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

Sophie Chauvet (1) , Veronique Fremeaux-Bacchi (2) , Florent Petitprez (3) , Alexandre Karras (4) , Laurent Daniel (5) , Stéphane Burtey (6) , Gabriel Choukroun (7) , Yahsou Delmas (8) , Dominique Guerrot (9) , Arnaud François (10) , Moglie Le Quintrec (11) , Vincent Javaugue (12) , David Ribes , Laurence Vrigneaud (13) , Bertrand Arnulf (14) , Jean Michel Goujon (15, 12) , Pierre Ronco (16) , Guy Touchard (17, 12) , Frank Bridoux (17, 12)

1 IBDM - Institut de Biologie du Développement de Marseille
2 Laboratoire d'Immunologie Biologique
3 CRC - Centre de Recherche des Cordeliers
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
6 VRCM - Vascular research center of Marseille
7 Unité de Soins Intensifs Médicaux
8 Service de Néphrologie-transplantation-dialyse [Bordeaux]
9 Service de Néphrologie [Rouen]
10 Service d'Anatomie et Cytologie Pathologique [CHU Rouen]
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales
13 Service de Néphrologie [Valenciennes]
14 Service d'hématologie biologique
15 Service d'Anatomie et de Cytologie Pathologiques [Poitiers]
16 Remodelage et Reparation du Tissu Renal
17 CHU Poitiers - Centre hospitalier universitaire de Poitiers

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.

Domains: Life Sciences [q-bio]; Human health and pathology; Hematology; Life Sciences [q-bio]; Human health and pathology; Urology and Nephrology

Sophie Chauvet, Veronique Fremeaux-Bacchi, Florent Petitprez, Alexandre Karras, Laurent Daniel, et al.. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy. Blood, 2017, 129 (11), pp.1437-1447. ⟨10.1182/blood-2016-08-737163⟩. ⟨hal-01790090⟩