What is immune effector cell associated hematotoxicity (ICHAT)? Which myeloma therapies are associated with ICHAT? How is ICHAT managed?

What is immune effector cell associated hematotoxicity? Which myeloma therapies are associated with ICAHT? How is ICAHT managed?

ICAHT stands for immune effector cell associated hematotoxicity.

ICAHT is a fancy acronym for the low blood count issues that we see with T-cell redirecting therapy, specifically Car-T cell therapy and bispecific antibody therapy, and particularly 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, you know, 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 fludarabine and cyclophosphamide lymphoma, depleting chemotherapy that people get before the Car T-cell infusion, occurs. 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’s being infused, the more likely that 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.

So there is now just like for ICANS, this ICAHT, it 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 prolong 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, g CSF 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 romiplostim or Nplate for example, that we frequently will use in this situation. There's an oral drug that functions similarly called eltrombopag that we’ll sometimes use. And then, you know, in the more extreme cases, you know, where patients have very severe drops in blood counts that persist if they have stem cells left behind from a prior transplant, we will give them what we call a stem cell boost. And what I mean by that is 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 cell. So it's a very nontoxic treatment. And that allows the bone marrow to reestablish itself much faster.

To learn more about Car-T cell therapy and other side effects associated with this treatment, visit Health Tree University's immunotherapy module and select Car-T treatment.