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 transplant (ASCT). However, due to 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 three institutions. The most common histopathology was proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID, 72%). Median estimated glomerular filtration rate (eGFR) was 32 mL/min (IQR: 17-51), and median 24-hour proteinuria was 3.28 g. Thirty-seven patients received plasma cell (PC)-directed therapy and eight patients received B-cell-directed therapy. Common PC-directed induction regimens included daratumumab-based therapy (32.4%), cyclophosphamide-bortezomib-dexamethasone (CyBorD) (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, 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 longer than six months were associated with significantly improved RFS, which remained significant in the 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.