Understanding and Managing CAR T-Cell Therapy Side Effects | What You Should Know

Transcript

Katherine Banwell:

What are the side effects of CAR T-cell therapy? And why do patients and their care partners need to be aware of what to expect? 

Dr. Doris Hansen:

That’s a great question. 

So, I think, regardless of what CAR T-cell therapy patients might choose, whether it’s something on clinical trial, or something that is commercially approved, I would say that there’s generally at least two universal side effects from these treatments. 

So, majority of patients will have what is known as cytokine release syndrome, or CRS. Which, the way I describe it to my patients, is having the flu. You have a high-grade fever, so you might have some body aches. You might have a headache. Generally, this is very mild, and it’s what we call Grade 1. But sometimes, it can be more severe. But I’d say this is more universal to any CAR T treatment. 

In addition, patients will have low blood counts from all CAR T-cell treatments and will take a bit of time to recover. And when there are low blood counts, obviously, we have to be very careful and mindful of any infectious complications, and we support our patients with antibiotics and such. 

Now, other side effects from CAR T include neurologic toxicity. So, these T cells do cross the blood-brain barrier, and they can cause what is known as ICANs, immune effector cell-associated neurotoxicity. 

And really, what that presents as, it might be confusion, tremors, wordfinding difficulty. This has, in the commercially approved products, this has occurred in up to 20, 17 to 20 percent of patients. But generally, it’s reversible, and it’s low grade. Rarely, it can be more severe. 

With, particularly, I would say, Carvykti, and some of the CAR Ts on clinical trial, there are what we call non-ICANS neurologic toxicity. So, the unusual neurologic toxicities. They can manifest, for example, as Parkinson’s. So, similar to what you might see with Parkinson’s disease. Generally, if we give CAR T earlier, as I mentioned, in second or third line, the risk of getting this with Carvykti, for example, is very low. But nonetheless, it’s there. It’s about 1 percent, or less than 1 percent. And then, the risk of getting what we know as cranial nerve palsy. 

So, something as Bell’s palsy, where you might have a droopy mouth. or a droopy eye. Generally, that is reversible in 60 to 70 percent of patients. But with Carvykti, in early line, it occurs in about nine percent of patients in clinical trial. With arlo-cel, there is what is known as cerebellar toxicity that is still in development, but it can present as dizziness or unsteadiness. But nonetheless, the likelihood of having these symptoms, or these more aggressive toxicities, generally, it’s very low. 

There’s also long-term follow-up and monitoring, because our patients are generally older and they’ve had a lot of treatments. So, we have to be very mindful in the long term about monitoring what we know as second primary malignancies, or developing another secondary cancer, following the CAR T. And last, but not least, there was a recent update to the FDA label for Carvykti, which includes what is known as IEC. So, immune effector cell-associated enterocolitis. 

So, this just represents as diarrhea, on average, about 90 days or three months following CAR T. The incidence, or the likelihood of something like that happening, is only about 1 to 2 percent, but nonetheless, is a toxicity that we should consider as we counsel our patients with this treatment. 

Katherine Banwell:

One person who’s very important, plays a big role in the healthcare team, is the care partner. So, tell us why a care partner is essential. 

Dr. Doris Hansen:

A care partner is so important. Generally speaking, my patients, when we move forward with CAR T, we do require a care partner, or someone who can be with you. Because at our institution, and I think a lot of major academic institutions, CAR T is given in the outpatient setting. Essentially, patients come in, they get their chemotherapy. They get their CAR T infusion. And then, they get discharged to facility that is close to our institution. 

And they are generally mandated to be in proximity of the institution. In the past, it used to be 30 days. Now, with some new FDA guidance, it’s at least two weeks. But a care partner is important because they might help our patient in different ways. For example, if our patient has a fever, they could help give us a call. They might go to the pharmacy and pick up their medications. Or they might go to the grocery store and might help our patients with making meals or support our patient in any way that they can. 

I don’t expect that our patients with CAR T will be – they should be able to walk. They should be able to come to the treatment center and do all of their daily activities. It’s just, sometimes, a lot of us need help, especially undergoing such a major procedure, to help guide us along the way with certain things. Like I said, cooking. Or if you are feeling unwell, to let us know, and those types of things. And also, driving the patients. 

Because, as it stands, generally, we’d recommend that a patient receiving CAR T does not drive for at least two weeks following CAR T-cell infusion. It used to be eight weeks, but thankfully, that has been rolled back to about two weeks post-infusion. 

Katherine Banwell:

Dr. Hansen, CAR T, of course, has been around for several years now. Are there innovations in improving the patient experience when they’re undergoing CAR T-cell therapy? 

Dr. Doris Hansen:

There are. There’s actually a lot happening. So, when CAR T first got approved, it used to be given in the inpatient setting. Because we wanted to monitor our patients very closely for any safety outcomes, like I mentioned, the CRS and the ICANs, or any other additional problems. However, recently, we’ve seen that we do not need to keep our patients in the hospital for a week, or two weeks. That did appear to be excessive. Currently, CAR T is given in the outpatient setting, which is, I think, nice for the patient. 

They’re able to go outside. They’re able to sleep in a bed that’s not a hospital bed, eat meals that might not be hospital meals. So, I think it’s nice in that regard. But also, we’ve also incorporating a lot of patient-reported outcomes.  

So, we have a lot of studies, actually, that we give our – patient we talk to our patients, right? About their experience, and “What can we do to make this better?” So, having this patient-reported outcome surveys where we ask our patients different questions throughout their treatment journey, so that we know how to improve their experience, or hear directly from our patients. So, we have several ongoing studies that look at that as well. 

And then, there’s some discussion, and some of the centers also do this, where you have, kind of monitoring device that can monitor for fevers, and change in your heart rate, and blood pressure, and things like that. 

So, there’s a lot that’s happening, especially with AI and different devices, where we can directly get the information about, “Is somebody about to have a fever?” Things like that. So, I think science is really advancing forward. But really, the most important first step is moving CAR T to outpatient, and hearing from our patients about how we can improve their experience. 

Katherine Banwell:

Why is it essential for patients to share any issues they may be having with their care team? 

Dr. Doris Hansen:

I think it’s very important. We always tell our patients that, “Anytime you see something, or let’s say you have a headache, or you start to have body aches, any type of side effects, we prefer that they’re reported to us.” Because then, we’ll check the bloodwork and see, “Are there inflammatory markers rising?” Because that could tell us, “Maybe somebody is about to develop a fever, or somebody is about to develop CRS.”  

So, I think it’s really very important to communicate closely with the medical team, because we prefer to be conservative and try to intervene sooner rather than later to make sure that our patients have the best outcomes.