Low-Dose Daratumumab for the Treatment of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits (PGNMID): A Case Report

Background: Proliferative glomerulonephritis with monoclonal immunoglobu- lin deposits (PGNMID) is an exceptionally rare glomerular disease, accounting for only 0.17–0.21% of all renal biopsies, with no consensus–based treatment algo- rithm established. Although daratumumab, a humanized anti–CD38 monoclonal antibody, has shown promising efficacy in PGNMID, the existing evidence base is confined to small case series employing standard–dose regimens (16 mg/kg). Crit- ically, data regarding reduced–dose daratumumab strategies for elderly patients with bortezomib–refractory disease and multiple comorbidities remain markedly limited. This case report documents a successful dose–reduction approach in a high–risk elderly patient, addressing a pivotal knowledge gap in the management of refractory PGNMID. Case presentation: A 73–year–old Chinese male with biopsy–proven PGNMID (IgG3– κ subtype) and chronic kidney disease stage 3b (baseline serum creatinine 1.5 mg/dL, proteinuria 5.61 g/24 h) with multiple comorbidities (hypertension, coronary artery disease, prior cerebral infarction) demonstrated treatment failure after four cycles of first–line CyBorD therapy (cyclophosphamide, bortezomib, dexamethasone). Post–treatment, he experienced progressive renal deterioration (serum creatinine elevation to 2.7 mg/dL), severe nephrotic–range proteinuria (10.61 g/24 h), hypoalbuminemia (22.8 g/L), and decompensated heart failure. Considering his advanced age and elevated infection susceptibility, a risk–adapted regimen comprising reduced–dose daratumumab (400 mg, 6 mg/kg; 37.5% of standard 16 mg/kg dosing) combined with bortezomib 2.2 mg was adminis- tered monthly over nine cycles. Following this nine–month treatment course, the patient attained partial renal remission, evidenced by substantial proteinuria reduction (to 1.12 g/24 h), serum albumin normalization (to 38.1 g/L), serum creatinine stabilization (at 1.6 mg/dL), negative immunofixation electrophore- sis conversion, and complete resolution of heart failure. Notably, no infectious complications were documented throughout the treatment period. Conclusions: This case provides proof–of–concept evidence that low–dose dara- tumumab combined with bortezomib constitutes a viable and well–tolerated salvage therapeutic option for elderly patients with bortezomib–refractory PGNMID and substantial comorbidity burden. The favorable clinical outcome achieved despite marked dose reduction (to 37.5% of standard dosing) suggests that adaptive dose–de–escalation strategies may preserve therapeutic efficacy while mitigating toxicity in high–risk patient populations. This report enriches the limited global evidence base for daratumumab application in PGNMID and underscores the imperative for investigation of personalized, risk–stratified dosing paradigms in managing this rare and therapeutically challenging glomerulopathy among vulnerable individuals.