title: Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease.
abstract: Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of plasma cell disorders, defined by linear Congo red-negative deposits of monoclonal light chain, heavy chain, or both along basement membranes. While renal involvement is prominent, treatment strategies, such as the impact of novel anti-myeloma agents, remain poorly defined. Here we retrospectively studied 49 patients with MIDD who received a median of 4.5 cycles of intravenous bortezomib plus dexamethasone. Of these, 25 received no additional treatment, 18 also received cyclophosphamide, while 6 also received thalidomide or lenalidomide. The hematological diagnoses identified 38 patients with monoclonal gammopathy of renal significance, 10 with symptomatic multiple myeloma, and 1 with Waldenstrom macroglobulinemia. The overall hematologic response rate, based on the difference between involved and uninvolved serum-free light chains (dFLCs), was 91%. After median follow-up of 54 months, 5 patients died and 10 had reached end-stage renal disease. Renal response was achieved in 26 patients, with a 35% increase in median eGFR and an 86% decrease in median 24-h proteinuria. Predictive factors were pre-treatment eGFR over 30 ml/min per 1.73 m(2) and post-treatment dFLC under 40 mg/l; the latter was the sole predictive factor of renal response by multivariable analysis. Thus, bortezomib-based therapy is a promising treatment strategy in MIDD, mainly when used early in the disease course. dFLC response is a favorable prognostic factor for renal survival.
authors.affiliation: Department of Nephrology, Necker Hospital, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Department of Hematology, CHU Amiens, Amiens, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.affiliation: Department of Nephrology, CHU Poitiers, Centre National de Référence Maladies Rares: Amylose AL et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Poitiers, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Javaugue
authors.affiliation: Department of Immunology and Hematology, Saint Louis Hospital, Paris, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Szalat
authors.affiliation: Department of Nephrology, Necker Hospital, Paris, France.
authors.forename: Khalil
authors.initials: K
authors.lastname: El Karoui
authors.affiliation: Department of Hematology, CHU Amiens, Amiens, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Caulier
authors.affiliation: Department of Nephrology, Necker Hospital, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Knebelmann
authors.affiliation: Department of Hematology, CHU Limoges, Centre National de Référence Maladies Rares: Amylose AL et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Limoges, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Jaccard
authors.affiliation: Department of Biostatistics and Informatics, Saint Louis Hospital, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevret
authors.affiliation: Department of Nephrology, CHU Poitiers, Centre National de Référence Maladies Rares: Amylose AL et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Poitiers, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Touchard
authors.affiliation: Department of Immunology and Hematology, Saint Louis Hospital, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Fermand
authors.affiliation: Department of Immunology and Hematology, Saint Louis Hospital, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnulf
authors.affiliation: Department of Nephrology, CHU Poitiers, Centre National de Référence Maladies Rares: Amylose AL et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Poitiers, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bridoux
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069286:Bortezomib / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D050533:Glomerular Basement Membrane / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D011507:Proteinuria / Q000188:drug therapy; D012189:Retrospective Studies; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D008258:Waldenstrom Macroglobulinemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*
chemical_list: D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide; D000077269:Lenalidomide