Tag Archive for: risks

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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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.  


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.  

Myeloma Treatment: When Should a Clinical Trial Be Considered?

Myeloma Treatment: When Should a Clinical Trial Be Considered? from Patient Empowerment Network on Vimeo.

 At what point should a clinical trial be an option for myeloma treatment? Dr. Joshua Richter shares his perspective on the appropriate time to weigh clinical trial participation and the potential benefits.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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When should a clinical trial be considered for myeloma treatment?

Dr. Richter:

So, clinical trials are an extremely important component of how we manage myeloma. And I think there are a lot of myths and misconceptions about trials. Trials are not always things to do after everything else failed. From my standpoint, at every point along the way, we should always consider clinical trials, because they offer something really amazing. They offer us access to drugs way before they’re approved.

And the benefit of not waiting until the end, after you’ve been through everything else, is two-fold. One, in order to get on a trial, you need to fit certain criteria, inclusion, and exclusion criteria. You need to have myeloma, but you can’t be so sick from other medical problems that you’re not going to tolerate that treatment well. As such, unfortunately, some patients after they’ve been through all the other therapies may not qualify for a clinical trial, and that can be really upsetting.

The other benefit of doing a clinical trial early on is if you go on a new drug and it doesn’t work, you have all of the other standard of care options available at a moment’s notice. But if it does work and you gain access to a drug way before it’s approved, and it happens to work extremely well in you, you can have an unbelievably long remission and still have all of the drugs that are available. And, potentially, in that time on the drug, new standard of care drugs are approved. It even deepens the well that you can reach into to grab more options. So, at all times along the way, it’s always important to weigh the risks and benefits of what we call standard of care treatment versus clinical trial options.