Bortezomib-Cyclophosphamide-Dexamethasone versus Rituximab in PGNMID

Background

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare renal disorder for which prospective controlled treatment evidence is limited. Clone-directed therapies targeting plasma cells or B cells are increasingly used, but comparative prospective data are lacking.

Methods

This single-center, open-label, pilot RCT aimed to evaluate the feasibility and preliminary efficacy of plasma cell-targeted therapy (bortezomib-cyclophosphamide-dexamethasone, BCD) versus B-cell-targeted therapy (rituximab, RTX). Twenty eligible patients were randomized (1:1) to receive either 6 cycles of BCD or 4 weekly doses of rituximab at375 mg/m². In patients with B-cell reconstitution > 5/μL, a 500 mg rituximab booster dose was administered at 6 months according to the prespecified protocol. The primary efficacy endpoint was overall renal response at 12 months. Changes in proteinuria, serum albumin and estimated glomerular filtration rate were also assessed at 6 and 12 months as secondary outcomes. Safety outcomes included infections and hematologic toxicity.

Results

Baseline characteristics were generally comparable between groups. The median age was 57 years, and mean proteinuria 4.1 ± 3.1 g/d. In the primary intention-to-treat analysis (n = 20), the primary outcome of overall renal response at 12 months was observed in 60% (6/10) of patients in the BCD group and 70% (7/10) in the RTX group (P = 1.0). Treatment failure occurred in 2 patients in the BCD group and none in the RTX group. At 6 months, complete response occurred in five patients in the BCD group and three patients in the RTX group. Both groups showed reductions in proteinuria and improvements in serum albumin over 12 months. A transient decline in estimated glomerular filtration rate was observed in the BCD group at 6 months and recovered by 12 months. Safety profiles were manageable, with one serious adverse event, pneumonia, in the BCD group.

Conclusion

Both BCD and rituximab were associated with renal responses in this exploratory pilot trial of PGNMID. Given the small sample size, open-label design, and differences in treatment exposure structure, these findings are hypothesis-generating. Larger multicenter studies with longer follow-up are needed to define optimal therapy for PGNMID.

Trial registration: chictr.org.cn Identifier: ChiCTR2500102928