A single-arm, open-label trial to evaluate the efficacy and safety of reduced-dose daratumumab in combination with bortezomib and dexamethasone (DVd-lite) in patients with newly diagnosed monoclonal gammopathy of renal significance (MGRS)

Abstract Background: Clone-directed therapy is essential for managing monoclonal gammopathy of renal significance (MGRS), as it reduces nephrotoxic monoclonal protein burden and preserves renal function. Now, available literature on treatment strategies and clinical outcomes remains limited. Method: This open-label, prospective clinical trial assessed the efficacy of a combination of reduced-dose daratumumab (Dara), bortezomib and dexamethasone (DVd-lite) on newly diagnosed MGRS patients. Between February 2024 and August 2025, a total of 10 patients (age range: 46-70 years, median age: 52 years, seven male) were enrolled. The treatment protocol consisted of six cycles of the DVd-lite regimen compromising Dara (8-10 mg biweekly), bortezomib (1.3 mg/m2 weekly) and dexamethasone (5-20 mg weekly). Results: Among the 10 evaluable patients, the median follow-up duration of this cohort was 12.7 months (range: 4.4-17.3 months). The results showed that the hematological overall response rate (ORR) was 80% (8/10) and the kidney ORR was 90% (9/10). Moreover, the complete response rate in both hematology and kidneys were 60% (6/10). Only one patient experienced a grade 3 treatment-related adverse events, which was bronchospasm caused by Dara's first infusion. Conclusions: These findings demonstrated that the DVd-lite regimen is an effective and well-tolerated first-line treatment option for newly diagnosed MGRS patients.