In our second MCRI episode featuring the top 10 proposals for high-risk multiple myeloma, Dr. Guenther Koehne explains a truly extraordinary approach for highly relapsed/refractory and plasma cell leukemia patients. First, he uses T-cell depleted allogeneic transplants to eliminate the dreaded graft vs. host side effects that are typical of allo transplant. He describes how they remove the T cells from the donors cells before infusing them into the patient. It was believed that a small level of graft vs. host was needed for good response to allo transplant, but he tells us that the data may indicate that graft vs. host may not be necessary for an anti-myeloma affect. Next, he has identified a tumor receptor called WT1 expressed on most myeloma cells from his work in leukemia. He can engineer the T cells to find that receptor and initiate cell death without side effects that are commonly found in CAR T cell approaches. As a third step, he is now working increase the effectivity by training those WT1 cells to secret Interleukin 12. IL-12 enhances the survival of these T cells and acts as a "homing" device to help the T cells find the WT1 signal, rounding up the cells that need to be eliminated. His results are truly outstanding. In his second clinical trial that included both relapsed/refractory myeloma and plasma cell leukemia patients, there are zero reported cases of graft vs. host disease and many in the trial (even those with plasma cell leukemia) are now in complete remission. This is truly remarkable because those with PCL have very poor outcomes. He is now opening up a third trial to continue this impressive work. The Myeloma Crowd Radio Show with Dr. Guenther Koehne, MD, PhD.