Hi. My name is Francesca Cottini. I'm an assistant professor in the Division of hematology at the Ohio State University. Today I'm going to discuss one of my work, which focuses on real world data of monoclonal gammopathy of renal significance in the on novel therapy. So this work is a collaboration with the University of Chicago. And the last author of the paper is Doctor Matias Sanchez. So MGRS is which stands for monoclonal gammopathy or renal significance is, recently described entity characterized by the presence of a B-cell or a plasma cell clone which produce a natural toxic, immunoglobulins but does not meet criteria for other type of hematological malignancies, such as CLL or multiple myeloma or lymphoma. Usually these patients are not really responding to immunosuppressive therapies, in contrast with other type of glomerulonephritis. They tend to recur, unfortunately, after even a kidney transplant. And they also are at risk of developing, a type of hematological malignancies. Traditionally we have been starting to use clone directed therapies in these patients using, protosome inhibitors, Immunomodulatory drugs and more recently anti-CD38 monoclonal antibodies. In our studies, we are evaluating a cohort of 30 patients. And you need to keep in mind this is a pretty rare disease. So it's a good size cohort. Our patient which were diagnosed with MGRS between 2014 and 2024 at the Ohio State University, at the University of Illinois, Chicago, or at the stronger, larger hospital. These patients, had a median age of like 43. So relatively young patients, half of them were male and 80% of them were non-Hispanic white. By definition, most of them did not have a monoclonal protein in the blood or any abnormal free light chain ratio. But they had abnormal kidney function with elevated creatinine and also elevated proteinuria. That means they were, producing releasing a huge amount of proteins in their urine. of these patients were already on dialysis. It is a way that we do to replace the kidney function. And seven out of 30 of them at receive a kidney transplant in terms of like histopathological changes, by definition, we excluded all type of Al amyloidosis. And so most of the patients had what is called proliferative glomerulonephritis with monoclonal immune deposits, or other type, as defined by the International Kidney Working Group for MGRS. If we look at the type of treatment that they receive, like a quarter of them receive bortezomib based therapy with either just dexamethasone or cyclophosphamide, dexamethasone and bortezomib, half of them had daratumumab added to this regimen as some other patients, had different type of treatment, including immunosuppressive drugs or rituximab or, chemotherapy event. Half of these patients had autologous stem cell transplant as consolidation after the initial treatment. And, some of them also had the maintenance therapy or, a second line of therapy. The goal of our study was to see if these novel therapies or these therapy were helping the survival of these patients, and also the relapse free survival. That means being in remission without having the disease coming back. With a median follow up of 40 years, we saw that novel therapy are able to improve the overall survival of these patients. The five year old survival was, 84%, but unfortunately up to practically half of the patient by the 50 years they had a disease relapse. There were no differences in terms of overall survival or relapse free survival based on the type of therapy they received. But those patients who received some type for maintenance with either lenalidomide or monoclonal like anti-CD38 monoclonal antibody, had a longer overall survival. our data shows that definitely the use of the clone directed therapies is helping patients with MGRS even though there is still like a high rate of disease relapse. And the next step was really learning a little bit more about this pathology and potential identify novel target of novel therapy for these patients.
HealthTree • December 17, 2024