Tag Archive for: ICANS

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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Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

Advice for Myeloma Patients Undergoing CAR T-Cell Therapy

 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:

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.  

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.

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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.   

CAR T-Cell Therapy | What Are Potential Complications?

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CAR T-Cell Therapy | What Are Potential Complications? from Patient Empowerment Network on Vimeo.

CAR T-cell therapy may cause complications and side effects that their care partners should be aware of ahead of time. Expert Dr. Shambavi Richard reviews possible side effects, including cytokine release syndrome, and how patients are monitored during their hospital stay post-procedure.

Dr. Shambavi Richard is Co-Lead Physician for the Myeloma CAR-T Programs at Mount Sinai Tisch Cancer Center. Learn more about Dr. Richard.

See More from The Care Partner Toolkit: CAR T-Cell Therapy

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Transcript:

Katherine:

Dr. Richard, what are the potential side effects or complications of CAR T-cell therapy? 

Dr. Richard:

So, there are several possible side effects with CAR T therapy.  

It’s a little different from an autologous transplant. And I bring that up just to say because they are both cellular therapies, so are frequently compared and contrasted with autologous transplants which we have had for about three decades now. So, the main side effect after CAR T therapy is something called CRS or cytokine release syndrome. So, that happens when CAR T cells recognize the myeloma cells and kill them. A host of chemicals called cytokines are released in the body. And this can make a person feel like they have a bad case of the flu. So, it may be things like fevers, chills, body pains, headaches, loss of appetite, nausea, fatigue.

So, these are some common symptoms of cytokine release syndrome. But these are the milder forms, so in more severe cases of cytokine release syndrome, you can have things like drop in blood pressure, drop in oxygen levels, needing supplementation with oxygen.  

Or in terms of drop in pressure, they may need fluid resuscitation or sometimes even pressors, blood pressure medications that help to boost the blood pressure. So, that’s one major side effect. Another is something called neurotoxicity.  

So, you can have neurological side effects from CAR T therapy which when it occurs in the setting of CRS, that’s called ICANS or immune effector cell-associated neurotoxicity syndrome. That’s what that acronym stands for. And it has a constellation of symptoms such as confusion, disorientation, difficulty with some common everyday tasks. The handwriting may go off, attention deficit, things like that. But then in more severe forms of ICANS, you can actually have lethargy, coma, seizures, brain edema, so much more scary things.  

Then there is another form of toxicity called delayed neurotoxicity which looks completely different. Now you have things like Parkinson’s disease or neuropathies. Either cranial nerve neuropathies or peripheral neuropathies, Guillain-Barre which is a kind of ascending paralysis. So, all of these are also possible as neurotoxic side effects from CAR T therapy.

Aside from these, there is another which is called HLH or macrophage activation syndrome or hemophagocytic lymphohistiocytosis syndrome wherein patients can have organ toxicity, a spiking ferritin levels, new fevers, new neurotoxic symptoms, additional lab abnormalities such as liver function test abnormalities. So, these are other forms of just general CAR T-cell toxicity.   

Then in addition to these, you can have infections, prolonged blood count abnormalities, cytopenia as we call it which can affect the white cells or the platelets or anemia and things like that. So, these are also possible. And then finally things like second primary malignancies which can happen, other malignancies that can happen that may be related to CAR T therapy. A lot of these are still being studied. We don’t have a good understanding of how frequently this happens. But these are all possible side effects of CAR T therapy.  

Katherine:

Do any of the complications have to result in hospitalization? Or can patients be treated outside the hospital?  

Dr. Richard:

So, the way things stand now, and this may be slightly different depending on the specific CAR T product.  

But we generally keep patients hospitalized for the first two weeks after the cell infusion. Most of the side effects such as the CRS and the ICANS tends to occur during this hospitalization phase. HLH and delayed neurotoxicities can occur while they’re still in the later phases of the hospitalization, or it can occur late after they get discharged from the hospital. Infections and cytopenias of course can happen for a while following CAR T therapy.

Once they are discharged from the hospital, we ask that they stay close to us, usually within an hour or two of the hospital so that they can quickly come back in if there’s any issues. We see them quite frequently once they get discharged from the hospital. I see them at a minimum of once a week, more frequently at least a couple times a week, or even three times a week depending on what their blood count needs and monitoring needs are.  

So, we have them stay close to the hospital if they are far away. And the sponsor and our social worker, insurance can work together to figure out how to help them with the hotel costs if they have to stay close to us. So, that’s for an additional two weeks after they’ve discharged from the hospital. Following that, patients go back to their homes, but we still follow them quite frequently depending on what their needs are in terms of possible side effects. 

What Are the Side Effects of Myeloma Immunotherapy?

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What Are the Side Effects of Myeloma Immunotherapy? from Patient Empowerment Network on Vimeo.

Myeloma specialist and researcher Dr. Krina Patel discusses the common side effects of immunotherapy and reviews tools that may be used to prevent complications.

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. Learn more about Dr. Patel, here.

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Transcript:

Katherine:   

Are there other side effects that patients should know about and side effects that they might experience?

Dr. Patel:  

Yeah, so neurotoxicity is one that we don’t see as much as we see in lymphoma patients, which is again great but sometimes people can get something called ICANS, which is a type of neurotoxicity in the first 30 days after CAR T.

And basically, it can be as bad as seizures, but thankfully we don’t see that very often, or I haven’t seen it at all. But it can cause confusion. It can cause people to be extra sleepy. So, we have different treatments that we give to turn that around. Longer term, really, the big side effects are the counts being low. So, what we call cytopenias. So, white count, hemoglobin, platelets.

And so, that is something we see quite often in our patients who have had a lot of therapy for myeloma already, and then are getting something like CAR T.

So, a lot of my patients will still need transfusions even a month or two or three after, and we’re giving GCSF to help their white count come back up, et cetera.

Katherine:    

What’s that?

Dr. Patel: 

So, G-CSF is basically a growth factor that helps your neutrophil; so, a different type of white blood cell – come back up, which helps fight against bacterial infections.

So, it’s the same medicine for anyone who’s had a stem cell transplant. It’s the same medicine you get to get your stem cells into your blood but it’s at a lower dose. But again, it’s to avoid infections, to help present bacterial infections. The other one is infections can also be caused because of low IgG levels or what we call immunoglobulins; these are our antibodies that we have.

And the good news is, when CAR Ts or bispecifics or some of these immune therapies work really well, they’ll kill as many myeloma cells as we possibly can.

But they also kill good cells. So, they kill good plasma cells that make us antibodies and good B cells that make us antibodies. So, when that happens, people’s IgG levels will go down and that puts you at risk for infection too. So, we actually aggressively give people IVIG to help prevent those infections.