High Dose Chemotherapy and Autologous Stem Cell Transplantation with Melphalan in Patients with Monoclonal Immunoglobulin Deposition Disease Associated with Multiple Myeloma.
Authors: Hassoun Hani , Rafferty Brian T. , Flombaum Carlos , D’Agati Vivette D. , Klimek Virginia M. , Cohen Adam , Boruchov Adam , Kewalramani Tarun , Reich Lilian , Landau Heather , Nimer Stephen D. , Comenzo Raymond 
Published: October 2019

Abstract
Introduction: Monoclonal immunoglobulin deposition disease (MIDD) includes several disorders that are characterized by the deposition of serum monoclonal gamma-globulins in various organs, most notably in the kidney resulting in renal dysfunction. There is no standard therapy for MIDD. We report our experience with high dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC/ASCT) in patients with MIDD associated with underlying multiple myeloma (MM).
Methods: We have done a retrospective analysis of patients seen at MSKCC with biopsy proven MIDD associated with MM and who underwent HDC/ASCT between 2002 and 2007.
Results: Seven patients, all male with a median age of 46, had MM and MIDD. Five had Light Chain Deposition Disease (LCDD), 1 Light and Heavy Chain Deposition Disease (LHCDD), and 1 Light Chain Crystal Deposition Disease (LCCDD). All were stage IB by Durie-Salmon classification. Bone marrow plasmacytosis was a median of 21% (range 10 to 41%). Serum immunofixation showed an IgG kappa monoclonal band in only 2 patients while serum protein electrophoresis showed a monoclonal spike in only 1 of the 2. A monoclonal kappa light chain was detected by serum Free Light Chain Assay in all 7 patients. The diagnosis of MIDD was confirmed by immunofluorescence staining and electron-microscopy examination of kidney biopsy specimens in all patients. Three patients were dialysis dependent before HDC/ASCT. All patients received Melphalan 140 mg/m2 followed by peripheral blood stem cell rescue. The treatment was well tolerated with no mortality and no unexpected morbidity. This treatment modality was effective in controlling the underlying plasma cell dyscrasia and light chain production as six patients achieved complete hematologic remission (CR, by EORTC criteria) post-transplantation and remain in CR after a median follow up of 18.6 months (2.9 to 64.8 months). One patient achieved partial remission (PR). The median progression free survival has not been reached but the patient with a PR had progression of his MM and is currently receiving second-line therapy. Among the 4 patients who were dialysis independent at the time of HDC/ASCT, the renal function has improved compared to pre-HDC/ASCT in 2, remained stable in 1 (who achieved hematologic PR), and worsened in 1 leading to hemodialysis despite hematologic CR. Among the three patients who were dependent on hemodialysis at the time of HDC/ASCT, 2 have undergone kidney transplantation 14.1 and 45.7 months after HDC/ASCT and have a normal creatinine clearance 30.9 and 64.8 months after HDC/ASCT, respectively. The third patient remains in hematologic CR but has resumed peritoneal dialysis after a two-month-period of dialysis independence post-HDC/ASCT. He is currently being evaluated for kidney transplantation.
Conclusions: Our results corroborate previous encouraging but limited experience with HDC/ASCT in MIDD and compare favorably with historical reports of conventional therapy in this patient population. These results also argue in favor of kidney transplantation in patients who achieve a hematologic CR after HDC/ASCT for MM associated with MIDD.