Advances in Managing CAR T-Cell Therapy Side Effects

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Advances in Managing CAR T-Cell Therapy Side Effects from Patient Empowerment Network on Vimeo.

What progress is being made in treating the side effects of CAR T-cell therapy? Myeloma expert Dr. Krina Patel discusses the research and advances being made in understanding and managing the common issues associated with this treatment.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. 

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CAR T-Cell Therapy for Myeloma | What Are the Advantages

CAR T-Cell Therapy for Myeloma | What Are the Advantages?

 Recovering From CAR T-Cell Therapy | What Can Myeloma Patients Expect

Recovering From CAR T-Cell Therapy | What Can Myeloma Patients Expect?

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

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

Transcript:

Katherine Banwell:

Dr. Patel, what about managing the side effects of CAR T? Is that improving?  

Dr. Krina Patel:

It is. I think just the fact that we are now seeing less of the neurotoxicity that we were seeing in the initial patients that were getting CAR T, and the serious neurotoxicity like the Parkinsonianism or patients couldn’t walk or hold things because of the tremors they were having that were so significant.  

And then something kinda like Guillain-Barré where people are getting ascending paralysis. And so, again, those are very serious things that we don’t want any of our patients to get. And again, most of it was with cilta-cel and their CARTITUDE-1 study. There is a black-box warning with ide-cel too that that can happen.  

We just don’t see it at the same rate. And again, when patients got better bridging going into CAR T, that rate dropped from 6% to 0.5%. So, it really is a huge difference by just giving better bridging and having myeloma controlled better going in.  

We are seeing some other side effects that we didn’t necessarily see on the original clinical trials, like facial palsies. These are things where patients can talk very well anymore or their side of their face is drooping. And those are reversible thankfully, for the most part with steroids, things like that. So, we watch for that. There’s some other side effects.

Again, these are immune cells going into your body, so anything can happen. So, we definitely keep a close eye on all of our patients. But for the most part, especially things like infections and this neurotoxicity, we’ve learned that again the less myeloma going in, the better patients do and the faster they recover.  

So, for the most part, patients now are doing much, much better than when patients were originally on those trials where we didn’t know what was gonna happen. And I think the infection piece is such a big deal; that our patients definitely need supportive care.  

So, even though this is a one-and-done where you get your chemo, you get your CAR T’s and then you’re not on any myeloma therapy, you are on supportive therapies; so, things like IVIG for your immune system, things to protect you against something called PJP pneumonia for at least six months if not longer.  

You’re still on anti-shingles medication. So, it’s not that you stop all medicines, but it’s you stop the myeloma medicines. And then, at least for the first six months, maybe even up to a year we have to make sure you don’t get any major infections.  

CAR T-Cell Therapy for Myeloma | What Are the Advantages?

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CAR T-Cell Therapy for Myeloma | What Are the Advantages? from Patient Empowerment Network on Vimeo.

How has CAR T-cell therapy transformed care for myeloma patients? Myeloma expert and researcher Dr. Beth Faiman shares results from the KarMMa study that compared CAR T-cell therapy versus a standard regimen, and the benefits of this therapy over time.

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.

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Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

 Is CAR T-Cell Therapy Right for You? Questions to Ask Your Myeloma Care Team

Is CAR T-Cell Therapy Right for You? Questions to Ask Your Myeloma Care Team

 Recovering From CAR T-Cell Therapy | What Can Myeloma Patients Expect

Recovering From CAR T-Cell Therapy | What Can Myeloma Patients Expect?

Transcript:

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.   

Recovering From CAR T-Cell Therapy | What Can Myeloma Patients Expect?

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Recovering From CAR T-Cell Therapy | What Can Myeloma Patients Expect? from Patient Empowerment Network on Vimeo.

What can myeloma patients expect after undergoing CAR T-cell therapy? Myeloma expert and researcher Dr. Beth Faiman discusses returning to life after the CAR T process, advice for physical activity, and immune system concerns during recovery.

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.

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

 CAR T-Cell Therapy | Care and Monitoring Post-Treatment

CAR T-Cell Therapy | Care and Monitoring Post-Treatment

Transcript:

Katherine Banwell:

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.  

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

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What Side Effects Are Possible Following CAR T-Cell Therapy? from Patient Empowerment Network on Vimeo.

Myeloma expert and researcher Dr. Beth Faiman shares an overview of both rare and mild side effects that may affect people who have undergone CAR T-cell therapy. Dr. Faiman also discusses patient monitoring and explains methods to help combat potential issues caused by CAR T-cell therapy.

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.

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

Transcript:

Katherine Banwell:

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.  

Is CAR T-Cell Therapy Right for You? Questions to Ask Your Myeloma Care Team

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Is CAR T-Cell Therapy Right for You? Questions to Ask Your Myeloma Care Team from Patient Empowerment Network on Vimeo.

How can myeloma patients decide if CAR T-cell therapy is right for them? Myeloma expert and researcher Dr. Beth Faiman discusses the role of shared decision-making in patient care and questions to ask the care team when considering CAR T-cell therapy.

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.

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

Transcript:

Katherine Banwell:

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.  

Myeloma Research | CAR T-Cell Therapy Clinical Trials

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Myeloma Research | CAR T-Cell Therapy Clinical Trials from Patient Empowerment Network on Vimeo.

What new CAR T-cell therapies are being studied in clinical trials? Dr. Adriana Rossi shares an overview of alternatives to CAR T-cell therapy, information about the latest CAR T clinical trials, and advice for patients that may be interested in participating in a trial.

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.

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Transcript:

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.  

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

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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

Questions to Ask Your Doctor About CAR T-Cell Therapy

 The Value of Myeloma Support Groups and How to Join

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

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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

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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.   

Understanding CAR T-Cell Therapy | How It Works and Who It’s Right For

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Understanding CAR T-Cell Therapy | How It Works and Who It’s Right For from Patient Empowerment Network on Vimeo.

How is CAR T-cell therapy changing myeloma care? Dr. Adriana Rossi explains how CAR T-cell therapy works to fight myeloma and which patient type is most appropriate for this treatment option.

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.

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 Myeloma Research | CAR T-Cell Therapy Clinical Trials

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Transcript:

Katherine Banwell:

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.