Dr. Carl June at the University of Pennsylvania has been working on the use of CAR T cells against blood cancers for over a decade. Work by him and his group is now bearing fruit. In a recently completed study, Dr. Adam Cohen and the team at UPENN targeted a protein not normally found on myeloma cells - CD19. The CD19 approach had been used with great results in CLL, non-Hodgkins Lymphoma and in ALL, with 80-90% response rates in ALL. Even though this target is not on the surface of most myeloma cells, they decided to try the therapy in myeloma in combination with autologous transplant. The rationale is that CAR T cells are very sensitive to even low levels of markers and that precursor myeloma cells could actually have CD19 on them. Another reason is that CD19 could actually act as an immunosuppressor, so by getting them out of the way, the treatment could do its job without the immune system kicking in to protect it. In their initial myeloma trial, the results for one high-risk patient (del17p. 1q gain and refractory to 9 prior therapies) were spectacular. She is still in complete remission over a year later. Normally, the longer the CAR T cells stick around in a patient (even 2-3 years later), the better the response. In the myeloma patients, they have not lasted as long, so Dr. Cohen describes how they are working on getting them to persist for a longer period of time. Dr. Cohen describes how they are now looking at varying the time frame in which they give the cells. They are now giving them 12-14 days after transplant. In other CAR T cell work, it could potentially be used without transplant, but because the CD19 is not normally present on myeloma cells, transplant had to be used to kill the myeloma tumor burden.  Their next target is CAR T cell treatment for BCMA because is it a safe target. Now, many other CAR T cell targets are being explored including CS1, BCMA, Kappa light chain and others. The prospects for this therapy are very exciting and Dr. Cohen and his team will continue their exciting work to make it even better over time. Clinical Trials Discussed in This Show BCMA CAR T Cells Without Transplant The Myeloma Crowd Radio Show With Dr. Adam Cohen