Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy

Abstract

Key Points• Monoclonal gammopathy is associated with C3 glomerulopathy.• Specific treatment of the underlying B-cell clone improves renal survival.The high frequency of monoclonal gammopathy in adult patients with C3 glomerulopathy (C3G) emphasizes the role of monoclonal immunoglobulin (MIg) in the occurrence of renal disease and raises the issue of the therapeutic management. The aim of the study was to evaluate the effect of chemotherapy in a large cohort of patients with MIgassociated C3G. Fifty adult patients with MIg and biopsy-proven C3G were extracted from the French national database of C3G. We retrospectively compared renal outcomes in patients who either received or did not receive chemotherapy targeting the underlying B-cell clone. At diagnosis, renal disease was severe, with nephrotic-range proteinuria in 20/46 (43%) patients and chronic kidney disease stage 3 or above in 42/49 (86%) patients. Monoclonal gammopathy was of IgG type in 47 (94%) patients. Hematological diagnosis was monoclonal gammopathy of renal significance in 30 (60%), multiple myeloma in 17 (34%), and chronic lymphocytic leukemia in 3 (6%) patients. Complement studies showed low C3 level in 22/50 (43%) and elevated soluble C5b-9 level in 27/34 (79%) patients. Twenty-nine patients received chemotherapy (including bortezomib in 22), whereas 8 and 13 patients received various immunosuppressive drugs or symptomatic measures alone, respectively. Patients who achieved hematological response after chemotherapy had higher renal response rates (P 5 .0001) and median renal survival (hazard ratio, 0.22; 95% confidence interval, 0.05-0.92; P 5 .009) than those receiving conservative/immunosuppressive therapy. In conclusion, our results suggest that chemotherapy adapted to the B-cell clone may constitute an efficient strategy for C3G in the setting of MIg, as rapid achievement of hematological response appears to result in improved renal

Plasma cell diseases and organ transplant: A comprehensive review

“…published retrospective analysis of 50 adult patients in France with monoclonal gammopathy and biopsy-proven C3G, some benefit of treatment of the underlying plasma cell dyscrasia, with improvement in renal disease, was noted 57. In this series, most had severe renal disease, with 42 of 49 having stage 3-4 chronic kidney disease, and 47 of 49 having monoclonal gammopathy.…”

Dysproteinemias and Glomerular Disease

“…In multiple myeloma, it is confirmed by a negative bone marrow biopsy. More recently, achievement of VGPR or better was found to be effective at preventing the development of ESRD in patients with C3 glomerulopathy with monoclonal gammopathy (76). In this study, 76% of the patients used a bortezomib-based regimen, whereas 7% used a rituximab-based chemotherapy.…”

“…Traditional immunosuppressive drugs and renin-angiotensin system blockade are generally ineffective at preventing ESRD (76). Clone-directed therapy is the key.…”

Treatment with bortezomib in dense deposit disease associated with monoclonal gammopathy of undetermined significance

“…Chemotherapy with bortezomib in monoclonal immunoglobulin deposit disease (MIDD) seems to improve renal function and decrease the risk of developing ESRD (Cohen et al , ; Chauvet et al , ) To the best of our knowledge, this is the first case of DDD with MGUS to be treated with bortezomib, which demonstrated improvement of renal disease after 8 cycles. This would reinforce the role of MGUS in the pathogenesis of DDD.…”