ASH 2024 | Outcomes for patients with MGRS receiving modern multiple myeloma therapies

So our group developed an interest in monoclonal gammopathy of renal significance a number of years ago and we’ve been collecting data both retrospectively and prospectively for patients with that heterogeneous family of disorders and our interest was in determining how these patients respond to more modern treatments that have been developed for multiple myeloma and other plasma cell disorders. So we evaluated patients who were treated at our institution between 2016 and 2023 and who received modern regimens that would be used for multiple myeloma. There were 31 patients in this data set and about half of them had what is called PGNMID or proliferative glomerulonephritis with monoclonal immune deposits. The rest of the patients had other types of monoclonal gammopathy of renal significance. We excluded amyloidosis because there’s a well-established treatment paradigm for amyloidosis and we wanted to evaluate how patients with the non-amyloid or the rarer subtypes did on treatment. What we discovered, and the endpoints of our study, by the way, were renal progression-free survival. So our primary objective was to evaluate how patients did in terms of renal progression. What we found was that the majority of patients, 77% of patients, had a renal response when treated with a modern myeloma therapy, and 85% of patients had a hematologic response, at least 85% of those who were evaluable. Renal progression-free survival at a median follow-up of 29 months was 77%. However, survival was particularly poor in patients who presented with proteinuria, a level of proteinuria over three and a half grams daily, or those who presented with a histologic subtype that included PGNMID. So this study helped us identify two subgroups of patients within the umbrella of monoclonal gammopathy of renal significance that may perform more poorly with modern myeloma therapies. In terms of the therapies people received, approximately 80% received a bortezomib-based regimen, 40% received daratumumab, and about 50% received alkylating agents in various combinations. 7% of patients in the study underwent autologous stem cell transplantation. And the emphasis here and the takeaway message here is that there is a lot of heterogeneity both in how the disorder presents, the prognosis, how patients respond, and also the way that patients are treated with this widely available array of modern therapies. Our goals for the future are to use this data and use data from collaborating institutions to help establish a more uniform treatment paradigm to assist clinicians in helping to treat patients with this rare disease.

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