CAR-T in Myeloma Patients with Extramedullary and Paramedullary Disease | Darren Pan, MD | ASH 2023

Hi, my name is Darren Pan. I'm a hematology oncology fellow at Mount Sinai Hospital in New York City. Today I'll be talking about one of the studies that we recently conducted on extramedullary disease and perimedullary disease as they relate to outcomes in multiple myeloma patients who are receiving CAR T cell therapy. So just to review, the majority of patients who have multiple myeloma have these tumor cells living in their bone marrow, so inside of the bone itself. In a subset of patients though, these tumor cells can find a way to grow outside of the bone marrow, which is their natural home, and there's two main ways that this can occur. In one, which we call perimedullary disease, the tumor cells can grow out from the bone and appear as a tumor that's attached to the bone. The second way is some of these tumor cells can escape into the blood and seed into tumors that are in areas totally disconnected from the bone. So it can be, for example, in the liver, in the soft tissue, like under the skin, etc. And most clinicians would consider this category extramedullary disease. And so you have these two types of tumors outside of the bone, a perimedullary where it's still attached to the bone, and extramedullary where it's no longer attached to the bone. What we've increasingly understood in recent years is that these two types of tumors do not have the same effect on your prognosis. In fact, patients who have perimedullary disease, although they oftentimes, it's a negative prognostic factor, meaning that having no soft tissue is still better, having truly extramedullary disease that's not attached to the bone seems to be the worst prognostic factor. And in our study, we evaluated how these would affect CAR T-cell therapy, which is one of our newest and most effective therapies. What we found was that with CAR T-cell therapy, actually patients with perimedullary disease, the soft tissue masses that are attached to bone seem to do just as well as patients who don't have any soft tissue lesions at all. Unfortunately, patients who have extramedullary disease not attached to bone continue to have poorer outcomes, even with CAR T-cell therapy. And so this is showing us that better understanding why extramedullary disease behaves so differently from disease elsewhere in the body is going to be a real priority in the coming years. Another thing that we found was that with CAR T-cell therapy, and actually most other therapies as well, but as patients receive more lines of therapy, their risk of having extramedullary disease relapse increases. So in our study, there were about a quarter of patients who had extramedullary disease when starting CAR T-cell therapy, but after CAR T-cell therapy, this increased to about half of patients. The last thing that we found was that there may be an importance of the size of the extramedullary disease in the body. And so for patients who had, if you add up the sizes of all of the extramedullary tumors, if that amounted to the size of a tennis ball or larger, the chance of having a response at all was much lower. And many patients progressed quite early after receiving CAR T-cell therapy. Whereas for patients who had tumor sizes cumulatively that were less than the size of a tennis ball, in most cases, they still had a response, even if the response was not as long lived as we'd hoped. And so ultimately, I think that we've shown that with CAR T-cell therapy, paramedullary disease seems to not be as important as a prognostic factor because these patients do very well with immunotherapy. Whereas extramedullary disease, we still have a lot of work to do. It's an area that we have to study more. Actually, can you do that last bit one more time? Okay. So ultimately, I think what our study has shown is that with CAR T-cell therapy, patients with paramedullary disease can often be just as well as patients with just disease only inside the marrow. Whereas when it comes to extramedullary disease, we still have a lot of work to do. Perfect. Thank you so much. Yeah, thank you.