BETA - What is immune effector cell-associated hematotoxicity?

Immune-based therapies can be powerful tools against cancer, but they can also affect your blood counts. This is called immune effector cell-associated hematotoxicity, or ICAT. In this video, we'll explain what that means, what to watch for, and what patients and caregivers should know. So ICAT, which is I-C-A-H-T, stands for immune effector cell-associated hematologic toxicity. And it's basically a fancy way of talking about low blood counts that can occur after CAR T cell therapies. So we expect that patients will temporarily have low blood counts after CAR T cells, because they get chemotherapy for three days, fludarabine and cyclophosamide, before the CAR T cells go in. And that's by design. We want to temporarily lower your white blood cell count to make room for the CAR T cells to expand. However, some patients don't have the expected recovery after a few weeks after that chemotherapy wears off. They have, unfortunately, more prolonged what are called cytopenias, low blood counts, meaning low white blood cells, low red blood cells or hemoglobin, and low platelets. So that's what we call ICAT, this hematologic toxicity that can sometimes extend for several months after the CAR T cells go in. And in some cases, if it's severe, it can lead to a need for blood transfusions, platelet transfusions, or what's called growth factor support, nupagen or GCSF or medicines to boost your platelets. What are some signs and symptoms of ICAT? How is ICAT diagnosed? So ICAT is really diagnosed just by blood counts. What you might feel are more fatigue, for instance, if you have low hemoglobin level, you're very anemic. There may be easy bruising or easy bleeding if your platelets are low. And then there's some higher risk of infection if the white blood counts are low. But you don't really feel badly from ICAT itself. It's really just a description of having low blood counts, like you get from stem cell transplant or any other process that affects the bone marrow. What types of patients may be at greater risk to develop ICAT? We're learning a little bit more about the types of patients who are at risk for this complication. It's often patients who have low blood counts even before they get the CAR T cells, probably because they've had a lot of chemotherapy in the past. Or patients who seem to have some baseline inflammatory state in their body. They may have high ferritin levels or high C-reactive proteins. So these can predict for this ICAT later. When it comes to CAR T cell therapy, there's a number of factors that go into play as far as low blood counts after receipt of CAR T cell therapy. So there's the burden of myeloma in the bone marrow going into CAR T cell therapy that plays a factor. The baseline blood counts going into CAR T cell therapy can factor into this. The three days of fluderabine and cyclophosphamide lympho-depleting chemotherapy that people get before the CAR T cell infusion. The type of prior therapy that a patient has had. Have they been transplanted or not? How many prior lines of therapy they've had. If they've been transplanted, if they've had multiple lines of therapy, their bone marrow reserves may not be quite as robust. And that may lead to more exaggerated drops in blood counts after CAR T cell therapy and more prolonged drops in blood counts. And then there's the actual CAR T cell therapy itself. So you can envision these CAR T cells infiltrating the bone marrow, attaching to myeloma cells and killing them. And in that context, there's a large number of what we call cytokine proteins that are liberated as a result of that immune attack on the myeloma cells. And some of those cytokines can actually suppress the bone marrow's ability to make normal blood cells, white blood cells, neutrophils, red blood cells, and platelets. And that can lead to a prolonged period of time where the blood counts are low. And it makes sense that the more disease that you have in your bone marrow at the time that the CAR T cell is being infused, the more likely that's going to be problematic. And then for patients who have more severe types of cytokine release syndrome, there's this unusual phenomenon called HLH, which is another funny acronym for an intense activation of the immune system, with the end result being that there's these funny Pac-Man-like white blood cells called macrophages that come into the bone marrow and start gobbling up normal bone marrow. And recognizing that rare complication of CAR T cell therapy is incredibly important because the treatment of that is going to be different. There is now, just like for ICANNs, this iChat has a scoring system in place where you can determine the severity of low blood counts within the first 30 days of CAR T cell therapy and afterwards. And there's also a score that you can use to predict what the likelihood is of low blood counts and prolonged low blood counts after CAR T cell therapy. And that's important because for folks who have more exaggerated drops in their white blood cell count, neutrophils particularly, and if that persists for a long time, they are going to be at higher risk of severe infection and that could lead to potentially detrimental outcomes for those patients. The best practices are supportive care. So that largely revolves around blood product transfusion support. And that includes red blood cell transfusions for the anemia and platelet transfusions for the low platelet issues. Growth factor support is quite helpful. So growth factors for neutrophils, GCSF or neupogen or its equivalent or long acting versions of that can help bring the neutrophil count up a bit faster. We'll sometimes use platelet stimulating agents. There's something called ramiplastum or an N-plate, for example, that we frequently will use in this situation. There's an oral drug that functions similarly called altraambopeg that we'll sometimes use. Fortunately, the vast majority of patients do eventually recover their blood counts. And so if you look at the clinical trials with IDA cell or CILTA cell, almost all the patients by three months and certainly by six months have had recovery of their counts. But there are a small subset, unfortunately, that may have this prolonged ICAT. And in that case, we will sometimes do something called a stem cell boost, where if we have frozen stem cells from when they collected many years ago, we can infuse a little bit of those stem cells and then those blood counts will come up. So that's how we manage it. We'll take those remaining stem cells out of the freezer. We'll thaw them out and we'll infuse them back into the patients. No high dose chemotherapy beforehand. We just give the cells. So it's a very non-toxic treatment. And that allows the bone marrow to reestablish itself much faster. Hypogammaglobulinemia is a different potential toxicity where the body doesn't make enough good antibodies to help fight infections. And so it turns out that these CAR T cells, they don't only target the myeloma cells, they target normal plasma cells, which are the immune cells in our body that help us make antibodies. And so hypogammaglobulinemia is a term that means you have low immunoglobulins or antibodies in your blood, particularly IgG or IgM or IgA. And this is very common in myeloma in general, but can become worse after you've had these CAR T cells. And so many patients will develop this after CAR T's, often for many months, even up to a year or more. And the way we treat it is by giving what's called IVIG, intravenous immune globulin infusions. And these are typically once a month infusions of good antibodies that help boost up your immune system and help you fight off infections. Learning about side effects like immune effect or cell associated hematotoxicity can help you feel more prepared and confident as you move through CAR T therapy. If you'd like to continue learning, we invite you to watch the other videos in Health Tree's CAR T treatment course, where we walk through each step of the CAR T journey with clear explanations and expert guidance.