Chemotherapy for renal AL amyloidosis: treatment results and outcomes in 49 patients from a single center

Introduction AL amyloidosis is actually known to be the most common form of systemic amyloidosis in the Western countries [1, 2]. In this particular type of amyloidosis monoclonal immunoglobulin light chains, produced by plasma cell clone, undergo aggregation and form amyloid deposits, almost always systemically, and kidneys are one of the most frequent sites of amyloid deposition [3, 4, 5]. AL amyloidosis may occur in some patients with overt multiple myeloma, and rarely arise in association with Waldenström macroglobulinemia and nonHodjkin lymphoma/leukaemia, but usually the degree of plasma cell proliferation in AL amyloidosis is low or even undetectable, thus for many years it used to be named “primary” amyloidosis, the term which is actually eliminated [6, 7, 8, 9, 10, 11, 12, 13]. Despite its non-malignant nature, so-called “primary” AL amyloidosis is associated with a high morbidity and mortality. In 2012 the term “monoclonal gammopathy of renal significance” (MGRS) was proposed by International Kidney and Monoclonal Gammopathy Research Group (IKMGRG) in order to stress the target-organ damage crucial significance in the group of “dangerous small B-cell clones”-driven diseases (AL amyloidosis, light/heavy chain deposition disease, proliferative glomerulonephritis with monoclonal immunoglobulin deposits, immunotactoid glomerulonephritis), and discriminate them from “monoclonal gammopathy of undetermined significance” [3, 14, 15, 16]. AL amyloidosis is actually known to be the most common form of systemic amyloidosis. Renal involvement is characteristic for AL amyloidosis and almost invariably results in proteinuria, more that 50% of patients present with nephrotic syndrome at diagnosis, about 20% of patients require dialysis over time. Beyond kidneys, the other most affected by AL amyloidosis organ is heart; other sites of damage include liver, peripheral and autonomous nervous system and soft tissues. Historically, combination of melphalan and prednisone was used for AL amyloidosis treatment, later combination of melphalan and dexamethasone and high dose melphalan with autologous stem cell transplantation were introduced, and recently regimens, including bortezomib-dexamethasone, cyclophosphamide-bortezomib-dexamethasone and others were adopted from multiple myeloma treatment protocols. Treatment outcomes depend on severity of renal and cardiac involvement. In our retrospective study we aimed to evaluate treatment efficacy and long-term outcomes in 49 patients with biopsyproven AL amyloidosis, treated in our unit with above mentioned chemotherapy regimens over last 15 years. At the time of kidney biopsy 81% of patients had nephrotic syndrome, 43% had impaired kidney function, and 30% presented with both nephrotic syndrome and renal dysfunction. In one third of patient’s population kidneys were the only site of damage, others presented with kidneys and heart or multiorgan involvement. Under chemotherapy 42.8% of patients achieved hematological remission, and 34.6% both haematological and organ remission. The rate of hematological remissions was significantly higher those who received autologous stem cell transplantation. During follow-up period 12 [4; 29] months 14% of patients started dialysis and 41% died. 5-year cumulative survival reached 50% in patients, treated with bortezomib, in melphalan-based treatment subgroups and it was only 29-21-30%, however the differences were not significant. Bortezomib-based regimens also showed the tendency to better 5-year patients (69% vs 29-29-30%), but not kidney (72% vs 100-49-100%) survival.