Effectiveness of Bortezomib in Cardiac AL Amyloidosis: A Report of Two Cases

Cardiac involvement is a major prognostic determinant in patients with primary AL amyloidosis. The clinical results of standard therapeutic approaches are suboptimal. It has been recently shown that bortezomib, an inhibitor of the proteasome, can induce rapid favourable responses in AL amyloidosis improving cardiac function and survival. Herein we report on two patients with cardiac amyloidosis treated by bortezomib who experienced partial or total remission of hematologic disease and of cardiac involvement. However, death of one patient, suffering from chronic kidney disease stage 5, due to fulminant respiratory syndrome suggests the need for caution in bortezomib use if patients have this comorbid condition. 1. Introduction Cardiac amyloidosis, which occurs as a complication of primary amyloidosis, is a result of cardiac deposition of insoluble, monoclonal immunoglobulin light chain fragments. This is observed in about 50% of patients with light chain amyloidosis predominantly after 40 years of age with higher prevalence in men than in women. The development of restrictive cardiomyopathy, complicated by progressive left ventricular or biventricular dysfunction, represents a major determinant of adverse outcome for these patients who typically die as a result of progressive heart failure or sudden cardiac death. A simple staging index for cardiomyopathy, based on levels of N-terminal brain natriuretic peptide (NTproBNP) and troponin I at presentation of disease, has been shown to predict median survival of 27.2, 11.1, and 4.1 months in stages I (normal values of both markers), II (altered values of only one marker), or III (altered values of both markers), respectively [1]. The aim of cardiac amyloidosis treatment is to reduce the concentration of the amyloidogenic light chains and to induce improvement of cardiac function and survival [2, 3] and it is crucial that treatment is rapidly effective, tolerable, and safe. The severity of cardiac involvement and the high toxicity treatment profile, however, have always limited the outcome of traditional treatment options based on high dose melphalan chemotherapy followed by autologous stem cell transplantation. Recently it has been shown that bortezomib, a proteasome inhibitor, can induce rapid responses in AL amyloidosis improving cardiac function and survival [4]. We report herein two cases of cardiac amyloidosis in which treatment with bortezomib was associated with partial or complete clinical remission of disease. 2. Case Presentation 2.1. Case Report 1 A 54-year-old man was referred to our institution