking for an oral agent, there may be studies that don’t require injections or that many visits. So, really looking widely, speaking to your healthcare physician, and understanding what the options are.   

Katherine Banwell:

And if a patient is interested in possibly participating in a clinical trial, what sorts of questions should they ask?   

Dr. Adriana Rossi:

Very, very good question. First, understanding what clinical trial. Each center will have their own combination. Some studies are available in multiple locations. Some studies are very institution specific. So, meeting with the research team and understanding what are the required testings, what is the required treatments, and what is the required follow-up, I think, is the first part.  

Clinical trials, in order for them to give us the power to generalize and learn lessons are very strict in trying to keep to the schedule just as specified and everything is much more contained. So, making sure that they again understand what they’re signing up for and what they’ll get out of it.  

Katherine Banwell:

What other myeloma research are you excited about?  

Dr. Adriana Rossi:

Well, my focus is in CAR T and so I think, with bias, that is the most exciting part. But I did mention bispecifics. One of the things we need to concede is CAR T really requires you be at a cellular therapy center.  

Whereas, with the bispecifics, while for now experience is still building, the idea is that this is something that could be administered in any practice across the nation. So, being able to reach more patients and those also with different targets, different schedules, different combinations, was another very interesting field as well.   

Katherine Banwell:

As we close out this conversation, Dr. Rossi, I would like to get your take on the future of myeloma. What makes you hopeful?  

Dr. Adriana Rossi:

Just looking back, I think. Again, in the 20 years that I’ve been fortunate enough to participate and see the changes, we have gone through, as I mentioned, three of the four revolutions in the field. And the speed with which each step forward then begets three or four more. As I mentioned, in five years I think we’ll look back and say, “Oh, how quaint, what we were doing in 2023.” So, the speed and the number of wins we’re getting and how quickly that’s translating into direct patient experience is really incredible.  

Katherine Banwell:

Yeah. It seems like there’s a lot of progress and hope in the field.  

Dr. Adriana Rossi:

There absolutely is.  

Katherine Banwell:

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

Dr. Adriana Rossi:

Absolutely. It’s been my pleasure.  

Katherine Banwell:

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.   

Can Bone Marrow Return to Normal After CLL Treatment?

Can Bone Marrow Return to Normal After CLL Treatment? from Patient Empowerment Network on Vimeo.

Is it possible for chronic lymphocytic leukemia (CLL) patients to achieve normal bone marrow after CLL treatment? Expert Dr. Ryan Jacobs explains MRD-undetectable status and the typical time period to deep CLL remission.

Dr. Ryan Jacobs is a hematologist/oncologist specializing in chronic lymphocytic leukemia from Levine Cancer Institute. Learn more about Dr. Jacobs.

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Should CLL Patients Worry About Enlarged Lymph Nodes?


Transcript:

Lisa Hatfield:

This patient is asking, upon completion of venetoclax (Venclexta) and obinutuzumab (Gazyva) and achieving MRD-undetectable status, how long does it take your bone marrow to achieve improved hemoglobin, hematocrit platelets, white blood cells? And does it always return to normal? And I might add in there just any kind of treatment, does the bone marrow typically return to “normal”? And how long does that take?

Dr. Jacobs:

So the majority of patients treated in the first-line setting and actually in the relapse setting with a combination of venetoclax and obinutuzumab, will have their CLL go into such a deep remission that we cannot detect it in 1 out of 10,000 cancer cells. So that is called MRD-undetectable. Those patients are usually also in complete remission, which means if you look at the bone marrow, you’re not going to see any CLL there. So the majority of patients have their counts normalized while they’re still on the venetoclax. You take it for a year. The complete remission is usually achieved before therapy is completed. And what little, if any CLL is in the bone marrow is not causing a drop in the counts. Now, of course, patients can have the toxicity-reduced counts. And if that’s the case, if it’s a toxicity issue, then it should resolve when you stop treatment. So I would say, usually it does return to normal, if not all…when they’re on therapy, then after therapy. If it’s a relapsed patient that’s seen a lot of therapies though, the bone marrow might never return to normal. 

Lisa Hatfield:

How far out are we from curative therapies for CLL patients with the tougher prognostic indicators?

Dr. Jacobs:

So I think curative is an interesting question, and it can mean different things to different people. But we’ve already shown at the most recent American Society of Hematology meeting, when they looked at the average life expectancy of patients without CLL, since the time that ibrutinib (Imbruvica) got approved and then now CLL patients, the survival curves are overlapping. So as of now, it looks like with our newer treatments that a CLL patient should reasonably expect to live a normal life expectancy. Does that mean cure? Well, if by cure you mean, does the disease go away forever with one treatment? We still don’t think we have that therapy for most patients. But we’ll see as we get longer and longer follow-up with some of these newer agents is there are going to be a proportion of patients that never relapse, that ibrutinib is going to have the longest follow up because it was the first one. I was just looking at a poster at the European Hematology Association meeting where they’ve followed patients seven, eight years out and more than half have still not progressed that got ibrutinib as a first-line therapy. So it’s reasonable to think that maybe some will never progress.


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What Tests Are Essential to Understand a Myeloma Diagnosis?

What Tests Are Essential to Understand a Myeloma Diagnosis? from Patient Empowerment Network on Vimeo.

Myeloma diagnoses can vary greatly, so it’s important to understand an individual’s disease before choosing a treatment approach. Dr. Francesca Cottini outlines the tests to better understand myeloma and explains the purpose of in-depth cytogenetic testing.
 
Dr. Francesca Cottini is Assistant Professor in the Division of Hematology at the Ohio State University Comprehensive Cancer Center. Learn more about Dr. Cottini.

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Transcript:

Katherine:

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. 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.  

How Can You Thrive With an MPN? Advice for Navigating Care.

How Can You Thrive With an MPN? Advice for Navigating Care. from Patient Empowerment Network on Vimeo.

How can you thrive with an MPN? In this animated explainer video, an MPN specialist and myelofibrosis patient discuss how to make informed decisions about your care and live a full life with an MPN.

 

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How Can Patients Navigate Care and Thrive with an MPN?


Transcript:

Brian: 

Hi, I’m Brian. Nice to meet you! Many years ago, I was diagnosed with a condition called myelofibrosis. At first, it was a scary to learn that I had cancer, but once I found the right treatment option for me, I’ve been living a full life.  

Meet, Dr. Liu – my doctor. 

Dr. Liu: 

Hi! I’m Dr. Liu, and I’m a hematologist specializing in the care of people with myeloproliferative neoplasms or MPNs.   

MPNs are a group of blood cancers that are characterized by the bone marrow overproducing a certain type of cell. The three types of MPNs are essential thrombocythemia, or ET,  polycythemia vera or PV, and myelofibrosis, or MF. 

As Brian mentioned, with the right treatment, it is possible to live a full life and to thrive with an MPN. 

Brian: 

It’s so true. Navigating my care has been much easier because I partner with my healthcare team – participating in decisions makes me feel like an important member of the team. 

Dr. Liu: 

That’s right, Brian. When considering treatment, it’s important to weigh all of your options.  

While your healthcare team is the expert when it comes to the clinical side of your disease, you as the patient, are the expert on how treatment will impact YOU and your lifestyle.  

Brian: 

And as someone who knows my needs well, my wife is another key member of my team.  She comes with me to appointments and takes notes during visits, and when it is time to make decisions about my care, we both feel well-informed about the options. 

So, Dr. Liu – what factors should be considered when choosing an MPN treatment?  

Dr. Liu: 

Well, it’s important to note that everyone’s MPN is different so what may work for one person, may not work for another. In general, we consider certain factors,1 such as: 

  • The type of MPN, whether it is ET, PV, or MF. 
  • The patient’s age and overall health. 
  • Test results, including blood work or any genetic testing that has taken place. 
  • The symptom burden, which basically means how much the disease symptoms are interfering with a patient’s quality of life. 
  • Any pre-existing health issues. 
  • Finally, and most importantly, the patient’s preference.  

Brian: 

And I like to make informed decisions. So, when considering therapy, I also did some research on my own, and then discussed the information with my healthcare team. It helped my wife and me understand what we’d learned, and confirmed our decision. 

Dr. Liu, what sort of questions should patients ask their doctor when considering a treatment plan? 

Dr. Liu: 

Great question. When choosing therapy, patients should ask: 

  • How is the treatment administered, and how often will I need treatment? 
  • What are the potential side effects of the treatment? 
  • How will the effectiveness of the treatment be monitored? 
  • And, what are options if this treatment doesn’t work for me? 

Brian: 

That’s great advice. Once you’ve begun treatment, it’s important to continue to share how you are feeling with your healthcare team – be sure to mention any side effects or symptoms you may be having with your team. 

Dr. Liu: 

That’s right, Brian. If you speak up about what’s bothering you, we can usually find a way to manage the issue. 

It’s also important point to tell your doctor if you’ve missed a dose of your medication. Many of the newer MPN therapies are self-administered, and it’s important to let us know so we can adjust the plan if necessary. 

So, what steps should you take to thrive in your life with an MPN? 

Brian: 

  • First, understand and participate in treatment decisions. Be sure to share your personal preferences. 
  • Then, communicate regularly with your healthcare team – don’t wait to share information only when you have an appointment.  
  • And, utilize your whole team – nurses, nurse practitioners, and others, are all there to help you. 
  • Use your patient portal. You can view lab work and test results, or even use the messaging feature to communicate with your team. 
  • Bring a friend or loved one to appointments and always write down any questions or concerns in advance.  

Dr. Liu: 

And, most importantly, remember you are at the center of your care. Advocate for yourself! 

To learn more, visit powerfulpatients.org/MPN to access a library of tools. Thanks for joining us! 

What Are Indicators of MPN Progression?

What Are Indicators of MPN Progression?  from Patient Empowerment Network on Vimeo.

What are signs that essential thrombocythemia (ET), polycythemia vera (PV) or myelofibrosis (MF) may be progressing? Dr. Jeanne Palmer, of the Mayo Clinic in Arizona, reviews factors that may indicate progression and discusses how blood counts are used in disease monitoring.

Dr. Jeanne Palmer is a hematologist specializing in myeloproliferative neoplasms (MPNs) and bone marrow transplant at the Mayo Clinic in Arizona. Dr. Palmer also serves as Director of the Blood and Marrow Transplant Program and is Vice Chair and Section Chief for Hematology. Learn more about Dr. Palmer, here.

 

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Transcript:

Katherine Banwell:

Okay. Katie had this question. “What are the signs of progression from PV to MF or AML, both clinically and in blood tests, and when do you need a new bone marrow biopsy to check for this happening?” 

Dr. Jeanne Palmer:

So, in terms of progression, there are several things that we see happen. 

I think most importantly is, let’s say you have PV, and you’ve always been on medication, and it’s been hard to control. And all of a sudden, you don’t need medication to control it anymore, or the same thing for essential thrombocythemia. You have been taking medication, and all of a sudden your platelets go down, and you don’t need to take drugs anymore. A lot of times people are like, “Oh, that means I’m fixed and I’m well,” not necessarily, you really need to make sure to talk to your healthcare provider and potentially get a bone marrow biopsy. 

Now, the other thing – sometimes the blood counts will actually drop too low, so you’ll have somebody who has PV, who has always been too high and then all of the sudden they come in, and their hemoglobin is very low, and they’re anemic, and that’s another situation where you do that. So, anytime the blood counts start to drop is concerning. 

Now, it’s a continuum, so the blood counts may drop as you’re at the point of transitioning but it doesn’t – it’s not like if your blood count is dropping you say, “Oh my God, I have myelofibrosis, I need a bone marrow transplant tomorrow.” That’s not necessarily the case. This is generally a transition type process. 

Also when the spleen starts to get enlarged. Now, the spleen can be enlarged even in the setting of just ET or just PV, so spleen enlargement does not necessarily mean you’re transforming, but it can be one of the things that we would see that would indicate that. 

Katherine Banwell:

Okay. 

Dr. Jeanne Palmer:

And then finally white blood cell count increasing can often be a sign of that. Now, in terms of progression to AML, that is generally something we’ll see in the blood. AML or acute myeloid leukemia, is indicated by the presence of blasts at greater than 20 percent. Now, many patients with myelofibrosis, in particular, but even PV and ET, may have blasts in their peripheral blood. Blasts are normal. If I did a marrow on every healthy person out there, they are going to have some blasts, because these are the first part of the development of white blood cells. So, they’re like baby white blood cells. But what the problem is, is when they start to grow too much. 

And so in the setting of myelofibrosis and even sometimes with these other diseases, the blasts will be in the peripheral blood primarily because the bone marrow is damaged and doesn’t hold them in very well. It becomes AML when it gets greater than 20 percent, so that blasts of greater than 20 percent in the peripheral blood or in the bone marrow but a lot of times we find it in the peripheral blood is where we indicate this has progressed to AML. 

Katherine Banwell:

Yeah.  

Dr. Jeanne Palmer:

Blasts of greater than 10 percent are also something that we really want to pay attention to, because that would suggest that the disease is starting to become more aggressive. Now, blasts vary, so for example, I’ve had patients go up to 11 and then drop back down to 3 or 4, and then they say around 3 or 4 or 5. So, you always want to make sure to double-check because one blast count at 11 percent, whereas it’s very important to address, may not necessarily reflect that you need to change in treatment at that time. Again, these blood tests, I always tell people, do not freak out over one blood test. 

Make sure you get at least a couple of them to really confirm what you are looking at. 

How to Make an Informed MPN Treatment Decision

How to Make an Informed MPN Treatment Decision from Patient Empowerment Network on Vimeo.

When faced with several options, how can you decide on the best therapy for your essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF)? In this explainer video, Katrina and her doctor walk through important considerations when choosing treatment and provide advice for partnering with your healthcare team.

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Transcript:

Katrina:

Hi, I’m Katrina. Nice to meet you!

Several years ago, I started having headaches and felt very tired. After a trip to the doctor and undergoing bloodwork, I was diagnosed with polycythemia vera, or PV, which is a rare blood cancer that causes my body to produce too many blood cells. It was overwhelming at the time to learn that I had a blood cancer, but my hematologist, Dr. Liu, told me more about the condition and how it’s managed.

Here’s Dr. Liu–she can explain it further.

Dr. Liu:

Hi! I’m Dr. Liu, and I’m a hematologist specializing in the care and treatment of people with myeloproliferative neoplasms or MPNs. MPNs are a group of blood cancers that are characterized by the bone marrow overproducing a certain type of cell. Katrina was diagnosed with PV, which is one of the three MPNs. The three types of MPNs are:

Essential thrombocythemia, or ET, which means that the body is producing too many platelets. The second is polycythemia vera or PV. PV is characterized by the overproduction of red blood cells, and, in some cases, elevated white blood cells and platelets. And the third is myelofibrosis or MF, which causes scarring in the bone marrow that disrupts the normal production of blood cells.

When a patient is diagnosed with any of these conditions, there is a chance they could progress from one condition to the next.

Those that have been diagnosed with ET, PV or MF, should have regular visits with their hematologist to monitor their condition and find the most appropriate treatment to manage their MPN.

Katrina:

After I was diagnosed, I met with Dr. Liu and she walked me through the goals of treatment for PV.

Dr. Liu:

Right! First, we talked about the clinical goals of treatment for PV, which are to reduce the risk of a blood clot and ease or eliminate any symptoms.

And, it’s important to note that because each of the MPNs is different, they are treated differently – be sure to discuss the specific goals of YOUR MPN with your doctor.

Katrina and I reviewed the effectiveness of each treatment option, including how treatment would be administered, and took all of her test results into consideration to make sure we found the best, most personalized treatment option for her PV. Then, we went over what our next steps would be if the treatment plan needed to be adjusted.

Katrina:

Next, we talked about another key treatment goal: symptom management. Dr. Liu let me know that I should make her aware of any symptoms that I may be having, even if I don’t think it’s related to my PV.

Dr. Liu:

Exactly, Katrina. A significant change in symptoms can indicate that it may be time to switch treatments or that the disease might be changing. Those symptoms may include enlarged spleen, fever, itching, fatigue and anemia, among others. This is why it’s always important to not only have blood counts checked regularly, but it’s essential to tell your doctor or nurse about any symptoms you may be having, even if you don’t think it’s related to your MPN.

And, last but not least, we discussed the most important treatment goal: Katrina’s goals. Katrina let me know that she’s very social and enjoys playing golf and tennis with her friends – we wanted to make sure she could continue doing the activities she loves.

Katrina:

Dr. Liu reviewed each of the treatment approaches with me, including potential side effects for every therapy and how it could impact my lifestyle. We discussed the pros and cons of each option, together.

Dr. Liu:

Exactly! When deciding on therapy, you and your doctor may also consider:

Your age and overall health, any presence or history of other medical problems, and the financial impact of a treatment plan.

Katrina:

In addition to asking questions, my daughter, Sarah, took notes during our appointments, since it was often hard for me to absorb everything at once.

We also made sure to talk about the appointment on our way home, while the information was fresh on our minds. And we did our part by researching PV and bringing a list of questions to each appointment.

Sarah found an office visit planner on the Patient Empowerment Network website that helped me organize my health info and questions.

Dr. Liu:

As you can see, Katrina and her daughter were actively engaged in each care decision. It’s vital that patients feel empowered to speak up. If you can, bring a friend or loved one along to your appointment.

And, if you are able, it’s a good idea to seek a second opinion or a consultation with an MPN specialist to help you feel confident in your care decisions.

Katrina:

Dr. Liu let me know that she would monitor my condition through regular physical exams, blood work and frequent communication. She made Sarah and I feel included in the decision-making process, as if it were a collaboration.

Dr. Liu:

That’s right. This is a partnership. So, what steps can you take to be more engaged in your MPN care?

  • Bring a friend or loved one to your appointments.
  • Understand and articulate the goals of your treatment plan.
  • Learn about your options and weigh the pros and cons of each approach.
  • Consider a second opinion or a consult with a specialist.

Katrina:

That’s great advice, Dr. Liu. To learn more, visit powerfulpatients.org/MPN to access a library of tools.

Thanks for joining us!

Essential Lab Tests for Myeloproliferative Neoplasm (MPN) Patients

Essential Lab Tests for Myeloproliferative Neoplasm (MPN) Patients from Patient Empowerment Network on Vimeo.

 Lindsey Lyle, a physician assistant specializing in MPNs, reviews the lab tests that should be administered following an MPN diagnosis and how the results could affect overall care.

Lindsey Lyle is a physician assistant at the University of Colorado Cancer Center, specializing in hematological malignancies with a subspecialty in myeloproliferative neoplasms (MPNs). More about this expert here.

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Transcript:

Lindsey:

When somebody is diagnosed with an MPN, there are a variety of tests that are important for coming up with treatment strategies. And so, really, before starting treatment, it’s fairly imperative to have a CBC, or complete blood count, which was very likely done that led to the diagnosis of the MPN, but that’s very critical, as well as having a differential. This is basically just looking a little bit deeper at the white blood cells and their components, so that’s a critical part of the CBC, or complete blood count.

And then, having a chemistry panel, just to look at organ functioning, such as the kidney functioning and the liver functioning, as well as different electrolytes that may be indicative of something going on that would maybe impact treatment.

Additionally, having a bone marrow biopsy with molecular testing is advised. This is very critical in leading to the diagnosis of the MPN and then, also, really differentiating what subtype of MPN a patient may have.

The bone marrow is very critical for this purpose, and the genetic testing helps us to understand perhaps if a patient is having a higher-risk disease or a lower-risk disease and can help guide treatment as well. There are a variety of other chemistry tests that are done that can help specifically when looking at patients with polycythemia vera. This may be called an erythropoietin level.

Additionally, iron studies are generally recommended before starting treatment for MPNs, just to assess iron storage, availability, and that sort of component to the treatment may vary depending on that result. Additionally, if patients are having any sort of symptoms related to an enlarged spleen, generally, having an imaging study may be warranted if the symptom is quite severe and causing problems, and getting a baseline prior to starting treatment is generally a good idea.

When looking at a CBC, there are really three main cell lines that we monitor closely in MPNs regardless of the subtype, and this includes the white blood cell count, the red blood cell count or hemoglobin and hematocrit – those are measures of the total red blood cell count – and then, also, platelets. And so, these really are three different types of cells that your bone marrow produces that help with different functions.

And so, monitoring for any sort of changes within these three cell lines – white blood cells, red blood cells, or platelets – can really help us know maybe how the disease is changing, how a patient is responding to treatment, so these three key laboratory values are very necessary and really help us as providers and U.S. patients monitor progress, or for any changes in a positive way, or perhaps in a way that needs to be addressed.