Treatment of B-cell Disorder Improves Renal Outcome of Patients With Monoclonal Gammopathy-Associated C3 Glomerulopathy

Blood. 2017 Mar 16;129(11):1437-1447. doi: 10.1182/blood-2016-08-737163. Epub 2017 Jan 9.

Abstract

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 MIg-associated 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 = .0001) and median renal survival (hazard ratio, 0.22; 95% confidence interval, 0.05-0.92; P = .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 survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / pathology*
  • Cohort Studies
  • Complement C3 / analysis*
  • Databases, Factual
  • Drug Therapy / methods
  • France
  • Humans
  • Kidney Diseases / drug therapy
  • Kidney Diseases / etiology*
  • Kidney Glomerulus / pathology
  • Middle Aged
  • Molecular Targeted Therapy
  • Paraproteinemias / complications*
  • Paraproteinemias / drug therapy*
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Complement C3