Outcomes in Monoclonal Gammopathy of Renal Significance with Novel Agents | Hira Shaikh and Mehndi Dandwani | #ASH24

Hi, my name is Mehendi Danwani. I'm one of the fellows at University of Iowa. I'm Dr. Hira Sheikh from the University of Iowa Hospital's faculty dealing with the plasma cell malignancies transplant and cellular therapy there. We are here to discuss about our study, which was role of novel treatments in monochronous gummopathy of renal significance. Now what does that mean is when there are certain clones of plasma cells from the bone marrow or B cell clones that produce an abnormal protein, which is different from monochronous gummopathy of undetermined significance as this causes secretion of proteins that cause kidney damage, which is proven upon kidney biopsy. And what we looked at is because there's a lack of scientific evidence in this area, we wanted to do a retrospective study to see what we found in terms of outcomes when we incorporated novel treatments like anti CD38 antibodies like daratumumab with or without autologous stem cell transplant, along with the traditional conservative regimen in terms of outcomes in this patient population. And what we found was that when we achieve a higher hematological response, what do we mean by hematological response? That means when we do bone marrow biopsy, there is in terms of stringent response would be no monoclonal plasma cells in the bone marrow and disappearance of these monoclonal proteins in urine and serum. That would be something that we look forward and we aim for. This should coincide with good renal responses because ultimately it is these light chains that are causing renal responses in this patient population. So what we found was when we achieved deeper hematological responses, these patients were less likely, about 93% less likely to need subsequent treatments when we treated them aggressively in the frontline regimen. Daratumumab, when it was used in frontline, what we saw was the time to next treatment was about 15 months compared to the traditional regimens that did not have daratumumab. Although this was not statistically significant because our patient population was very limited, 44 that was incorporated from five US centers. And what interestingly we found was that daratumumab based regimens in frontline had about stronger responses in terms of deeper hematological responses. And when immunomodulatory based regimens were used, they were less likely to show good responses. And this was statistically significant. So what we learned from this data is that we want to see, incorporate novel treatments and treat these patients aggressively so they don't have progression in their renal disease, which is the main aim that we are treating this patient population. MGRS is such a rare disease and it's dozens of, it's so heterogeneous, it's dozens of diseases in one class group. There is really no FDA approved treatment that unifies all of them. And a lot of these treatments are expanded or extrapolated from multiple myeloma, amyloidosis and so on. So it really becomes important to do these kind of studies and get some signals and look at what kind of therapies are going to be helpful, provide that data to our physicians and patients. So MGRS is when this clone, which was just hanging around, that could be MGUS or small ring myeloma, which are variations of the clone that has not become an active myeloma, that becomes active and it starts to attack the kidneys. It is unfortunately not identified until very late because there are not many symptoms related to the kidney disease failure. Many patients would present with lower extremity edema or edema or fluid overload all over the body. However, sometimes it could be just as subtle as the frothing of the urine because of a lot of protein being lost due to the subtypes of MGRS. There is, amyloidosis was sometimes considered to be MGRS, but now it's an own entity because it affects so many organs. I would say there are not great symptoms or signs, but I think something one could be looking for is frothing of urine, fluid overload, lower extremity swelling. I think the most important thing on the laboratory investigation is a proteinuria, especially looking for what is the component of albumin versus non-albumin. That is the only way we can identify it early. How Dr. Dhanwani said the ultimate goal is to prevent renal failure. We don't want these patients to be on dialysis or lose their kidneys. So we really want to try to do everything to save that. Immunomodulatory drugs, the most rampantly used is we know lenalidomide. This needs to be dose adjusted as per kidney function, first of all. So a lot of patients that we saw our median EGFR was somewhere around stage 3B kidney disease. So that limits us to using immunomodulatory drugs. And what our studies saw that even when we were exposing these patients, there were only 7% who had lenalidomide or other drug-based regimens that showed good response. So why expose our patients to the side effects of this drug? Yeah, I think that's, again, we are limited by our small data set, but these are some signals we are seeing and probably need to be further confirmed by multivariate analysis and larger disease, larger data groups.