Join Dr. Michael Zinner., CEO and Executive Medical Director at
Miami Cancer Institute and Dr. Guenther Koehne, Deputy Director and Chief of Blood & Marrow Transplant, Hematologic Oncology and Benign Hematology, on the first episode of The Debrief as they discuss some of the latest advancements in hematology. mm hmm. Hi, I'm dr Michael Zinner ceo of Miami cancer Institute, a part of baptist health South florida. Today I have dr gunther kona with me to talk about hematology oncology which are blood and bone marrow cancers and is one of the best in the world in his specialty. So, Gunther, thank you for joining us. Well, let me open it up with a general question. Tell the audience what kind of cancers you treat and what they are? Well, human logic malignancies are a variety of blood cancers if you want. That includes leukemia, acute leukemia, chronic leukemia, acute myeloid acute lymphoblastic leukemia, multiple myeloma, myelodysplastic syndrome, milo proliferated disorders and a variety of others all covered under the title of hematology malignancies. There have been a lot of advances in cancer over the last decade. What kinds of advances have you seen in the last decade that have changed the way you approach this disease? Well, that is a very good question and very exciting advances made over the last few years. If you want. We developed a lot of novel therapies that move away from additional chemotherapy and are either targeted therapy that allow us to go into the pathway of a malignant cell to interrupt this in the proliferation of the cancer cell or more importantly in addition, all the immuno therapeutic approaches that we have. And there are lots and of them, they are slightly different. The audience may have heard about the chimeric antigen receptor t cells that play a pivotal role now in the treatment of leukemia, non hodgkin lymphoma multiple myeloma. There are other varieties of immuno therapeutics that are also targeting the myeloma cell or the leukemia cell by having an antibody that has a second binding arm to a cd three or a T cell which are called by specific antibodies. So with this the antibody can attach to the myeloma or leukemia cell and bring the T cells to the site. And thirdly we have a variety of antibodies that have had their tail and a toxin. So what that that means is that the antibody binds to the to the malignant cell and the toxin at the end gets incorporated and kills the cells. So there are three different varieties that I mentioned already. And then there are subcategories within which has been a significant advance and all in all away from chemotherapy more towards immunotherapy. You know, it sounds like what you're describing are like smart bombs at one end it knows how to attach to the cancer cell, but at the other end it's got the bomb to blow up so that that cell goes away. That's exactly right. And so the smart bomb is targeting the malignant cell, whereas chemotherapy targets all the cells that are proliferating and that's really where the where the field is moving away from. Now. You recently organized Miami cancer institute's third annual summit of the Americas on immuno therapies and human theological malignancies. Tell us what you did there and what you can share with us about that experience. Well the reason for this goes back to what I just said. So there are so many new developments with respect to novel approaches of how to treat patients with hematology malignancies. And in fact, as excited as we are, we don't really necessarily know how to best implement them or whether or not they need to be combined or whether or not they need to be sequenced. So to give one example, the car t cells, chimeric antigen specific t cell antigen receptor t cells that are being utilized for the treatment of non hodgkin lymphoma, acute lymphoblastic leukemia and now also for multiple myeloma, have a great opportunity to bring a patient back into remission, but we really don't know. And that has been a hot debate back and forth whether or not it will replace, for example, autologous stem cell transplantation or and I am a strong believer, it may even enhance the number of transplants that we can perform because we have another opportunity to get the patient back into remission. Once they have a relapse refractory disease and then consolidate with autologous stem cell transplantation here at Miami Cancer Institute, were very interested in progressing in the field and doing research and I know your research is really cutting edge, particularly around things like decreasing the complications of bone marrow transplant. Things like graft versus host disease share with us about graft versus host disease and what you specifically have proven with your research. So that goes to the allergenic stem cell transplantation or donor derived stem cell transplantations that have a great curative potential for for most of the leukemias, relapse refractory, non hodgkin lymphoma and other diseases. The limitation has been for all of the donor derived stem cell transplants. The side effect profile, which is summarized as graft versus host disease and that is basically induced by the T lymphocytes that come with a transplant from the donor's stem cell product and can attack the healthy tissues such as the gut, the skin, the liver and other organs, which is the most feared complication following stem cell transplantation. So if we can do away with graft versus host disease, then we will certainly improve outcome overall outcome of allergenic stem cell transplants. And one way to do is to purify the stem cells from the donor Before in we infuse the whole stem cell product which we call transplantation. Now that's possible. And 11 because the stem cells have a unique marker that is called C. 34 we can bind to these stem cells a monoclonal antibody that is an anti cd 34 monoclonal antibody that is conjugated with an iron particle. So now once they bind to the stem cells we'll flush the whole product through a magnetic field and the stem cells get attached to the magnet. Everything else flushes through and everything else in this case are the donor t cells that have the capacity to reduce graft versus host disease. So in other words, what we do here at Miami Cancer Institute is a C. 34 selected telegraphed which could also be called a T cell depleted transplant product. And with that we don't see graphics of sos disease to that extent at all, there is a limited number of patients with mild graft versus host disease remaining but relatively easily treated if it occurred. So if I understand you correctly, when you do the bone marrow transplant there are good guys and bad guys in there and you can pull out the good guys and get rid of the bad guys And that's why you do the transplants that are successful. That's another step though. So now that's the next just recently FDA approved clinical trial that I submitted. And so now what we do first step is to select the stem cells deplete most of the T cells. There's a minimal amount of donor t cells remaining. That's okay, they don't induce necessarily. As just mentioned the graft versus host disease. But now what we can do within the leftover product select T cells that we want. And there are separate subgroups of different subgroups of T cells and the bad guys. Uh the ALfa beta receptor positive T cells and the good guys are the gamma delta positive T cells. So now in the second step we can eliminate from the product the alpha beta receptor positive T cells and infuse calculate the numbers of gamma delta T cells which have not the capacity to induce graphics host disease because they are actually a unrestricted and so for that reason, But they can fight viral infections. The advantage of this CD 34 selected transplant is also that you don't have to administer immunosuppressive therapy which everybody else needs to have in order to prevent graft versus host disease And still get a certain amount up to 60%. But that in itself requires a lot more patient care. These patients have to come to have their blood levels of immunosuppressive therapies monitored twice a week. At least. We don't need to do that. And that shortens the number of visits that shortens the side effect profile of the immune suppressive therapy and with that patients have a better quality of life. Okay, thank you. Doctor Kona for speaking with us, an incredible work you do here at Miami Cancer Institute. We are in fact thrilled that you've joined us a couple of years ago and sort of raised the level of care across the board. We're fortunate to have you on our team and we thank you for being with us today. Also want to thank all of you for listening. I really want this series to be useful and interesting for you, the people in the communities you've been part of us for a long time and if you have any questions on these topics, let us know we'd like to hear what you'd like to hear. So I'll see you again soon. Mike Synar signing off. Mm hmm, mm hmm hmm hmm hmm hmm hmm hmm.