What potential side effects can occur when myeloma patients are going through CAR T-cell therapy? Dr. Adriana Rossi, a myeloma specialist, reviews possible short and long-term side effects, shares what care partners should be monitoring for, and explains how treatment response is measured.
Dr. Adriana Rossi is 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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Transcript:
Jamie Forward:
What are the short-term side effects associated with CAR T-cell therapy?
Dr. Adriana Rossi:
Absolutely. So, the T cells are part of the immune system. Their job is to grow and expand once they’re in the patient, and pick a fight with the myeloma, which will cause a certain level of inflammation. So, some inflammation is good. But sometimes, they overdo it, and it manifests itself as a fever. We call that cytokine release syndrome. Cytokines are the molecules T cells use to communicate with other members of the immune system. So, this is part of the process we are causing, but we want to keep it in check.
And, in the early days, we were very hesitant to do anything that could harm these precious T cells. But, we’ve learned in time that all of the antidotes, including tocilizumab-bavi (Tofidence) and steroids, don’t harm the effectiveness of the CAR T. And so, we’re very quick to intervene early and intervene with as many tools as we need. And so, that’s really become mostly just the fever. If left untreated, it can lead to low blood pressure and maybe an oxygen requirement.
Again, usually quite easily reversible. When the inflammation happens around the brain or the nerves, we call that neurotoxicity. Specifically ICANS, which is the confusion and neurological deficits that occur with CRS. Neurotoxicity also includes other things like a peripheral neuropathy, cranial nerve palsies like Bell’s palsy has been reported quite frequently. And then, very rarely, delayed neuromuscular toxicities, which again, by patient selection are becoming more and more rare.
And, the last is low blood counts, which we’ve touched on as part of the reason patients need such close follow-up once they leave the hospital. They’re very much at risk for infections, because they’re not making antibodies. Their neutrophils, which is the infantry type white blood cells, are low. And, their T cells are going to be low from the process.
Jamie Forward:
And so, for a care partner, what should they be looking for?
And, when should they contact a member of the healthcare team?
Dr. Adriana Rossi:
I would say contact us anytime there is a question. It’s not too specific. Certainly, any fever. Any sign or concern for infection. And, any neurologic deficit. If someone is not acting themselves, the caregiver’s usually in the best position to recognize that.
Jamie Forward:
Okay. And, what are the long-term side effects?
Dr. Adriana Rossi:
Yeah. We’re still learning. Beyond a year, really there shouldn’t be many. We continue to support the patient until recovery of those antibodies, and T cells, and neutrophils. So, there’s a lot of preventive things. Monitoring and time. And, there are these rare neurological toxicities that have been reported, but they’re much less than one in 1,000. And so, it’s hard to learn or to make any generalizations at this time.
Jamie Forward:
And, as far as monitoring at home once someone gets back home, in the weeks that follow their time in the hospital, are there certain supplies they should have? It sounds like maybe blood pressure? Perhaps a scale?
Dr. Adriana Rossi:
Yeah. So, blood pressure and temperature probably are the two more important ones. We actually do discharge patients with a log, and for those first few weeks, we really would like at least twice a day for these numbers to be monitored. And, it’s patient-specific. So, the less you need, the more we graduate out to fewer measurements and less monitoring.
Jamie Forward:
When it comes to diet and nutrition, are there ways that care partners can help prepare or benefit to a highly nutritious diet? Is there anything related to diet and lifestyle that might be important to know?
Dr. Adriana Rossi:
No. I think there’s no restriction. The important thing is when your appetite is low, your body needs calories. We’re asking your body to get a lot of work done, and it can’t do that without calories. So, don’t be too picky on only eating fruits and vegetables. If it’s ice cream three times a day, go for it. Make sure you’re meeting a caloric intake. Certainly, nutrition is better.
The only dietary restrictions we have are really kind of similar to after a transplant where we’re trying to avoid germs. So, foods that can be cooked, peeled, or washed are really the focus. Things like berries and salads can easily have germs sneak in. So, we do try to avoid those. And again, it’s usually just for that first month or two. Recovery tends to be quick.
Jamie Forward:
Okay. Great. So, have a lot of ice cream on hand.
So, how do you know if the treatment’s working?
Dr. Adriana Rossi:
Well, most patients will have an M spike or light chain change. So, we can follow that by blood tests. And, as with any other therapy, it’s usually a monthly check of those numbers.
And then, we follow the paradigm we see in stem cell transplants at around day 100 doing a bone marrow biopsy and a PET scan.
Again, up to 90 plus percent of patients, will have a complete remission on their blood tests within a month. But, we wait until day 100 to really let that protein have time. There’s a certain time to clear from the system. Check the cells in the bone marrow and really give you full credit for all your efforts.
Jamie Forward:
Okay. Great. So, we’ve sort of touched on this before, but I think it bears reiterating. So, why is it so important that care partners let the care team know about any changes they see in their loved one?
Dr. Adriana Rossi:
I think early intervention really leads to success. Most of the toxicities will respond very well to an early intervention. If left untreated, be it an infection, a neurologic finding, a cell count issue, the longer it happens, the bigger of a problem it is, and the harder it would be to turn around.
So, something that could hopefully be a quick visit to the office could then become an admission to the hospital, and we’d really like to prevent that.
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