Reduced-dose daratumumab and bortezomib may achieve partial renal remission in CyBorD-refractory PGNMIDReduced Dose Daratumumab Shows Promise for Rare Kidney Disease

BackgroundProliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is an exceptionally rare glomerular disease, accounting for only 0.17–3.7% of all renal biopsies, and no consensus–based treatment algo-rithm has been established. Although daratumumab, a humanized anti-CD38 monoclonal antibody, has shown promising efficacy in PGNMID, the existing evidence is limited to small case series using standard-dose regimens (16 mg/kg). Critically, data on reduced-dose daratumumab in elderly patients with CyBorD-refractory disease and multiple comorbidities remain scarce. This case report adds to the limited experience with a reduced-dose strategy in a high-risk elderly patient with CyBorD-refractory PGNMID.Case presentationA 73-year-old Chinese male with biopsy-proven PGNMID (IgG3-κ subtype), chronic kidney disease stage 3a, a baseline serum creatinine 1.5 mg/dL (132.6 μmol/L), proteinuria 5.61 g/24 h, and multiple comorbidities (hypertension, coronary artery disease, and prior cerebral infarction) received first-line CyBorD therapy (cyclophosphamide, bortezomib, and dexamethasone). After four cycles, he demonstrated treatment failure. He subsequently developed progressive renal deterioration [serum creatinine 2.7 mg/dL (239 μmol/L)], severe nephrotic-range proteinuria (10.61 g/24 h), hypoalbuminemia (22.8 g/L), and decompensated heart failure. Given his advanced age and high infection risk, a risk-adapted regimen was administered monthly for 12 cycles: reduced-dose daratumumab (400 mg, ∼6 mg/kg, 37.5% of the standard 16 mg/kg dose) combined with bortezomib 2.2 mg. After 12 months, the patient achieved partial renal remission: proteinuria decreased to 1.12 g/24 h, serum albumin normalized to 38.1 g/L, serum creatinine stabilized at 1.6 mg/dL (141.4 μmol/L), immunofixation electrophoresis converted to negative, and clinical resolution of heart failure was achieved. Notably, no infectious complications were documented throughout the treatment period.ConclusionThis case suggests that low-dose daratumumab combined with bortezomib may be a feasible and apparently well-tolerated salvage option in this selected patient with CyBorD-refractory PGNMID and a heavy comorbidity burden. The favourable outcome in this single case raises the possibility that dose de-escalation might preserve efficacy while mitigating toxicity, although this hypothesis requires confirmation in larger studies. This report adds to the limited global evidence for daratumumab in PGNMID and highlights the need for personalized, risk-stratified dosing strategies in this rare and challenging glomerulopathy.