How can the side effects of CAR T-cell therapy be managed? Dr. Danai Dima reviews the most common complications that patients may experience, including cytokine release syndrome, neurotoxicity, and infection risks, while also touching on some more rare effects of CAR T-cell therapy. Dr. Dima discusses how these side effects are treated, why most are temporary, and what patients can expect in the weeks and months following the CAR-T process.
Dr. Danai Dima is Assistant Professor of Hematology and Medical Oncology at Fred Hutchinson Cancer Research Center in Seattle, WA. Dr. Dima specializes in treating patients with multiple myeloma and other plasma cell disorders. Learn more about Dr. Dima.
Related Resources
Transcript
Jamie Forward:
Side effects are often a common concern for CAR T-cell therapy patients. So, what are the most common issues that patients may face?
Dr. Danai Dima:
So, the most common early complication of CAR T-cell therapy is called cytokine release syndrome. So, cytokine release syndrome occurs when the infused CAR T cells activate, and they release inflammatory signals.
The most common symptoms are fever, and less frequently patients can have more severe symptoms such as low blood pressure, high heart rate, and low oxygen levels. Usually, cytokine release symptom occurs within the first weeks after the infusion.
And it’s very, very treatable. We recognize that early. And we use medications that suppress the inflammation. These medications can be tocilizumab (Actemra), our steroids, and in combination with supportive care such as intravenous fluids.
So, we also see less frequently early neurotoxicity or we call it immune effector cell-associated neurotoxicity syndrome. This is when the CAR T cells affect the brain and the nervous system. Most common symptoms here are first, confusion, some difficulty speaking, and difficulty writing. Some patients have headaches.
And if symptoms are more severe, which is pretty rare but can happen, people can have seizures or not responding. Also, early neurotoxicity occurs within the first week or 10 days, always depends on the product.
And most cases are reversible with the use of steroids and close monitoring.
Another side effect is low blood count, or we call it cytopenia. So, many patients can experience prolonged low levels of red cells, white cells, or platelets.
And sometimes, a blood product transfusion or growth factors might be necessary in these patients. So, cytopenia can increase the risk of infections, fatigue, or bleeding, but usually these improve between month three to six post-infusion. And last, I think one of the main adverse events that we need to have in mind are infections.
So, due to the immune suppression from the CAR T cells and the low white cell counts, patients are at higher risk of bacterial, viral, and fungal infections, especially within the first few months after the infusion.
And this is why prophylactic antibiotics after the infusion are essential and also sometimes intravenous immunoglobulins.
Jamie Forward:
Well, thank you for that. And, of course, CAR T-cell therapy has now been around for sort of a while. So, are there any advances that are being made in managing the side effects of CAR T-cell therapy?
Dr. Danai Dima:
I think for cytokine release syndrome and early neurotoxicity, it’s pretty clear that we use tocilizumab and steroids. And with these medications, it’s really easy to manage those side effects. And basically, patients feel much better after a couple of days. I would say overall, early toxicities, we know a lot about them. We have a lot of data, real world data and clinical trial data.
And all the methods and strategies we use are pretty effective. Even, as I – patients with low blood counts, we can support them for a few weeks with transfusions or growth factors. And then, these patients tend to get better and better after month three post infusion. So, we really don’t need to implement anything novel there. And for infections, it’s very, very important for patients and caregivers to make sure that they take their prophylactic antibiotics because this way, we know that we prevent what we call opportunistic infections. And these infections are basically infections that in healthy individuals with good immune systems, they don’t really happen.
But if your immune system is really low, then they can occur, so prophylactic antibiotics are very important, and also the use of intravenous immunoglobulins.
Now, there are some other side effects, more rare but more severe, such as delayed neurotoxicity. And this can present with cranial nerve palsies or even parkinsonism. For these side effects, unfortunately we don’t really know much. We’ve been using drugs that basically kill the CAR T cells in an effort to improve the symptoms. And these drugs include cyclophosphamide (Cytoxan) or sometimes intrathecal chemotherapy, but we’ve seen especially for parkinsonism, we don’t really have great outcomes. Most of the times, this is irreversible.
The good thing is that it’s really, really rare, around 1 to 3 percent of patients. As far as cranial nerve palsies concerned, so we’ve seen that with steroids, they tend to get better over time.
Some other adverse events, long-term adverse events that could happen with CAR T include secondary primary malignancies such as some hematologic neoplasms including leukemia and lymphoma. Again, if that happens, in those instances we just have to treat those patients according to the available protocols we have. And there is another more rare symptom that has been described. It’s called basically enterocolitis. It’s just an inflammation of the gut. And steroids and supportive care there are important.
Jamie Forward:
And it sounds like those are more rare.
Dr. Danai Dima:
Exactly. These are more rare. And unfortunately, we don’t really have a lot of novel agents that are efficacious. So, different institutions might use different things, but nothing is evidence-based, or nothing has really proven to reverse those adverse events, unfortunately.
