Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease

• DOI: 10.1038/ki.2015.201
• Publication Date: 2015-07-15T15:41:31Z
• Authors: Camille Cohen; Bruno Royer; Vincent Javaugue; Raphael Szalat; Khalil El Karoui; Alexis Caulier; Bertrand Knebelmann; Arnaud Jaccard; Sylvie Chevret; Guy Touchard; Jean-Paul Fermand; Bertrand Arnulf; Frank Bridoux
• Keywords: Male; Middle Aged; Dexamethasone; 3. Good health; Bortezomib; Proteinuria; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Glomerular Basement Membrane; Disease Progression; Humans; Female; Immunoglobulin Light Chains; Kidney Diseases; Immunoglobulin Heavy Chains; Multiple Myeloma; Cyclophosphamide; Lenalidomide; Aged; Follow-Up Studies; Glomerular Filtration Rate; Retrospective Studies

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.