Use of Biomarkers to Predict CAR-T Outcomes | Darren Pan, MD | ASH 2023

Hi, my name is Darren Pan. I am a hematology oncology fellow at Mount Sinai Hospital in New York City. Today, I'll be talking to you about one of the studies that we did recently. We looked at whether inflammatory biomarkers, so whether some of the basic lab tests that we can get just by drawing your blood can help us understand which patients with multiple myeloma will do well following CAR T cell therapy and which ones may not benefit as much. And so, many of you may have heard of CAR T cell therapy, but this is a type of immunotherapy where we take the T cells from your own body, so these are your own tumor fighting cells, and we engineer them in a lab to be hyper focused on specific proteins on the multiple myeloma. And after engineering them, we infuse them back into your patient's body, and there they can do the work of going ahead and bringing that multiple myeloma into remission. Now, CAR T cells are very effective. There's already two products that have been approved. One is called a Beckman or a Ida cell, and the other is called CAR-VicT or a Cilta cell. But one thing that we know with CAR T cells is they come with a set of side effects that have to do with the inflammation that the infusion of the CAR T cells induces. And so, we know that there are some patients who will do fairly well with CAR T cells, and these reactions are very mild, whereas for other patients, the reactions can be more severe and more difficult to control. So with this study, we're trying to find out whether some of these basic lab tests that we can get before you start CAR T cell therapy, whether these labs could help us determine which category you as a patient might fall into. One of our first findings was that the lymphocyte count, so that is when we draw your blood, how many T cells and B cells you have in your body can help us understand your risk of neurotoxicity following CAR T cell therapy. So patients who had higher lymphocyte counts at baseline of greater than or equal to 1,000 had a much higher risk, about five-fold, of having neurotoxicity than patients who had low lymphocyte counts of less than 500. And the way neurotoxicity usually manifests is as confusion. Sometimes it can be as simple as when you're getting CAR T cell therapy, they'll have you write your name, and it can be as simple as the writing changing just slightly. Those are early signs that can help us control these adverse effects early, but using this biomarker, the lymphocyte count, we can better understand whether you're at risk of getting that side effect or not. The second thing that we found was that two more lab tests, fibrinogen and ferritin, can help us see whether your risk of progression-free survival and overall survival is lower. And what we found is that having high ferritin and high fibrinogen overall was associated with poorer outcomes following CAR T cell therapy. And so all of these aren't alone going to allow your physician to decide whether or not to pursue CAR T cell therapies in your case, but they're additional tools that your clinician can use to better understand whether CAR T cell therapy or an alternative is right for you.