Tag Archive for: neurotoxicity

What Is CAR T-Cell Therapy for Myeloma?

What Is CAR T-Cell Therapy for Myeloma? from Patient Empowerment Network on Vimeo.

How does CAR T-cell therapy work to treat myeloma? This animated video provides an overview of the CAR T-cell process, explains which patient this treatment could be appropriate for, and reviews potential side effects.

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Transcript:

CAR T-cell therapy is a type of treatment in which a patient’s own immune system cells, also known as T cells, are reprogrammed in a laboratory to attack cancer cells.  

The process involves removing T cells from the patient’s blood. Then, the T cells are sent to a laboratory where a gene for a special receptor that binds to a protein on the patient’s cancer cells is added to the T cells. The special receptor is called a chimeric antigen receptor.  

When this process is complete, the cells are put back into the patient’s body by infusion. The altered T cells then attack and destroy cancer cells in the patient’s body. 

In myeloma patients, the FDA-approved CAR T-cell therapies recognize a protein called B.C.M.A. on the surface of myeloma cells. 

Now that you know how CAR T-cell therapy works, who is CAR T-cell therapy right for? 

  • While still a new treatment, CAR T-cell therapy is currently approved for people with relapsed or refractory multiple myeloma who have already received four or more lines of therapy. 

While every patient reacts differently to CAR T-cell therapy, some of the potential side effects may include: 

  •  Cytokine Release Syndrome, which occurs when the immune system responds to infection or immunotherapy drugs more aggressively than it should. Symptoms may include fever, nausea, fatigue, and body aches.
  • Another potential side effect is neurotoxicity, which may cause negative effects on the nervous system such as confusion, difficulty speaking or understanding, loss of balance or consciousness, tremors and seizures. 
  • And blood count recovery can be slower following CAR T-cell therapy.   

So, what should you ask your doctor about CAR T-cell therapy? 

  • Is CAR T-cell therapy available at this cancer center? 
  • Is CAR T-cell therapy an option for me now or in the future? 
  • What is the cost of this therapy? 
  • What are the risks and benefits of this approach? 
  • What can I expect during the recovery process? 

To learn more about innovative myeloma therapies and to access tools to help you become a pro-active patient, visit powerfulpatients.org.  

What Are the Risks of CAR T-Cell Therapy?

What Are the Risks of CAR T-Cell Therapy?  from Patient Empowerment Network on Vimeo.

Dr. Melissa Alsina, a myeloma expert from Moffitt Cancer Center, reviews the potential side effects of CAR T-cell therapy for myeloma patients, and discusses how these side effects may be managed.

Dr. Melissa Alsina is an associate professor of medicine in the Blood and Marrow Transplant Program at Moffitt Cancer Center in Tampa, Florida where she also serves as head of the Multiple Myeloma Transplant Program. Learn more about Dr. Alsina, here.

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Transcript:

Katherine:

What are the risks of CAR T-cell therapy? 

Dr. Alsina:

So, in myeloma, it is, in general, pretty safe. There are two main – well, actually, I would say three main side effects that we can see with CAR-T. Number one is called cytokine release syndrome, and we are getting these cells from the patient’s immune systems, sending them a lab to be manufactured so that they can recognize this protein, BCMA, in the myeloma cells. 

And then, those cells are grown, so essentially, what we’re doing is that we’re taking the immune system of the patient, and we’re making it very specific against the myeloma cell. And then we’re growing it, so we’re making a hyperactive immune system, and then giving it back to the patient. And then, those cells, they are going to go ahead and react against the myeloma cells and start killing the myeloma cells, and in doing that, that reaction, that immune reaction will elicit release of a lot of proteins – cytokines – and that can cause side effects. 

When that happens, that is called cytokine release syndrome, and the most common finding with that is a fever. Patients can have a high fever. And then, it varies depending on the CAR-T that the patients are getting. So, for example, with this Abecma, usually, the reaction happens right away after you get the cells – the next day, so that’s why these patients, we admit them to the hospital because we know that this cytokine release syndrome is going to happen right away.  

And, it could be just a fever. In the majority of the patients, it happens like this, is just a fever, but it may be about 20 percent of the patients, that reaction can be more severe, and it could be a fever with low blood pressure or shortness of breath, and it could be a fatal complication, but that’s very, very rare.  

And we know – we can identify, obviously, when it’s happening, and there’s a medication that we can give to actually sort of counteract that reaction and don’t let it progress, and in the majority of the patients, that works quite well.  

Katherine:

What other side effects are there for CAR T-cell therapy? 

Dr. Alsina:

Yeah, so besides the main one that I discussed, cytokine release syndrome, the other thing that could happen is neurotoxicity, meaning that T cells can actually cross to the brain and cause toxicity in the brain, and depending on the type of CAR-T that the patient is getting, it could be less or more risk.  

But essentially, what could happen is that the patient could have some aphasia, like for example, difficulty finding words. It could also be just a headache. Patients could have seizures, so we do give the patients medication to prevent seizures while they are undergoing CAR-T. 

They can have difficulty writing, so we make every patient write a sentence every day to make sure that’s not being affected. And we do a mini mental status every day. Every day, we’ll go see the patient and ask them 10 different questions, like “Where are you? What day is it? Who’s the president?”, we show them an object, and so on so we can monitor these things very closely. If we see any changes, then we can intervene. Usually, for neurotoxicity, we give steroids. 

The good news, though, is that this is very rare. With Abecma, it’s very rare that a patient would have severe neurotoxicity. With ciltacabtagene autoleucel (Carvykti), which is the one that was approved more recently, from 100 patients that were treated, there were five patients that had this delayed neurotoxicity, some of them with movement disorders, like Parkinson’s-like systems, and these were delayed. These didn’t happen in the first few weeks. 

But we learned what are the risks associated with these, the majority of the patients that have very high tumor burden, so what we do is that we monitor the patients very closely, especially the patients with high tumor burden. The ideal situation is that we can control the disease a little bit better before taking them to CAR-T, but even when that’s not possible, what we do is that we intervene early on if we see that these patients are getting any side effects and being more aggressive with the intervention. 

And then, the third, more important side effect is these CAR-T cells can prevent blood counts to recover. For CAR-T, we give chemotherapy.  

That would allow the T cells to expand, and this chemotherapy can drop the blood counts, but usually, they recover quickly, but in some patients, this recovery doesn’t happen quickly, and patients can have low counts for months, and obviously, that would bring increased risk of infection. 

So, that is a potential complication, especially in patients that have received a lot of prior therapies, and it’s not common that a patient would take a long time, but it could happen, and sometimes, occasionally, we’ve had to give these patients a stem cell boost from stem cells that we have stored to actually make their counts recover. So, those are essentially the three most common complications, but in general, it’s a treatment that is well tolerated and very manageable, and I can tell you the majority of the patients that I’ve treated, they’ve said this is easier than a transplant.  

What Are the Side Effects of Myeloma Immunotherapy?

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.

Related Resources:

How Does Immunotherapy Treat Myeloma?

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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.

Immunotherapy: Which Myeloma Patients Is It Right For?

Immunotherapy: Which Myeloma Patients Is It Right For? from Patient Empowerment Network on Vimeo.

Dr. Krina Patel, a myeloma specialist and researcher, explains how newer therapies, such as CAR T-cell therapy, are being used in myeloma and which patients these treatments are most appropriate for.

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.

Related Resources:

How Does Immunotherapy Treat Myeloma?

What Are the Side Effects of Myeloma Immunotherapy?

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Transcript:

Katherine:   

Now, in reference to immunotherapy and CAR T-cell therapy, who are these types of treatments right for?

Dr. Patel:    

So, I think it’s really exciting that we finally are getting standard of care therapies for all these new immune therapies. So, our first CAR T for myeloma got approved a little over a year ago. Our second CAR T got approved just a couple of months ago, and we’re hoping our first bispecific will be approved in just a couple months.

Our fingers crossed. On the clinical trials, I will say our patients who had a good performance status, meaning they’re able to do everything else normally life-wise, those are the patients that got onto those clinical trials; and the reason is safety-wise.

So, T cells when we use them to kill myeloma, they release cytokines or enzymes, you can say, that are inside the T cells and that’s what they use to communicate with other immune cells to come help them kill.

Those are the same cytokines that make people feel really ill when they have the flu, for instance. So, as our immune system tries to fight infections when people get fevers, they feel chills, they feel just fatigued and tired, it’s those same kind of cytokines that, even when you try to kill the myeloma with T cells, people can get that same type of symptoms.

And really, the main, fevers and things like that, we can take care of. But when patients’ blood pressure drops or if their oxygen levels drop really low, that’s where we can run into some trouble. Now, the good news is, in myeloma, most of these new therapies don’t cause really bad CRS [Cytokine Release Syndrome] or really bad neurotoxicity that we can sometimes see. And so, thankfully most patients are okay, but really it’s making sure that none of our patients have bad toxicity. So, most of our myeloma patients, I will say, are eligible for these therapies. However, if someone has really bad heart disease or really bad lung disease, those are patients that maybe these are not the right therapies for.