T Cell Redirection Therapy | Tarek Mouhieddine, MD | ASH 2022

My name is Tariq Mohideen and I'm a hematology oncology fellow at the Mount Sinai Hospital and my clinical and research interest is multiple myeloma. Right now we have been seeing a huge shift in the treatment of multiple myeloma over the past few years where immunotherapy has really changed the way we think about therapy for multiple myeloma and it has really changed clinical outcomes. Last year at ASH I presented an abstract about the ability of sequencing T cell redirection therapies. We showed a population of patients that we treated at our institution where we were able to continuously have deep and durable responses when we treat them with different bispecific antibodies or even CAR T cells targeting different antigens and this was basically the first proof that we can still reactivate the immune system and be able to control myeloma further even when you fail one T cell redirection therapy. So since then we have been trying to figure out the mechanism of resistance to different T cell redirection therapies as well as ways of overcoming them. So there are multiple studies right now or multiple groups that have been presenting some prelim data about CAR T cells as well as bispecific antibodies in terms of the changes in the immune microenvironment that happen but in our case we are doing a lot of immunophenotyping as well as studying clonal evolution in those patients that have been treated with sequential T cell redirection therapies and we have been trying to see if there is any new target or any differential immune phenotype that we can alter or we can target in order to overcome the resistance mechanisms that are stopping response against the T cell redirection therapies. So for example if we have a patient who is on a bispecific antibody we see a good response at first and then they eventually relapse or progress and we are looking at the immune microenvironment to see if this is related only to the T cells becoming exhausted and if they are presenting markers that we can target with current therapies like immune checkpoint inhibitors as well as immunomodulators and even using things like deratumumab or esatuximab so targeting CD38 as a mechanism or as a way of overcoming this mechanism. So we are doing that on over 100 patients and this is still a work in progress but hopefully it is going to give us a lot of answers soon and it is definitely going to help our patients and this way we will be able to keep patients in remission for a much longer period of time and hopefully at some point be able to achieve a cure.