Maintenance therapy and improved relapse-free survival in patients with monoclonal gammopathy of renal significance

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity with multiple therapeutic approaches, often modeled after therapies used for multiple myeloma, including anti-CD38 antibodies, proteasome inhibitors, immunomodulatory agents, and autologous stem cell transplantation (ASCT). However, because of its rarity, the optimal use of newer agents, ASCT, and maintenance therapy remains poorly defined. We retrospectively analyzed 50 patients with biopsy-proven MGRS treated across 3 institutions. The most common histopathologic diagnosis was proliferative glomerulonephritis with monoclonal immunoglobulin deposits (72%). Median estimated glomerular filtration rate was 32 mL/min (interquartile range, 17-51), and median 24-hour proteinuria was 3.28 g. A total of 37 patients received plasma cell (PC)-directed therapy, and 8 patients received B-cell-directed therapy. Common PC-directed induction regimens included daratumumab-based therapy (32.4%), CyBorD (cyclophosphamide, bortezomib, and dexamethasone; 29.7%), and bortezomib-dexamethasone (29.7%). Maintenance therapy was administered to 13 of 37 treated patients in the PC group (35.1%). With a median follow-up of 6.15 years, the median relapse-free survival (RFS) was 3.74 years in the PC group and 19 years in the B-cell group. Among PC-treated patients, RFS and overall survival (OS) did not significantly differ by induction regimen or use of ASCT. In contrast, maintenance therapy and induction duration >6 months were associated with significantly improved RFS, which remained significant on multivariate analysis. These findings suggest that maintenance therapy and prolonged treatment duration may improve disease control in MGRS and support further evaluation of extended treatment strategies to prevent renal damage and improve long-term outcomes.